Key clinical point: Lapatinib demonstrated excellent survival outcomes in patients with small, node-negative, human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC), when used in combination with trastuzumab, but not when used as a substitute for trastuzumab.

Major finding: The 7-year disease-free survival (DFS) rate in the overall cohort was excellent (88.1%), with improved DFS outcomes observed in the trastuzumab (89.6%), trastuzumab followed by lapatinib (89.0%), and trastuzumab+lapatinib (89.1%) arms, but not as much in the lapatinib-only arm (84.3%; stratified log-rank P   =   .031).

Study details: Findings are from a subanalysis of the phase 3 ALTTO trial including 2821 patients with small (pathological tumor size ≤ 3 cm), lymph node-negative, early HER2+ BC who were randomly assigned to receive adjuvant therapy with trastuzumab, lapatinib, trastuzumab followed by lapatinib, or trastuzumab+lapatinib.

Disclosures: The ALTTO trial received funding from GlaxoSmithKline, Novartis Pharma AG, and other sources. Two authors declared being employees of and owning stocks in Novartis. The other authors reported ties with several sources, including Novartis.

Source: Nader-Marta G et al. Outcomes of patients with small and node-negative HER2-positive early breast cancer treated with adjuvant chemotherapy and anti-HER2 therapy-a sub-analysis of the ALTTO study. Br J Cancer. 2022 (Sep 1). Doi: 10.1038/s41416-022-01963-8

Key clinical point: Lapatinib demonstrated excellent survival outcomes in patients with small, node-negative, human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC), when used in combination with trastuzumab, but not when used as a substitute for trastuzumab.

Major finding: The 7-year disease-free survival (DFS) rate in the overall cohort was excellent (88.1%), with improved DFS outcomes observed in the trastuzumab (89.6%), trastuzumab followed by lapatinib (89.0%), and trastuzumab+lapatinib (89.1%) arms, but not as much in the lapatinib-only arm (84.3%; stratified log-rank P   =   .031).

Study details: Findings are from a subanalysis of the phase 3 ALTTO trial including 2821 patients with small (pathological tumor size ≤ 3 cm), lymph node-negative, early HER2+ BC who were randomly assigned to receive adjuvant therapy with trastuzumab, lapatinib, trastuzumab followed by lapatinib, or trastuzumab+lapatinib.

Disclosures: The ALTTO trial received funding from GlaxoSmithKline, Novartis Pharma AG, and other sources. Two authors declared being employees of and owning stocks in Novartis. The other authors reported ties with several sources, including Novartis.

Source: Nader-Marta G et al. Outcomes of patients with small and node-negative HER2-positive early breast cancer treated with adjuvant chemotherapy and anti-HER2 therapy-a sub-analysis of the ALTTO study. Br J Cancer. 2022 (Sep 1). Doi: 10.1038/s41416-022-01963-8

Key clinical point: Lapatinib demonstrated excellent survival outcomes in patients with small, node-negative, human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC), when used in combination with trastuzumab, but not when used as a substitute for trastuzumab.

Major finding: The 7-year disease-free survival (DFS) rate in the overall cohort was excellent (88.1%), with improved DFS outcomes observed in the trastuzumab (89.6%), trastuzumab followed by lapatinib (89.0%), and trastuzumab+lapatinib (89.1%) arms, but not as much in the lapatinib-only arm (84.3%; stratified log-rank P   =   .031).

Study details: Findings are from a subanalysis of the phase 3 ALTTO trial including 2821 patients with small (pathological tumor size ≤ 3 cm), lymph node-negative, early HER2+ BC who were randomly assigned to receive adjuvant therapy with trastuzumab, lapatinib, trastuzumab followed by lapatinib, or trastuzumab+lapatinib.

Disclosures: The ALTTO trial received funding from GlaxoSmithKline, Novartis Pharma AG, and other sources. Two authors declared being employees of and owning stocks in Novartis. The other authors reported ties with several sources, including Novartis.

Source: Nader-Marta G et al. Outcomes of patients with small and node-negative HER2-positive early breast cancer treated with adjuvant chemotherapy and anti-HER2 therapy-a sub-analysis of the ALTTO study. Br J Cancer. 2022 (Sep 1). Doi: 10.1038/s41416-022-01963-8

Key clinical point: Neratinib as monotherapy or in combination with capecitabine showed good survival outcomes and was well tolerated in a real-world setting of patients with advanced human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) with or without brain metastases (BM).

Major finding: The median progression-free survival (PFS) and overall survival (OS) for all patients were 5.9 months (95% CI 4.9-7.4) and 15.0 months (95% CI 10.4-22.2), respectively, with survival outcomes being similar in patients with vs without BM. PFS and OS were significantly longer with neratinib+capecitabine vs neratinib (P ≤ .001). Diarrhea was the major adverse event (64%) with 10% being grade 3.

Study details: Findings are from a single-center retrospective study including 72 patients with advanced HER2+ BC who received neratinib (n = 27) or neratinib+capecitabine (n = 45). Thirty-eight patients had BM.

Disclosures: This study was supported by the Royal Marsden National Institute for Health and Care Research Biomedical Research Centre for Cancer, UK. The authors declared receiving research funding, speaker’s fees, honoraria, or travel support from several sources.

Source: Cunningham N et al. Neratinib in advanced HER2-positive breast cancer: Experience from the Royal Marsden Hospital. Breast Cancer Res Treat. 2022;195(3):333-340 (Aug 17). Doi: 10.1007/s10549-022-06703-3

Key clinical point: Neratinib as monotherapy or in combination with capecitabine showed good survival outcomes and was well tolerated in a real-world setting of patients with advanced human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) with or without brain metastases (BM).

Major finding: The median progression-free survival (PFS) and overall survival (OS) for all patients were 5.9 months (95% CI 4.9-7.4) and 15.0 months (95% CI 10.4-22.2), respectively, with survival outcomes being similar in patients with vs without BM. PFS and OS were significantly longer with neratinib+capecitabine vs neratinib (P ≤ .001). Diarrhea was the major adverse event (64%) with 10% being grade 3.

Study details: Findings are from a single-center retrospective study including 72 patients with advanced HER2+ BC who received neratinib (n = 27) or neratinib+capecitabine (n = 45). Thirty-eight patients had BM.

Disclosures: This study was supported by the Royal Marsden National Institute for Health and Care Research Biomedical Research Centre for Cancer, UK. The authors declared receiving research funding, speaker’s fees, honoraria, or travel support from several sources.

Source: Cunningham N et al. Neratinib in advanced HER2-positive breast cancer: Experience from the Royal Marsden Hospital. Breast Cancer Res Treat. 2022;195(3):333-340 (Aug 17). Doi: 10.1007/s10549-022-06703-3

Key clinical point: Neratinib as monotherapy or in combination with capecitabine showed good survival outcomes and was well tolerated in a real-world setting of patients with advanced human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) with or without brain metastases (BM).

Major finding: The median progression-free survival (PFS) and overall survival (OS) for all patients were 5.9 months (95% CI 4.9-7.4) and 15.0 months (95% CI 10.4-22.2), respectively, with survival outcomes being similar in patients with vs without BM. PFS and OS were significantly longer with neratinib+capecitabine vs neratinib (P ≤ .001). Diarrhea was the major adverse event (64%) with 10% being grade 3.

Study details: Findings are from a single-center retrospective study including 72 patients with advanced HER2+ BC who received neratinib (n = 27) or neratinib+capecitabine (n = 45). Thirty-eight patients had BM.

Disclosures: This study was supported by the Royal Marsden National Institute for Health and Care Research Biomedical Research Centre for Cancer, UK. The authors declared receiving research funding, speaker’s fees, honoraria, or travel support from several sources.

Source: Cunningham N et al. Neratinib in advanced HER2-positive breast cancer: Experience from the Royal Marsden Hospital. Breast Cancer Res Treat. 2022;195(3):333-340 (Aug 17). Doi: 10.1007/s10549-022-06703-3

Key clinical point: Addition of durvalumab to neoadjuvant chemotherapy (NACT) improved survival in women with early triple-negative breast cancer (TNBC) although improvement in the pathological complete response (pCR) rate was nonsignificant.

Major finding: In the overall cohort, durvalumab vs placebo improved 3-year invasive disease-free survival (hazard ratio [HR] 0.48; log-rank P   =   .036), distant disease-free survival (HR 0.31; log-rank P   =   .005), and overall survival (HR 0.24; log-rank P   =   .006) rates, despite no adjuvant component of durvalumab.

Study details: Findings are from the phase 2 GeparNuevo study including 174 patients with primary nonmetastatic TNBC who were randomly assigned to receive NACT with durvalumab or placebo.

Disclosures: This study was funded by AstraZeneca and Celgene. The authors declared receiving grants, personal fees, nonfinancial support, or other support from several sources.

Source: Loibl S et al. Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann Oncol. 2022 (Aug 9). Doi: 10.1016/j.annonc.2022.07.1940

Key clinical point: Addition of durvalumab to neoadjuvant chemotherapy (NACT) improved survival in women with early triple-negative breast cancer (TNBC) although improvement in the pathological complete response (pCR) rate was nonsignificant.

Major finding: In the overall cohort, durvalumab vs placebo improved 3-year invasive disease-free survival (hazard ratio [HR] 0.48; log-rank P   =   .036), distant disease-free survival (HR 0.31; log-rank P   =   .005), and overall survival (HR 0.24; log-rank P   =   .006) rates, despite no adjuvant component of durvalumab.

Study details: Findings are from the phase 2 GeparNuevo study including 174 patients with primary nonmetastatic TNBC who were randomly assigned to receive NACT with durvalumab or placebo.

Disclosures: This study was funded by AstraZeneca and Celgene. The authors declared receiving grants, personal fees, nonfinancial support, or other support from several sources.

Source: Loibl S et al. Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann Oncol. 2022 (Aug 9). Doi: 10.1016/j.annonc.2022.07.1940

Key clinical point: Addition of durvalumab to neoadjuvant chemotherapy (NACT) improved survival in women with early triple-negative breast cancer (TNBC) although improvement in the pathological complete response (pCR) rate was nonsignificant.

Major finding: In the overall cohort, durvalumab vs placebo improved 3-year invasive disease-free survival (hazard ratio [HR] 0.48; log-rank P   =   .036), distant disease-free survival (HR 0.31; log-rank P   =   .005), and overall survival (HR 0.24; log-rank P   =   .006) rates, despite no adjuvant component of durvalumab.

Study details: Findings are from the phase 2 GeparNuevo study including 174 patients with primary nonmetastatic TNBC who were randomly assigned to receive NACT with durvalumab or placebo.

Disclosures: This study was funded by AstraZeneca and Celgene. The authors declared receiving grants, personal fees, nonfinancial support, or other support from several sources.

Source: Loibl S et al. Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann Oncol. 2022 (Aug 9). Doi: 10.1016/j.annonc.2022.07.1940

Key clinical point: Sacituzumab govitecan (SG) was more effective than chemotherapy in improving progression-free survival (PFS) and showed a manageable safety profile in patients with heavily pretreated, endocrine-resistant, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).

Major finding: SG vs chemotherapy significantly improved PFS (hazard ratio [HR] 0.66; P   =   .0003), with PFS rates being 46% vs 30% at 6 months and 21% vs 7% at 12 months, respectively. The most common grade ≥3 treatment-related adverse events with SG vs chemotherapy were neutropenia (51% vs 38%) and diarrhea (9% vs 1%).

Study details: Findings are the primary results of the phase 3 TROPiCS-02 trial including 543 patients with HR+/HER2− locally recurrent inoperable/metastatic BC who had received prior cyclin-dependent kinase 4/6 inhibitor with 2-4 lines of chemotherapy and were randomly assigned to receive SG or chemotherapy.

Disclosures: This study was supported by Gilead Sciences Inc. Four authors declared being employees of or stockowners in Gilead Sciences. The other authors reported ties with several sources, including Gilead.

Source: Rugo HS et al. Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2022 (Aug 26). Doi: 10.1200/JCO.22.01002

Key clinical point: Sacituzumab govitecan (SG) was more effective than chemotherapy in improving progression-free survival (PFS) and showed a manageable safety profile in patients with heavily pretreated, endocrine-resistant, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).

Major finding: SG vs chemotherapy significantly improved PFS (hazard ratio [HR] 0.66; P   =   .0003), with PFS rates being 46% vs 30% at 6 months and 21% vs 7% at 12 months, respectively. The most common grade ≥3 treatment-related adverse events with SG vs chemotherapy were neutropenia (51% vs 38%) and diarrhea (9% vs 1%).

Study details: Findings are the primary results of the phase 3 TROPiCS-02 trial including 543 patients with HR+/HER2− locally recurrent inoperable/metastatic BC who had received prior cyclin-dependent kinase 4/6 inhibitor with 2-4 lines of chemotherapy and were randomly assigned to receive SG or chemotherapy.

Disclosures: This study was supported by Gilead Sciences Inc. Four authors declared being employees of or stockowners in Gilead Sciences. The other authors reported ties with several sources, including Gilead.

Source: Rugo HS et al. Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2022 (Aug 26). Doi: 10.1200/JCO.22.01002

Key clinical point: Sacituzumab govitecan (SG) was more effective than chemotherapy in improving progression-free survival (PFS) and showed a manageable safety profile in patients with heavily pretreated, endocrine-resistant, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).

Major finding: SG vs chemotherapy significantly improved PFS (hazard ratio [HR] 0.66; P   =   .0003), with PFS rates being 46% vs 30% at 6 months and 21% vs 7% at 12 months, respectively. The most common grade ≥3 treatment-related adverse events with SG vs chemotherapy were neutropenia (51% vs 38%) and diarrhea (9% vs 1%).

Study details: Findings are the primary results of the phase 3 TROPiCS-02 trial including 543 patients with HR+/HER2− locally recurrent inoperable/metastatic BC who had received prior cyclin-dependent kinase 4/6 inhibitor with 2-4 lines of chemotherapy and were randomly assigned to receive SG or chemotherapy.

Disclosures: This study was supported by Gilead Sciences Inc. Four authors declared being employees of or stockowners in Gilead Sciences. The other authors reported ties with several sources, including Gilead.

Source: Rugo HS et al. Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2022 (Aug 26). Doi: 10.1200/JCO.22.01002

Key clinical point: De-escalation of locoregional radiotherapy, according to a predefined consensus-based study guideline, was oncologically safe in women with cT1-2N1 breast cancer (BC) who received primary chemotherapy.

Major finding: The 5-year locoregional recurrence rate was 2.2% (95% CI 1.4%-3.4%) in the overall cohort, with the rates being similar in the low- vs intermediate-risk group (P   =   .89), low- vs high-risk group (P   =   .75), and intermediate- vs high-risk group (P   =   .83) and the 5-year locoregional recurrence rate remaining < 4% as per the study guideline.

Study details: Findings are from a prospective registry study including 838 patients with cT1-2N1 invasive BC who were treated with ≥3 cycles of primary chemotherapy and surgery of the breast and axillary and were categorized into three predefined risk categorized based on axillary lymph node status.

Disclosures: This study was funded by the Dutch Cancer Society. Some authors declared holding patents, serving as the chair of a committee, or receiving grants, consulting fees, or financial and nonfinancial support from several sources.

Source: de Wild SR et al. De-escalation of radiotherapy after primary chemotherapy in cT1-2N1 breast cancer (RAPCHEM; BOOG 2010-03): 5-year follow-up results of a Dutch, prospective, registry study. Lancet Oncol. 2022;23(9):1201-1210 (Aug 8). Doi: 10.1016/S1470-2045(22)00482-X

Key clinical point: De-escalation of locoregional radiotherapy, according to a predefined consensus-based study guideline, was oncologically safe in women with cT1-2N1 breast cancer (BC) who received primary chemotherapy.

Major finding: The 5-year locoregional recurrence rate was 2.2% (95% CI 1.4%-3.4%) in the overall cohort, with the rates being similar in the low- vs intermediate-risk group (P   =   .89), low- vs high-risk group (P   =   .75), and intermediate- vs high-risk group (P   =   .83) and the 5-year locoregional recurrence rate remaining < 4% as per the study guideline.

Study details: Findings are from a prospective registry study including 838 patients with cT1-2N1 invasive BC who were treated with ≥3 cycles of primary chemotherapy and surgery of the breast and axillary and were categorized into three predefined risk categorized based on axillary lymph node status.

Disclosures: This study was funded by the Dutch Cancer Society. Some authors declared holding patents, serving as the chair of a committee, or receiving grants, consulting fees, or financial and nonfinancial support from several sources.

Source: de Wild SR et al. De-escalation of radiotherapy after primary chemotherapy in cT1-2N1 breast cancer (RAPCHEM; BOOG 2010-03): 5-year follow-up results of a Dutch, prospective, registry study. Lancet Oncol. 2022;23(9):1201-1210 (Aug 8). Doi: 10.1016/S1470-2045(22)00482-X

Key clinical point: De-escalation of locoregional radiotherapy, according to a predefined consensus-based study guideline, was oncologically safe in women with cT1-2N1 breast cancer (BC) who received primary chemotherapy.

Major finding: The 5-year locoregional recurrence rate was 2.2% (95% CI 1.4%-3.4%) in the overall cohort, with the rates being similar in the low- vs intermediate-risk group (P   =   .89), low- vs high-risk group (P   =   .75), and intermediate- vs high-risk group (P   =   .83) and the 5-year locoregional recurrence rate remaining < 4% as per the study guideline.

Study details: Findings are from a prospective registry study including 838 patients with cT1-2N1 invasive BC who were treated with ≥3 cycles of primary chemotherapy and surgery of the breast and axillary and were categorized into three predefined risk categorized based on axillary lymph node status.

Disclosures: This study was funded by the Dutch Cancer Society. Some authors declared holding patents, serving as the chair of a committee, or receiving grants, consulting fees, or financial and nonfinancial support from several sources.

Source: de Wild SR et al. De-escalation of radiotherapy after primary chemotherapy in cT1-2N1 breast cancer (RAPCHEM; BOOG 2010-03): 5-year follow-up results of a Dutch, prospective, registry study. Lancet Oncol. 2022;23(9):1201-1210 (Aug 8). Doi: 10.1016/S1470-2045(22)00482-X

As reproductive specialists, part of our obligation is to improve a woman’s or couple’s ability to conceive in the most cost-effective manner, ideally through natural attempts at conception. While assisted reproductive technologies (ART) have provided impressive pregnancy rates across many diagnoses, including unexplained infertility, this advanced procedure comes with a significant financial cost to those without insurance and an emotional burden from the lack of a guaranteed outcome. Infertility procedures have minimal associated but potentially significant risks, most importantly multiple gestations. Contrary to popular belief, ovulation induction with intrauterine insemination (IUI) treatment has a greater risk of high-order multiple gestation when compared with IVF, given the inability of the former to control the number of embryos that may enter and implant in the endometrial cavity and the increased use of single embryo transfers with the latter. The specialist should evaluate the woman or couple for the basic issues of ovulation, tubal, and sperm function, as well as for lifestyle and environmental factors that can impede reproduction. As a result, “one size fits all” should not apply to patients, specifically those with infertility. This month’s column will present the detrimental effect of environmental and lifestyle factors on the goal of enhancing fertility through natural cycles of urine luteinizing-hormone timed intercourse.

Nutrition

Often overlooked in the infertility evaluation, an optimal diet improves fertility for both partners. Processed meat has been associated with reduced sperm quality. In ART, red meat has been associated with decreased embryo blastocyst formation. Lower trans fatty acids and higher omega-3s may improve fecundity. Considered one of the best overall diets, the Mediterranean diet consists of plant-based foods, such as whole grains, vegetables, legumes, fruits, nuts, seeds, herbs, and spices. Olive oil is the main source of added fat whereas fish, seafood, dairy, and poultry should be eaten in moderation. Fatty fish, such as mackerel, herring, sardines, albacore tuna, and salmon, are rich in omega-3 fatty acids, which have been shown to improve fecundity and IVF success, and have a positive association with blastocyst embryo development.^1-3

Stress

The emotional effect of an infertility diagnosis has been demonstrated to be equivalent to a diagnosis of cancer and other major medical morbidities.⁴ Whether stress causes or is a result of infertility has been a longstanding debate.⁵ Nevertheless, stress is the number-one reason patients discontinue fertility treatment.⁶ As fertility specialists, we must be cognizant of the devastation endured by infertility patients and maintain an open dialogue, as well as provide resources for coping strategies and counseling.

One popular method of improving mental health and fertility has been acupuncture. Initial enthusiasm originated from one of the first studies to explore the use of acupuncture during IVF. This was a prospective randomized study that showed treated patients had an approximately 100% improvement in clinical pregnancy rate. Unfortunately, there was no appropriate control group, just untreated controls.⁷ A subsequent study by the same investigator added a placebo acupuncture control group and did not show a statistically significant increase in pregnancy rates.⁸ Finally, a meta-analysis and reanalysis did not demonstrate any improvement in pregnancy outcome, whereas three of the studies analyzed suggested a possible reduction in pregnancies; placebo acupuncture was shown to have a higher success rate.^9-11 While acupuncture is relatively safe, there appears to be only a placebo effect that may be helpful.

The effect of stress on reproduction has been addressed in one of my previous columns.
 

Alcohol and caffeine

The damaging effects of alcohol on the fetus during pregnancy are legion – abnormal facial features, microcephaly, low birth weight, hyperactive behavior, vision or hearing deficits, speech and language delays, and intellectual disability. Less known is the amount of alcohol that may have an effect during preconception. One of the first reports on the effect of alcohol on IVF concluded: a 13% decrease in the number of eggs aspirated; a 2.86 times increase in risk of not achieving pregnancy; and a 2.21 times increase in risk of miscarriage. For men, one additional drink per day increased the risk of not achieving a live birth from 2.28 to 8.32 times.¹² Subsequent studies demonstrate a 16% reduction in IVF pregnancies in women who have at least four drinks per week; when the couple drank at least four drinks per week, the pregnancy rate decreased by 21%.¹³

However, a study from Denmark did not demonstrate a negative effect of low to moderate pretreatment amounts of alcohol and caffeine on IVF outcomes.¹⁴ Nevertheless, there is evidence that reducing or abstaining from alcohol intake may improve IVF outcomes.¹⁵ While there have been reports of higher miscarriage rates from caffeine,^16,17 not all reports support a negative association.¹⁸

Smoking

The use of tobacco has been estimated to contribute to 13% of female infertility in a dose-response manner, including secondhand smoke. During ART, smoking reduces ovarian response to gonadotropins and decreases IVF success by up to 50%. Discontinuing smoking for 6 months beforehand appears to restore normal outcomes.^19-20

The American Society for Reproductive Medicine Practice Committee on smoking provides the following invaluable information to share with patients on the harmful reproductive effects of smoking:²¹

• Early menopause by accelerating the loss of eggs.
• Higher rates of miscarriage and ectopic pregnancy.
• A decrease in sperm function.
• Possible genetic damage to eggs and sperm.
• Reduced sperm in son from maternal smoking.

Weight and exercise

Compared with normal-weight women, those with obesity are three times more likely to have ovulatory dysfunction;²² a lower chance for conception;²³ and infertility.²⁴ Obese women have higher rates of miscarriage and recurrent miscarriage, reduced success with ART, an increased number of canceled cycles, and poorer quality oocytes retrieved. During pregnancy, obese women have three to four times higher rates of gestational diabetes and preeclampsia,²⁵ as well as likelihood of having a fetus with macrosomia and birth defects, and a 1.3-2.1 times higher risk of stillbirth.²⁶

Regarding physical activity, the rate of pregnancies (39.0% vs. 16.0%, P = .002) and live births (24.4% vs. 7.4% (P = .004) were higher with regular exercise vs. being sedentary. Obese women who exercised regularly had a live birth rate over threefold higher compared with those who were not active.²⁷ Moderation should be employed given that women who exercise to exhaustion have 2.3 times the odds of fertility problems.²⁸ In men, obesity has been shown to increase estrogens and reduce spermatogenesis. Exercise has improved semen parameters and testosterone. Paternal physical and sedentary activities were not related to clinical pregnancy or live birth rates following infertility treatment.²⁹ As in women, men experience negative effects from high-intensity exercise, including bicycling, which can result in decreased semen parameters, follicle-stimulating hormone, LH, and testosterone levels.³⁰

In couples desiring a more natural approach to infertility, fertility specialists can address environmental and lifestyle factors that may improve reproduction. When natural attempts at conception are not applicable or successful, IUI and ART are appropriate treatment options after considering estimated success rates as well as the physical, emotional, and financial investment of patients.

Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
 

References

1. Wise LA et al. Am J Epidemiol. 2018;187:60-74.

2. Chui Y-H. Hum Reprod. 2018;33:156-65.

3. Ferreira Braga DPA et al. Reprod Biomed Online. 2015;31:30-8.

4. Domar AD et al. J Psychosom Obstet Gynaecol. 1993;14[suppl]:45-52.

5. Trolice MP. J Assist Reprod Genet. 2021 Apr;38[4]:873-5.

6. Gameiro S et al. Hum Reprod Update. 2012;18[6]:652-69.

7. Paulus WE et al. Fertil Steril. 2002;77:721-4.

8. Paulus WE et al. Hum Reprod. 2003;18:S18(abstr).

9. Wing SSE et al. Hum Reprod. 2009;24:341-8.

10. Hong Zheng C et al. Fertil Steril. 2012;97:599-611.

11. Meldrum DR et al. Fertil Steril. 2013;99:1821-4.

12. Klonoff-Cohen H et al. Fertil Steril. 2003;79:330-9.

13. Rossi BV et al. Obstet Gynecol. 2011;117:136-42.

14. Abadia L et al. Hum Reprod. 2017;32:1846-54.

15. Gormack AA et al. Hum Reprod. 2015;30:1617.

16. James JE. BMJ Evid Based Med. 2021;26:114-15.

17. Gaskins AJ et al. Eur J Nutr. 2018 Feb;57:107-17.

18. Machtinger R et al. Fertil Steril. 2017;108:1026-33.

19. Hughes EG et al. Fertil Steril. 1994;62:807.

20. de Ziegler D et al. Fertil Steril. 2013;100:927-8.

21. Practice Committee of the American Society for Reproductive Medicine. Fertil Steril. 2018;110:611-8.

22. Brewer CJ, Balen AH. Reproduction. 2010;140:347-64.

23. Wise LA et al. Hum Reprod. 2010;25:253-64.

24. Silvestris S et al. Reprod Biol Endocrinol. 2018;16[1]:22.

25. Alwash SM et al. Obes Res Clin Pract. 2021;15:425-30.

26. Aune D et al. JAMA. 2014;311:1536-46.

27. Palomba S et al. Reprod Biomed Online. 2014;29:72-9.

28. Gudmundsdottir SL et al. Hum Reprod. 2009;24[12]:3196-204.

29. Gaskins AJ et al. Hum Reprod. 2014;29:2575-82.

30. Wise LA et al. Fertil Steril. 2011;95:1025-30.

As reproductive specialists, part of our obligation is to improve a woman’s or couple’s ability to conceive in the most cost-effective manner, ideally through natural attempts at conception. While assisted reproductive technologies (ART) have provided impressive pregnancy rates across many diagnoses, including unexplained infertility, this advanced procedure comes with a significant financial cost to those without insurance and an emotional burden from the lack of a guaranteed outcome. Infertility procedures have minimal associated but potentially significant risks, most importantly multiple gestations. Contrary to popular belief, ovulation induction with intrauterine insemination (IUI) treatment has a greater risk of high-order multiple gestation when compared with IVF, given the inability of the former to control the number of embryos that may enter and implant in the endometrial cavity and the increased use of single embryo transfers with the latter. The specialist should evaluate the woman or couple for the basic issues of ovulation, tubal, and sperm function, as well as for lifestyle and environmental factors that can impede reproduction. As a result, “one size fits all” should not apply to patients, specifically those with infertility. This month’s column will present the detrimental effect of environmental and lifestyle factors on the goal of enhancing fertility through natural cycles of urine luteinizing-hormone timed intercourse.

Nutrition

Often overlooked in the infertility evaluation, an optimal diet improves fertility for both partners. Processed meat has been associated with reduced sperm quality. In ART, red meat has been associated with decreased embryo blastocyst formation. Lower trans fatty acids and higher omega-3s may improve fecundity. Considered one of the best overall diets, the Mediterranean diet consists of plant-based foods, such as whole grains, vegetables, legumes, fruits, nuts, seeds, herbs, and spices. Olive oil is the main source of added fat whereas fish, seafood, dairy, and poultry should be eaten in moderation. Fatty fish, such as mackerel, herring, sardines, albacore tuna, and salmon, are rich in omega-3 fatty acids, which have been shown to improve fecundity and IVF success, and have a positive association with blastocyst embryo development.^1-3

Stress

The emotional effect of an infertility diagnosis has been demonstrated to be equivalent to a diagnosis of cancer and other major medical morbidities.⁴ Whether stress causes or is a result of infertility has been a longstanding debate.⁵ Nevertheless, stress is the number-one reason patients discontinue fertility treatment.⁶ As fertility specialists, we must be cognizant of the devastation endured by infertility patients and maintain an open dialogue, as well as provide resources for coping strategies and counseling.

One popular method of improving mental health and fertility has been acupuncture. Initial enthusiasm originated from one of the first studies to explore the use of acupuncture during IVF. This was a prospective randomized study that showed treated patients had an approximately 100% improvement in clinical pregnancy rate. Unfortunately, there was no appropriate control group, just untreated controls.⁷ A subsequent study by the same investigator added a placebo acupuncture control group and did not show a statistically significant increase in pregnancy rates.⁸ Finally, a meta-analysis and reanalysis did not demonstrate any improvement in pregnancy outcome, whereas three of the studies analyzed suggested a possible reduction in pregnancies; placebo acupuncture was shown to have a higher success rate.^9-11 While acupuncture is relatively safe, there appears to be only a placebo effect that may be helpful.

The effect of stress on reproduction has been addressed in one of my previous columns.
 

Alcohol and caffeine

The damaging effects of alcohol on the fetus during pregnancy are legion – abnormal facial features, microcephaly, low birth weight, hyperactive behavior, vision or hearing deficits, speech and language delays, and intellectual disability. Less known is the amount of alcohol that may have an effect during preconception. One of the first reports on the effect of alcohol on IVF concluded: a 13% decrease in the number of eggs aspirated; a 2.86 times increase in risk of not achieving pregnancy; and a 2.21 times increase in risk of miscarriage. For men, one additional drink per day increased the risk of not achieving a live birth from 2.28 to 8.32 times.¹² Subsequent studies demonstrate a 16% reduction in IVF pregnancies in women who have at least four drinks per week; when the couple drank at least four drinks per week, the pregnancy rate decreased by 21%.¹³

However, a study from Denmark did not demonstrate a negative effect of low to moderate pretreatment amounts of alcohol and caffeine on IVF outcomes.¹⁴ Nevertheless, there is evidence that reducing or abstaining from alcohol intake may improve IVF outcomes.¹⁵ While there have been reports of higher miscarriage rates from caffeine,^16,17 not all reports support a negative association.¹⁸

Smoking

The use of tobacco has been estimated to contribute to 13% of female infertility in a dose-response manner, including secondhand smoke. During ART, smoking reduces ovarian response to gonadotropins and decreases IVF success by up to 50%. Discontinuing smoking for 6 months beforehand appears to restore normal outcomes.^19-20

The American Society for Reproductive Medicine Practice Committee on smoking provides the following invaluable information to share with patients on the harmful reproductive effects of smoking:²¹

• Early menopause by accelerating the loss of eggs.
• Higher rates of miscarriage and ectopic pregnancy.
• A decrease in sperm function.
• Possible genetic damage to eggs and sperm.
• Reduced sperm in son from maternal smoking.

Weight and exercise

Compared with normal-weight women, those with obesity are three times more likely to have ovulatory dysfunction;²² a lower chance for conception;²³ and infertility.²⁴ Obese women have higher rates of miscarriage and recurrent miscarriage, reduced success with ART, an increased number of canceled cycles, and poorer quality oocytes retrieved. During pregnancy, obese women have three to four times higher rates of gestational diabetes and preeclampsia,²⁵ as well as likelihood of having a fetus with macrosomia and birth defects, and a 1.3-2.1 times higher risk of stillbirth.²⁶

Regarding physical activity, the rate of pregnancies (39.0% vs. 16.0%, P = .002) and live births (24.4% vs. 7.4% (P = .004) were higher with regular exercise vs. being sedentary. Obese women who exercised regularly had a live birth rate over threefold higher compared with those who were not active.²⁷ Moderation should be employed given that women who exercise to exhaustion have 2.3 times the odds of fertility problems.²⁸ In men, obesity has been shown to increase estrogens and reduce spermatogenesis. Exercise has improved semen parameters and testosterone. Paternal physical and sedentary activities were not related to clinical pregnancy or live birth rates following infertility treatment.²⁹ As in women, men experience negative effects from high-intensity exercise, including bicycling, which can result in decreased semen parameters, follicle-stimulating hormone, LH, and testosterone levels.³⁰

In couples desiring a more natural approach to infertility, fertility specialists can address environmental and lifestyle factors that may improve reproduction. When natural attempts at conception are not applicable or successful, IUI and ART are appropriate treatment options after considering estimated success rates as well as the physical, emotional, and financial investment of patients.

Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
 

References

1. Wise LA et al. Am J Epidemiol. 2018;187:60-74.

2. Chui Y-H. Hum Reprod. 2018;33:156-65.

3. Ferreira Braga DPA et al. Reprod Biomed Online. 2015;31:30-8.

4. Domar AD et al. J Psychosom Obstet Gynaecol. 1993;14[suppl]:45-52.

5. Trolice MP. J Assist Reprod Genet. 2021 Apr;38[4]:873-5.

6. Gameiro S et al. Hum Reprod Update. 2012;18[6]:652-69.

7. Paulus WE et al. Fertil Steril. 2002;77:721-4.

8. Paulus WE et al. Hum Reprod. 2003;18:S18(abstr).

9. Wing SSE et al. Hum Reprod. 2009;24:341-8.

10. Hong Zheng C et al. Fertil Steril. 2012;97:599-611.

11. Meldrum DR et al. Fertil Steril. 2013;99:1821-4.

12. Klonoff-Cohen H et al. Fertil Steril. 2003;79:330-9.

13. Rossi BV et al. Obstet Gynecol. 2011;117:136-42.

14. Abadia L et al. Hum Reprod. 2017;32:1846-54.

15. Gormack AA et al. Hum Reprod. 2015;30:1617.

16. James JE. BMJ Evid Based Med. 2021;26:114-15.

17. Gaskins AJ et al. Eur J Nutr. 2018 Feb;57:107-17.

18. Machtinger R et al. Fertil Steril. 2017;108:1026-33.

19. Hughes EG et al. Fertil Steril. 1994;62:807.

20. de Ziegler D et al. Fertil Steril. 2013;100:927-8.

21. Practice Committee of the American Society for Reproductive Medicine. Fertil Steril. 2018;110:611-8.

22. Brewer CJ, Balen AH. Reproduction. 2010;140:347-64.

23. Wise LA et al. Hum Reprod. 2010;25:253-64.

24. Silvestris S et al. Reprod Biol Endocrinol. 2018;16[1]:22.

25. Alwash SM et al. Obes Res Clin Pract. 2021;15:425-30.

26. Aune D et al. JAMA. 2014;311:1536-46.

27. Palomba S et al. Reprod Biomed Online. 2014;29:72-9.

28. Gudmundsdottir SL et al. Hum Reprod. 2009;24[12]:3196-204.

29. Gaskins AJ et al. Hum Reprod. 2014;29:2575-82.

30. Wise LA et al. Fertil Steril. 2011;95:1025-30.

As reproductive specialists, part of our obligation is to improve a woman’s or couple’s ability to conceive in the most cost-effective manner, ideally through natural attempts at conception. While assisted reproductive technologies (ART) have provided impressive pregnancy rates across many diagnoses, including unexplained infertility, this advanced procedure comes with a significant financial cost to those without insurance and an emotional burden from the lack of a guaranteed outcome. Infertility procedures have minimal associated but potentially significant risks, most importantly multiple gestations. Contrary to popular belief, ovulation induction with intrauterine insemination (IUI) treatment has a greater risk of high-order multiple gestation when compared with IVF, given the inability of the former to control the number of embryos that may enter and implant in the endometrial cavity and the increased use of single embryo transfers with the latter. The specialist should evaluate the woman or couple for the basic issues of ovulation, tubal, and sperm function, as well as for lifestyle and environmental factors that can impede reproduction. As a result, “one size fits all” should not apply to patients, specifically those with infertility. This month’s column will present the detrimental effect of environmental and lifestyle factors on the goal of enhancing fertility through natural cycles of urine luteinizing-hormone timed intercourse.

Nutrition

Often overlooked in the infertility evaluation, an optimal diet improves fertility for both partners. Processed meat has been associated with reduced sperm quality. In ART, red meat has been associated with decreased embryo blastocyst formation. Lower trans fatty acids and higher omega-3s may improve fecundity. Considered one of the best overall diets, the Mediterranean diet consists of plant-based foods, such as whole grains, vegetables, legumes, fruits, nuts, seeds, herbs, and spices. Olive oil is the main source of added fat whereas fish, seafood, dairy, and poultry should be eaten in moderation. Fatty fish, such as mackerel, herring, sardines, albacore tuna, and salmon, are rich in omega-3 fatty acids, which have been shown to improve fecundity and IVF success, and have a positive association with blastocyst embryo development.^1-3

Stress

The emotional effect of an infertility diagnosis has been demonstrated to be equivalent to a diagnosis of cancer and other major medical morbidities.⁴ Whether stress causes or is a result of infertility has been a longstanding debate.⁵ Nevertheless, stress is the number-one reason patients discontinue fertility treatment.⁶ As fertility specialists, we must be cognizant of the devastation endured by infertility patients and maintain an open dialogue, as well as provide resources for coping strategies and counseling.

One popular method of improving mental health and fertility has been acupuncture. Initial enthusiasm originated from one of the first studies to explore the use of acupuncture during IVF. This was a prospective randomized study that showed treated patients had an approximately 100% improvement in clinical pregnancy rate. Unfortunately, there was no appropriate control group, just untreated controls.⁷ A subsequent study by the same investigator added a placebo acupuncture control group and did not show a statistically significant increase in pregnancy rates.⁸ Finally, a meta-analysis and reanalysis did not demonstrate any improvement in pregnancy outcome, whereas three of the studies analyzed suggested a possible reduction in pregnancies; placebo acupuncture was shown to have a higher success rate.^9-11 While acupuncture is relatively safe, there appears to be only a placebo effect that may be helpful.

The effect of stress on reproduction has been addressed in one of my previous columns.
 

Alcohol and caffeine

The damaging effects of alcohol on the fetus during pregnancy are legion – abnormal facial features, microcephaly, low birth weight, hyperactive behavior, vision or hearing deficits, speech and language delays, and intellectual disability. Less known is the amount of alcohol that may have an effect during preconception. One of the first reports on the effect of alcohol on IVF concluded: a 13% decrease in the number of eggs aspirated; a 2.86 times increase in risk of not achieving pregnancy; and a 2.21 times increase in risk of miscarriage. For men, one additional drink per day increased the risk of not achieving a live birth from 2.28 to 8.32 times.¹² Subsequent studies demonstrate a 16% reduction in IVF pregnancies in women who have at least four drinks per week; when the couple drank at least four drinks per week, the pregnancy rate decreased by 21%.¹³

However, a study from Denmark did not demonstrate a negative effect of low to moderate pretreatment amounts of alcohol and caffeine on IVF outcomes.¹⁴ Nevertheless, there is evidence that reducing or abstaining from alcohol intake may improve IVF outcomes.¹⁵ While there have been reports of higher miscarriage rates from caffeine,^16,17 not all reports support a negative association.¹⁸

Smoking

The use of tobacco has been estimated to contribute to 13% of female infertility in a dose-response manner, including secondhand smoke. During ART, smoking reduces ovarian response to gonadotropins and decreases IVF success by up to 50%. Discontinuing smoking for 6 months beforehand appears to restore normal outcomes.^19-20

The American Society for Reproductive Medicine Practice Committee on smoking provides the following invaluable information to share with patients on the harmful reproductive effects of smoking:²¹

• Early menopause by accelerating the loss of eggs.
• Higher rates of miscarriage and ectopic pregnancy.
• A decrease in sperm function.
• Possible genetic damage to eggs and sperm.
• Reduced sperm in son from maternal smoking.

Weight and exercise

Compared with normal-weight women, those with obesity are three times more likely to have ovulatory dysfunction;²² a lower chance for conception;²³ and infertility.²⁴ Obese women have higher rates of miscarriage and recurrent miscarriage, reduced success with ART, an increased number of canceled cycles, and poorer quality oocytes retrieved. During pregnancy, obese women have three to four times higher rates of gestational diabetes and preeclampsia,²⁵ as well as likelihood of having a fetus with macrosomia and birth defects, and a 1.3-2.1 times higher risk of stillbirth.²⁶

Regarding physical activity, the rate of pregnancies (39.0% vs. 16.0%, P = .002) and live births (24.4% vs. 7.4% (P = .004) were higher with regular exercise vs. being sedentary. Obese women who exercised regularly had a live birth rate over threefold higher compared with those who were not active.²⁷ Moderation should be employed given that women who exercise to exhaustion have 2.3 times the odds of fertility problems.²⁸ In men, obesity has been shown to increase estrogens and reduce spermatogenesis. Exercise has improved semen parameters and testosterone. Paternal physical and sedentary activities were not related to clinical pregnancy or live birth rates following infertility treatment.²⁹ As in women, men experience negative effects from high-intensity exercise, including bicycling, which can result in decreased semen parameters, follicle-stimulating hormone, LH, and testosterone levels.³⁰

In couples desiring a more natural approach to infertility, fertility specialists can address environmental and lifestyle factors that may improve reproduction. When natural attempts at conception are not applicable or successful, IUI and ART are appropriate treatment options after considering estimated success rates as well as the physical, emotional, and financial investment of patients.

Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
 

References

1. Wise LA et al. Am J Epidemiol. 2018;187:60-74.

2. Chui Y-H. Hum Reprod. 2018;33:156-65.

3. Ferreira Braga DPA et al. Reprod Biomed Online. 2015;31:30-8.

4. Domar AD et al. J Psychosom Obstet Gynaecol. 1993;14[suppl]:45-52.

5. Trolice MP. J Assist Reprod Genet. 2021 Apr;38[4]:873-5.

6. Gameiro S et al. Hum Reprod Update. 2012;18[6]:652-69.

7. Paulus WE et al. Fertil Steril. 2002;77:721-4.

8. Paulus WE et al. Hum Reprod. 2003;18:S18(abstr).

9. Wing SSE et al. Hum Reprod. 2009;24:341-8.

10. Hong Zheng C et al. Fertil Steril. 2012;97:599-611.

11. Meldrum DR et al. Fertil Steril. 2013;99:1821-4.

12. Klonoff-Cohen H et al. Fertil Steril. 2003;79:330-9.

13. Rossi BV et al. Obstet Gynecol. 2011;117:136-42.

14. Abadia L et al. Hum Reprod. 2017;32:1846-54.

15. Gormack AA et al. Hum Reprod. 2015;30:1617.

16. James JE. BMJ Evid Based Med. 2021;26:114-15.

17. Gaskins AJ et al. Eur J Nutr. 2018 Feb;57:107-17.

18. Machtinger R et al. Fertil Steril. 2017;108:1026-33.

19. Hughes EG et al. Fertil Steril. 1994;62:807.

20. de Ziegler D et al. Fertil Steril. 2013;100:927-8.

21. Practice Committee of the American Society for Reproductive Medicine. Fertil Steril. 2018;110:611-8.

22. Brewer CJ, Balen AH. Reproduction. 2010;140:347-64.

23. Wise LA et al. Hum Reprod. 2010;25:253-64.

24. Silvestris S et al. Reprod Biol Endocrinol. 2018;16[1]:22.

25. Alwash SM et al. Obes Res Clin Pract. 2021;15:425-30.

26. Aune D et al. JAMA. 2014;311:1536-46.

27. Palomba S et al. Reprod Biomed Online. 2014;29:72-9.

28. Gudmundsdottir SL et al. Hum Reprod. 2009;24[12]:3196-204.

29. Gaskins AJ et al. Hum Reprod. 2014;29:2575-82.

30. Wise LA et al. Fertil Steril. 2011;95:1025-30.

Maya Iyer, MD, MEd, experienced bullying as a faculty member, and she sensed that she wasn’t alone. “The best ideas for research often come from individual experiences, in both personal and the professional academic medicine setting,” she said in an interview.

“And I was correct. I was not the only one who experienced bullying. In fact, the most severe bullying experiences among ... women physician leaders occurred when they were in leadership positions,” said Dr. Iyer, a pediatric emergency medicine physician at Nationwide Children’s Hospital in Columbus, Ohio.

She is a coauthor of a study that was published in JAMA Network Open in which investigators surveyed the existence of antibullying policies for faculty at almost 100 U.S. medical schools.

The researchers defined bullying as “a severe form of mistreatment [that] occurs in the medical setting when a power differential allows offenders to consciously target individuals through persistent negative actions to impede the education or career of the target.”

The study included 91 medical schools, of which 4 schools had antibullying policies that included the reporting of procedures. Of the 87 medical schools without antibullying policies, 60 had antiharrassment policies; of those schools, 10 of the schools’ websites cited bullying and antiharassment policies. Five schools required a login to access policies, and one school’s website had a broken webpage link, per the study.

“We need to bring the silent scourge of bullying to the forefront because bullying is causing a brain drain on the medical profession,” said Dr. Iyer. “Bullying has numerous downstream negative effects, including depression, anxiety, burnout stress, decreased patient care satisfaction, increased medical errors, and job attrition.”

She added: “Through bullying, we are losing voices in medicine just at that point in time where we are trying to diversify the workforce to improve representation of all physicians.”

Dr. Iyer’s team sampled the top 25 schools for research and the top 25 schools for primary care. They also took a random sampling from 25 schools for research and a random sampling from top 25 schools for primary care. They assessed antibullying policies, antiharassment policies that mentioned bullying, antiharrassment policies that did not mention bullying, and the absence of policies addressing these issues.

Policy comprehensiveness was another focus for the researchers. They evaluated whether the relevant policies included faculty members and articulated the institution’s commitment to providing a safe and healthy workplace. Other factors included defining bullying and the roles and responsibilities of employees and procedures for reporting bullying.
 

Physicians can’t be bystanders to bullying

Dr. Iyer called on physicians to “acknowledge that bullying in academic medicine exists and [to] speak up when they witness such events. This means transitioning from being a bystander to an upstander.”

She doesn’t let medical schools off the hook, however. Instead, she advocated having institutions “provide safe spaces and opportunities for near-peer mentoring so that targets of bullying can share stories.”

Regarding who is responsible for addressing bullying, Dr. Iyer is emphatic. “I do want to be clear that the onus of disrupting does not fall on the targets. Rather, we need to fix the systems in which such behavior is tolerated.”

Her advice to leaders in academic medicine is to create comprehensive, zero-retaliation bullying policies that include detailed reporting procedures. Dr. Iyer advised leaders to partner with colleagues in human resources, offices of equity, and ombudspersons to develop, implement, and enforce these policies.

The study authors reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Maya Iyer, MD, MEd, experienced bullying as a faculty member, and she sensed that she wasn’t alone. “The best ideas for research often come from individual experiences, in both personal and the professional academic medicine setting,” she said in an interview.

“And I was correct. I was not the only one who experienced bullying. In fact, the most severe bullying experiences among ... women physician leaders occurred when they were in leadership positions,” said Dr. Iyer, a pediatric emergency medicine physician at Nationwide Children’s Hospital in Columbus, Ohio.

She is a coauthor of a study that was published in JAMA Network Open in which investigators surveyed the existence of antibullying policies for faculty at almost 100 U.S. medical schools.

The researchers defined bullying as “a severe form of mistreatment [that] occurs in the medical setting when a power differential allows offenders to consciously target individuals through persistent negative actions to impede the education or career of the target.”

The study included 91 medical schools, of which 4 schools had antibullying policies that included the reporting of procedures. Of the 87 medical schools without antibullying policies, 60 had antiharrassment policies; of those schools, 10 of the schools’ websites cited bullying and antiharassment policies. Five schools required a login to access policies, and one school’s website had a broken webpage link, per the study.

“We need to bring the silent scourge of bullying to the forefront because bullying is causing a brain drain on the medical profession,” said Dr. Iyer. “Bullying has numerous downstream negative effects, including depression, anxiety, burnout stress, decreased patient care satisfaction, increased medical errors, and job attrition.”

She added: “Through bullying, we are losing voices in medicine just at that point in time where we are trying to diversify the workforce to improve representation of all physicians.”

Dr. Iyer’s team sampled the top 25 schools for research and the top 25 schools for primary care. They also took a random sampling from 25 schools for research and a random sampling from top 25 schools for primary care. They assessed antibullying policies, antiharassment policies that mentioned bullying, antiharrassment policies that did not mention bullying, and the absence of policies addressing these issues.

Policy comprehensiveness was another focus for the researchers. They evaluated whether the relevant policies included faculty members and articulated the institution’s commitment to providing a safe and healthy workplace. Other factors included defining bullying and the roles and responsibilities of employees and procedures for reporting bullying.
 

Physicians can’t be bystanders to bullying

Dr. Iyer called on physicians to “acknowledge that bullying in academic medicine exists and [to] speak up when they witness such events. This means transitioning from being a bystander to an upstander.”

She doesn’t let medical schools off the hook, however. Instead, she advocated having institutions “provide safe spaces and opportunities for near-peer mentoring so that targets of bullying can share stories.”

Regarding who is responsible for addressing bullying, Dr. Iyer is emphatic. “I do want to be clear that the onus of disrupting does not fall on the targets. Rather, we need to fix the systems in which such behavior is tolerated.”

Her advice to leaders in academic medicine is to create comprehensive, zero-retaliation bullying policies that include detailed reporting procedures. Dr. Iyer advised leaders to partner with colleagues in human resources, offices of equity, and ombudspersons to develop, implement, and enforce these policies.

The study authors reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Maya Iyer, MD, MEd, experienced bullying as a faculty member, and she sensed that she wasn’t alone. “The best ideas for research often come from individual experiences, in both personal and the professional academic medicine setting,” she said in an interview.

“And I was correct. I was not the only one who experienced bullying. In fact, the most severe bullying experiences among ... women physician leaders occurred when they were in leadership positions,” said Dr. Iyer, a pediatric emergency medicine physician at Nationwide Children’s Hospital in Columbus, Ohio.

She is a coauthor of a study that was published in JAMA Network Open in which investigators surveyed the existence of antibullying policies for faculty at almost 100 U.S. medical schools.

The researchers defined bullying as “a severe form of mistreatment [that] occurs in the medical setting when a power differential allows offenders to consciously target individuals through persistent negative actions to impede the education or career of the target.”

The study included 91 medical schools, of which 4 schools had antibullying policies that included the reporting of procedures. Of the 87 medical schools without antibullying policies, 60 had antiharrassment policies; of those schools, 10 of the schools’ websites cited bullying and antiharassment policies. Five schools required a login to access policies, and one school’s website had a broken webpage link, per the study.

“We need to bring the silent scourge of bullying to the forefront because bullying is causing a brain drain on the medical profession,” said Dr. Iyer. “Bullying has numerous downstream negative effects, including depression, anxiety, burnout stress, decreased patient care satisfaction, increased medical errors, and job attrition.”

She added: “Through bullying, we are losing voices in medicine just at that point in time where we are trying to diversify the workforce to improve representation of all physicians.”

Dr. Iyer’s team sampled the top 25 schools for research and the top 25 schools for primary care. They also took a random sampling from 25 schools for research and a random sampling from top 25 schools for primary care. They assessed antibullying policies, antiharassment policies that mentioned bullying, antiharrassment policies that did not mention bullying, and the absence of policies addressing these issues.

Policy comprehensiveness was another focus for the researchers. They evaluated whether the relevant policies included faculty members and articulated the institution’s commitment to providing a safe and healthy workplace. Other factors included defining bullying and the roles and responsibilities of employees and procedures for reporting bullying.
 

Physicians can’t be bystanders to bullying

Dr. Iyer called on physicians to “acknowledge that bullying in academic medicine exists and [to] speak up when they witness such events. This means transitioning from being a bystander to an upstander.”

She doesn’t let medical schools off the hook, however. Instead, she advocated having institutions “provide safe spaces and opportunities for near-peer mentoring so that targets of bullying can share stories.”

Regarding who is responsible for addressing bullying, Dr. Iyer is emphatic. “I do want to be clear that the onus of disrupting does not fall on the targets. Rather, we need to fix the systems in which such behavior is tolerated.”

Her advice to leaders in academic medicine is to create comprehensive, zero-retaliation bullying policies that include detailed reporting procedures. Dr. Iyer advised leaders to partner with colleagues in human resources, offices of equity, and ombudspersons to develop, implement, and enforce these policies.

The study authors reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

The diagnosis for this case is psoriatic arthritis (PsA). The 2018 American College of Rheumatology/National Psoriasis Foundation guidelines offer current treatment recommendations for this condition. For patients with active PsA who are treatment-naive, treatment recommendations are:

• Tumor necrosis factor (TNF) inhibitors are preferred over oral small molecules (OSMs), interleukin (IL)–17 inhibitors, or IL-12/23 inhibitors
• OSMs are recommended over IL-17 inhibitors or IL-12/23 inhibitors
• Methotrexate is recommended over nonsteroidal anti-inflammatory drugs
• IL-17 inhibitors are recommended over IL-12/23 inhibitors

Treatment recommendations for patients with active PsA despite the use of OSMs are: 

• Switching to a TNF inhibitor over another OSM, IL-17 or IL-12/23 inhibitors, abatacept, or tofacitinib
• Switching to an IL-17 inhibitor over another OSM, IL-12/23 inhibitor, abatacept, or tofacitinib
• Switching to an IL-12/23 inhibitor over another OSM, abatacept, or tofacitinib.

International groups, such as the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European League Against Rheumatism (EULAR), have published treatment recommendations as well. These address both PsA and, to a lesser extent, psoriasis. The GRAPPA recommendations consider six domains of involvement (peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, and nail psoriasis) and use a grid approach to account for various levels of disease activity and severity. The EULAR recommendations use an algorithmic approach that focuses mainly on musculoskeletal manifestations, specifically peripheral arthritis; manifestations, such as dactylitis, enthesitis, and skin and nail involvement, are considered separately.

Psoriasis precedes the onset of PsA in 60%-80% of patients (sometimes by up to 20 years but usually by less than 10 years); but in as many as 15%-20% of patients, arthritis appears before psoriasis. On occasion, arthritis and psoriasis appear simultaneously.

Patients with PsA are typically seronegative for rheumatoid factor and antinuclear antibody; antinuclear antibody titers in persons with PsA do not differ from those of age- and sex-matched controls. C-reactive protein may be elevated but is often normal. Lack of C-reactive protein elevation, however, does not mean that systemic inflammation is absent but rather indicates that a different type of systemic inflammation may be at play for those patients.

Herbert S. Diamond, MD, Professor of Medicine (retired), Temple University School of Medicine, University of Pittsburgh; Chairman, Department of Medicine Emeritus, Western Pennsylvania Hospital, Pittsburgh, PA.

Herbert S. Diamond, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The diagnosis for this case is psoriatic arthritis (PsA). The 2018 American College of Rheumatology/National Psoriasis Foundation guidelines offer current treatment recommendations for this condition. For patients with active PsA who are treatment-naive, treatment recommendations are:

• Tumor necrosis factor (TNF) inhibitors are preferred over oral small molecules (OSMs), interleukin (IL)–17 inhibitors, or IL-12/23 inhibitors
• OSMs are recommended over IL-17 inhibitors or IL-12/23 inhibitors
• Methotrexate is recommended over nonsteroidal anti-inflammatory drugs
• IL-17 inhibitors are recommended over IL-12/23 inhibitors

Treatment recommendations for patients with active PsA despite the use of OSMs are: 

• Switching to a TNF inhibitor over another OSM, IL-17 or IL-12/23 inhibitors, abatacept, or tofacitinib
• Switching to an IL-17 inhibitor over another OSM, IL-12/23 inhibitor, abatacept, or tofacitinib
• Switching to an IL-12/23 inhibitor over another OSM, abatacept, or tofacitinib.

International groups, such as the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European League Against Rheumatism (EULAR), have published treatment recommendations as well. These address both PsA and, to a lesser extent, psoriasis. The GRAPPA recommendations consider six domains of involvement (peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, and nail psoriasis) and use a grid approach to account for various levels of disease activity and severity. The EULAR recommendations use an algorithmic approach that focuses mainly on musculoskeletal manifestations, specifically peripheral arthritis; manifestations, such as dactylitis, enthesitis, and skin and nail involvement, are considered separately.

Psoriasis precedes the onset of PsA in 60%-80% of patients (sometimes by up to 20 years but usually by less than 10 years); but in as many as 15%-20% of patients, arthritis appears before psoriasis. On occasion, arthritis and psoriasis appear simultaneously.

Patients with PsA are typically seronegative for rheumatoid factor and antinuclear antibody; antinuclear antibody titers in persons with PsA do not differ from those of age- and sex-matched controls. C-reactive protein may be elevated but is often normal. Lack of C-reactive protein elevation, however, does not mean that systemic inflammation is absent but rather indicates that a different type of systemic inflammation may be at play for those patients.

Herbert S. Diamond, MD, Professor of Medicine (retired), Temple University School of Medicine, University of Pittsburgh; Chairman, Department of Medicine Emeritus, Western Pennsylvania Hospital, Pittsburgh, PA.

Herbert S. Diamond, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The diagnosis for this case is psoriatic arthritis (PsA). The 2018 American College of Rheumatology/National Psoriasis Foundation guidelines offer current treatment recommendations for this condition. For patients with active PsA who are treatment-naive, treatment recommendations are:

• Tumor necrosis factor (TNF) inhibitors are preferred over oral small molecules (OSMs), interleukin (IL)–17 inhibitors, or IL-12/23 inhibitors
• OSMs are recommended over IL-17 inhibitors or IL-12/23 inhibitors
• Methotrexate is recommended over nonsteroidal anti-inflammatory drugs
• IL-17 inhibitors are recommended over IL-12/23 inhibitors

Treatment recommendations for patients with active PsA despite the use of OSMs are: 

• Switching to a TNF inhibitor over another OSM, IL-17 or IL-12/23 inhibitors, abatacept, or tofacitinib
• Switching to an IL-17 inhibitor over another OSM, IL-12/23 inhibitor, abatacept, or tofacitinib
• Switching to an IL-12/23 inhibitor over another OSM, abatacept, or tofacitinib.

International groups, such as the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European League Against Rheumatism (EULAR), have published treatment recommendations as well. These address both PsA and, to a lesser extent, psoriasis. The GRAPPA recommendations consider six domains of involvement (peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, and nail psoriasis) and use a grid approach to account for various levels of disease activity and severity. The EULAR recommendations use an algorithmic approach that focuses mainly on musculoskeletal manifestations, specifically peripheral arthritis; manifestations, such as dactylitis, enthesitis, and skin and nail involvement, are considered separately.

Psoriasis precedes the onset of PsA in 60%-80% of patients (sometimes by up to 20 years but usually by less than 10 years); but in as many as 15%-20% of patients, arthritis appears before psoriasis. On occasion, arthritis and psoriasis appear simultaneously.

Patients with PsA are typically seronegative for rheumatoid factor and antinuclear antibody; antinuclear antibody titers in persons with PsA do not differ from those of age- and sex-matched controls. C-reactive protein may be elevated but is often normal. Lack of C-reactive protein elevation, however, does not mean that systemic inflammation is absent but rather indicates that a different type of systemic inflammation may be at play for those patients.

Herbert S. Diamond, MD, Professor of Medicine (retired), Temple University School of Medicine, University of Pittsburgh; Chairman, Department of Medicine Emeritus, Western Pennsylvania Hospital, Pittsburgh, PA.

Herbert S. Diamond, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

GHENT, BELGIUM – Over 10% of patients referred by chiropractors to rheumatology had undiagnosed spondyloarthritis, with axial spondyloarthritis being the most common, according to new data. The U.S. study was aimed at understanding what proportion of back pain patients have undiagnosed spondyloarthritis.

The study also found that the most common cause for which patients see chiropractors is neck/cervical pain.

Atul Deodhar, MD, MRCP, rheumatologist and medical director of rheumatology clinics at Oregon Health & Science University, Portland, was senior author of the poster that was presented at the 13th International Congress of Spondyloarthritides.

“In the U.S., many people with back pain go to chiropractors, but many chiropractors are not aware of axial spondyloarthritis [axSpA] terminology, and very little – if anything – is published in chiropractic literature, “ he said in an interview.

He remarked that the study highlighted the need to develop a better strategy to identify undiagnosed patients, because the yield found in their study was poor (13%). “Patient-reported spondyloarthritis criteria are often poor, and do not match rheumatologist-inquired history,” he noted, adding that, “inflammatory back pain is in fact a poor ‘entry point.’ ”

Ulrich Weber, MD, rheumatologist from the Practice Buchsbaum in Schaffhausen, Switzerland, commented on the findings, saying he often receives delayed referrals from chiropractors, so “it would be very useful if patients could be more easily and accurately identifiable via this route, but the problem is chiropractors do not have a specific training to spot spondyloarthritis.”

He added that he welcomed the study but noted, “the criteria used to identify patients in this study are broad and I’d worry that it would inundate our rheumatology practice. There remains a real need for a good method of identifying the patients.”
 

Referral to rheumatology

Back pain is highly prevalent in the general population, with a global mean lifetime prevalence of 38.9%. Chiropractors treat many patients with back pain of unknown cause.

“In this study, we wanted to see what percentage of patients in chiropractic practice have undiagnosed axial spondyloarthritis, and what are the common complaints. Our hypothesis was that chiropractors may be missing such patients,” Dr. Deodhar explained.

Dr. Deodhar and colleagues recruited chiropractors from four different parts of the city of Portland into the study. “We think Portland, Oregon, is a typical U.S. city, and our results could be generalized. However, this is our impression alone,” he remarked.

Adults, under the age of 45 years who attended a participating chiropractic clinics between November 2020 and November 2021 for chronic back pain and without a prior diagnosis of spondyloarthritis were eligible for inclusion.

If the patient reported at least one feature of spondyloarthritis in the screening questionnaire they were referred to a rheumatologist for a diagnostic assessment. This assessment involved taking history by telephone, both laboratory tests and imaging, and the patients were categorized as radiographic axSpA, nonradiographic axSpA, peripheral SpA, or no SpA.

The screening questionnaire included the following examples: If the patient was under 45 years and had chronic pain in back, hip or buttocks, then they were asked for more information including whether their pain was gradual (insidious) in onset; if the pain started before the age of 40; and if the pain improved with physical activities or movements. Use of drugs was investigated including whether the pain improved significantly with NSAIDs and whether the patient has current or past heel pains, particularly when waking up in the morning. They were also asked if they have experienced skin psoriasis. Other questions were asked about the presence of uveitis, iritis, family history of psoriasis, inflammatory bowel disease, or ankylosing spondylitis, and whether the patient had unexplained joint pains plus joint swelling.
 

Ten percent of patients referred to rheumatology

A total of 3,103 visits to chiropractor clinics were included, of which 115 patients were referred to a rheumatologist. Eventually, 63 patients were fully assessed by a rheumatologist.

Of those patients who were fully assessed, 12.7% has spondyloarthritis, with one having confirmed radiographic axSpA, five having nonradiographic SpA, and two having peripheral spondyloarthritis or psoriatic arthritis.

Based on the referral questionnaire, all patients reported at least four SpA criteria were met, said Dr. Deodhar.

Of those patients diagnosed with SpA, 14% (1) has elevated C-reactive protein (CRP) level, 14% (1) were HLA-B27 positive, and 14% (1) were identified as having both elevated CRP and HLA-B27 positivity. Sacroiliac joint inflammation was found in 14% (1) on MRI and one had sacroiliac joint inflammation according to modified New York criteria. One (14%) had both sacroiliac joint inflammation on MRI and elevated CRP, and 14% (1) had both sacroiliac joint inflammation and was HLA-B27 positive.

The top complaints reported by patients at chiropractor clinics were neck and cervical spine pain/spasm (16.8%); followed by acute low back pain (11.7%); acute upper back (7.1%); and chronic lower back pain (6.9%).
 

No patients with more than 10 SpA criteria

The performance of an initial diagnostic assessment based on patient reported SpA criteria, as compared with the outcome of the full diagnosis (by a rheumatologist) showed that patients with one to four SpA criteria had a sensitivity of 0.50 (95% confidence interval, 0.15-0.85), and specificity of 0.73 (95% CI, 0.61-0.84). This increased to sensitivity of 0.60 (95% CI, 0.17-1.03), and specificity of 0.61 (95% CI, 0.44-0.77) when six SpA criteria were present.

Dr. Deodhar said the results supported a need to further develop the chiropractor’s role in identifying the right patients for referral, and that the study showed that a referral strategy is required to find undiagnosed patients with spondyloarthritis from chiropractic offices. “Chiropractors need education for axSpA, when to suspect, and when to refer,” he asserted. “What referral strategy to use is for debate – the ASAS [Assessment in SpondyloArthritis international Society] strategy is too sensitive and not specific enough.”

Dr. Deodhar noted that SPARTAN (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network) is working on a referral strategy that is likely to be more specific, and that more data would be forthcoming soon.

Dr. Deodhar declared affiliations with multiple companies involved in the field unrelated to the study. Dr. Weber declared no relevant disclosures.

GHENT, BELGIUM – Over 10% of patients referred by chiropractors to rheumatology had undiagnosed spondyloarthritis, with axial spondyloarthritis being the most common, according to new data. The U.S. study was aimed at understanding what proportion of back pain patients have undiagnosed spondyloarthritis.

The study also found that the most common cause for which patients see chiropractors is neck/cervical pain.

Atul Deodhar, MD, MRCP, rheumatologist and medical director of rheumatology clinics at Oregon Health & Science University, Portland, was senior author of the poster that was presented at the 13th International Congress of Spondyloarthritides.

“In the U.S., many people with back pain go to chiropractors, but many chiropractors are not aware of axial spondyloarthritis [axSpA] terminology, and very little – if anything – is published in chiropractic literature, “ he said in an interview.

He remarked that the study highlighted the need to develop a better strategy to identify undiagnosed patients, because the yield found in their study was poor (13%). “Patient-reported spondyloarthritis criteria are often poor, and do not match rheumatologist-inquired history,” he noted, adding that, “inflammatory back pain is in fact a poor ‘entry point.’ ”

Ulrich Weber, MD, rheumatologist from the Practice Buchsbaum in Schaffhausen, Switzerland, commented on the findings, saying he often receives delayed referrals from chiropractors, so “it would be very useful if patients could be more easily and accurately identifiable via this route, but the problem is chiropractors do not have a specific training to spot spondyloarthritis.”

He added that he welcomed the study but noted, “the criteria used to identify patients in this study are broad and I’d worry that it would inundate our rheumatology practice. There remains a real need for a good method of identifying the patients.”
 

Referral to rheumatology

Back pain is highly prevalent in the general population, with a global mean lifetime prevalence of 38.9%. Chiropractors treat many patients with back pain of unknown cause.

“In this study, we wanted to see what percentage of patients in chiropractic practice have undiagnosed axial spondyloarthritis, and what are the common complaints. Our hypothesis was that chiropractors may be missing such patients,” Dr. Deodhar explained.

Dr. Deodhar and colleagues recruited chiropractors from four different parts of the city of Portland into the study. “We think Portland, Oregon, is a typical U.S. city, and our results could be generalized. However, this is our impression alone,” he remarked.

Adults, under the age of 45 years who attended a participating chiropractic clinics between November 2020 and November 2021 for chronic back pain and without a prior diagnosis of spondyloarthritis were eligible for inclusion.

If the patient reported at least one feature of spondyloarthritis in the screening questionnaire they were referred to a rheumatologist for a diagnostic assessment. This assessment involved taking history by telephone, both laboratory tests and imaging, and the patients were categorized as radiographic axSpA, nonradiographic axSpA, peripheral SpA, or no SpA.

The screening questionnaire included the following examples: If the patient was under 45 years and had chronic pain in back, hip or buttocks, then they were asked for more information including whether their pain was gradual (insidious) in onset; if the pain started before the age of 40; and if the pain improved with physical activities or movements. Use of drugs was investigated including whether the pain improved significantly with NSAIDs and whether the patient has current or past heel pains, particularly when waking up in the morning. They were also asked if they have experienced skin psoriasis. Other questions were asked about the presence of uveitis, iritis, family history of psoriasis, inflammatory bowel disease, or ankylosing spondylitis, and whether the patient had unexplained joint pains plus joint swelling.
 

Ten percent of patients referred to rheumatology

A total of 3,103 visits to chiropractor clinics were included, of which 115 patients were referred to a rheumatologist. Eventually, 63 patients were fully assessed by a rheumatologist.

Of those patients who were fully assessed, 12.7% has spondyloarthritis, with one having confirmed radiographic axSpA, five having nonradiographic SpA, and two having peripheral spondyloarthritis or psoriatic arthritis.

Based on the referral questionnaire, all patients reported at least four SpA criteria were met, said Dr. Deodhar.

Of those patients diagnosed with SpA, 14% (1) has elevated C-reactive protein (CRP) level, 14% (1) were HLA-B27 positive, and 14% (1) were identified as having both elevated CRP and HLA-B27 positivity. Sacroiliac joint inflammation was found in 14% (1) on MRI and one had sacroiliac joint inflammation according to modified New York criteria. One (14%) had both sacroiliac joint inflammation on MRI and elevated CRP, and 14% (1) had both sacroiliac joint inflammation and was HLA-B27 positive.

The top complaints reported by patients at chiropractor clinics were neck and cervical spine pain/spasm (16.8%); followed by acute low back pain (11.7%); acute upper back (7.1%); and chronic lower back pain (6.9%).
 

No patients with more than 10 SpA criteria

The performance of an initial diagnostic assessment based on patient reported SpA criteria, as compared with the outcome of the full diagnosis (by a rheumatologist) showed that patients with one to four SpA criteria had a sensitivity of 0.50 (95% confidence interval, 0.15-0.85), and specificity of 0.73 (95% CI, 0.61-0.84). This increased to sensitivity of 0.60 (95% CI, 0.17-1.03), and specificity of 0.61 (95% CI, 0.44-0.77) when six SpA criteria were present.

Dr. Deodhar said the results supported a need to further develop the chiropractor’s role in identifying the right patients for referral, and that the study showed that a referral strategy is required to find undiagnosed patients with spondyloarthritis from chiropractic offices. “Chiropractors need education for axSpA, when to suspect, and when to refer,” he asserted. “What referral strategy to use is for debate – the ASAS [Assessment in SpondyloArthritis international Society] strategy is too sensitive and not specific enough.”

Dr. Deodhar noted that SPARTAN (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network) is working on a referral strategy that is likely to be more specific, and that more data would be forthcoming soon.

Dr. Deodhar declared affiliations with multiple companies involved in the field unrelated to the study. Dr. Weber declared no relevant disclosures.

GHENT, BELGIUM – Over 10% of patients referred by chiropractors to rheumatology had undiagnosed spondyloarthritis, with axial spondyloarthritis being the most common, according to new data. The U.S. study was aimed at understanding what proportion of back pain patients have undiagnosed spondyloarthritis.

The study also found that the most common cause for which patients see chiropractors is neck/cervical pain.

Atul Deodhar, MD, MRCP, rheumatologist and medical director of rheumatology clinics at Oregon Health & Science University, Portland, was senior author of the poster that was presented at the 13th International Congress of Spondyloarthritides.

“In the U.S., many people with back pain go to chiropractors, but many chiropractors are not aware of axial spondyloarthritis [axSpA] terminology, and very little – if anything – is published in chiropractic literature, “ he said in an interview.

He remarked that the study highlighted the need to develop a better strategy to identify undiagnosed patients, because the yield found in their study was poor (13%). “Patient-reported spondyloarthritis criteria are often poor, and do not match rheumatologist-inquired history,” he noted, adding that, “inflammatory back pain is in fact a poor ‘entry point.’ ”

Ulrich Weber, MD, rheumatologist from the Practice Buchsbaum in Schaffhausen, Switzerland, commented on the findings, saying he often receives delayed referrals from chiropractors, so “it would be very useful if patients could be more easily and accurately identifiable via this route, but the problem is chiropractors do not have a specific training to spot spondyloarthritis.”

He added that he welcomed the study but noted, “the criteria used to identify patients in this study are broad and I’d worry that it would inundate our rheumatology practice. There remains a real need for a good method of identifying the patients.”
 

Referral to rheumatology

Back pain is highly prevalent in the general population, with a global mean lifetime prevalence of 38.9%. Chiropractors treat many patients with back pain of unknown cause.

“In this study, we wanted to see what percentage of patients in chiropractic practice have undiagnosed axial spondyloarthritis, and what are the common complaints. Our hypothesis was that chiropractors may be missing such patients,” Dr. Deodhar explained.

Dr. Deodhar and colleagues recruited chiropractors from four different parts of the city of Portland into the study. “We think Portland, Oregon, is a typical U.S. city, and our results could be generalized. However, this is our impression alone,” he remarked.

Adults, under the age of 45 years who attended a participating chiropractic clinics between November 2020 and November 2021 for chronic back pain and without a prior diagnosis of spondyloarthritis were eligible for inclusion.

If the patient reported at least one feature of spondyloarthritis in the screening questionnaire they were referred to a rheumatologist for a diagnostic assessment. This assessment involved taking history by telephone, both laboratory tests and imaging, and the patients were categorized as radiographic axSpA, nonradiographic axSpA, peripheral SpA, or no SpA.

The screening questionnaire included the following examples: If the patient was under 45 years and had chronic pain in back, hip or buttocks, then they were asked for more information including whether their pain was gradual (insidious) in onset; if the pain started before the age of 40; and if the pain improved with physical activities or movements. Use of drugs was investigated including whether the pain improved significantly with NSAIDs and whether the patient has current or past heel pains, particularly when waking up in the morning. They were also asked if they have experienced skin psoriasis. Other questions were asked about the presence of uveitis, iritis, family history of psoriasis, inflammatory bowel disease, or ankylosing spondylitis, and whether the patient had unexplained joint pains plus joint swelling.
 

Ten percent of patients referred to rheumatology

A total of 3,103 visits to chiropractor clinics were included, of which 115 patients were referred to a rheumatologist. Eventually, 63 patients were fully assessed by a rheumatologist.

Of those patients who were fully assessed, 12.7% has spondyloarthritis, with one having confirmed radiographic axSpA, five having nonradiographic SpA, and two having peripheral spondyloarthritis or psoriatic arthritis.

Based on the referral questionnaire, all patients reported at least four SpA criteria were met, said Dr. Deodhar.

Of those patients diagnosed with SpA, 14% (1) has elevated C-reactive protein (CRP) level, 14% (1) were HLA-B27 positive, and 14% (1) were identified as having both elevated CRP and HLA-B27 positivity. Sacroiliac joint inflammation was found in 14% (1) on MRI and one had sacroiliac joint inflammation according to modified New York criteria. One (14%) had both sacroiliac joint inflammation on MRI and elevated CRP, and 14% (1) had both sacroiliac joint inflammation and was HLA-B27 positive.

The top complaints reported by patients at chiropractor clinics were neck and cervical spine pain/spasm (16.8%); followed by acute low back pain (11.7%); acute upper back (7.1%); and chronic lower back pain (6.9%).
 

No patients with more than 10 SpA criteria

The performance of an initial diagnostic assessment based on patient reported SpA criteria, as compared with the outcome of the full diagnosis (by a rheumatologist) showed that patients with one to four SpA criteria had a sensitivity of 0.50 (95% confidence interval, 0.15-0.85), and specificity of 0.73 (95% CI, 0.61-0.84). This increased to sensitivity of 0.60 (95% CI, 0.17-1.03), and specificity of 0.61 (95% CI, 0.44-0.77) when six SpA criteria were present.

Dr. Deodhar said the results supported a need to further develop the chiropractor’s role in identifying the right patients for referral, and that the study showed that a referral strategy is required to find undiagnosed patients with spondyloarthritis from chiropractic offices. “Chiropractors need education for axSpA, when to suspect, and when to refer,” he asserted. “What referral strategy to use is for debate – the ASAS [Assessment in SpondyloArthritis international Society] strategy is too sensitive and not specific enough.”

Dr. Deodhar noted that SPARTAN (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network) is working on a referral strategy that is likely to be more specific, and that more data would be forthcoming soon.

Dr. Deodhar declared affiliations with multiple companies involved in the field unrelated to the study. Dr. Weber declared no relevant disclosures.

Migraine affects more than 1 in 6 US adults. This figure masks the fact that migraine is a predominantly female disorder; compared with men, 3-month migraine prevalence is more than 2-fold higher (21% vs. 10%) in women. Research by the World Health Organization has established migraine as second among the world’s causes of disability, and first among women of reproductive age.  

Despite this burden of illness, migraine is often not diagnosed or treated effectively. General lifestyle advice such as maintaining a healthy weight, sleep hygiene, regular meals, regular exercise and hydration, and management of identified predisposing or triggering factors—together with optimization of symptomatic migraine treatment—can benefit all women with migraine. However, specific hormonal events such as menstruation, hormonal contraception, pregnancy, menopause, and hormone replacement therapy have variable, but often predictable, effects on the frequency and severity of migraine. At each of these life stages, there are specific opportunities to intervene and relieve migraine burden.

Menstrual migraine

Menstruation is one of the most significant risk factors for migraine, notably migraine without aura, with increased prevalence during a 5-day perimenstrual window that starts 2 days before the onset of menses and continues through the first 3 days of menstruation.

The International Headache Society (IHS) recognizes 2 types of menstrual migraine. There is menstrually related migraine, which is migraine without aura that regularly occurs on or between day −2 to +3 of menstruation (there is no day 0), with additional attacks of migraine with or without aura at other times of the cycle. There is also pure menstrual migraine, which is migraine without aura that occurs only on or between day −2 to +3, with no attacks at any other time of the cycle.

In women with menstrually related migraine, the diagnosis should only be made if the relationship between migraine and menstruation is greater than a chance association. To confirm this diagnosis, migraine attacks during the day −2 to +3 window must occur in at least 2 of 3 menstrual cycles. Relying on history to confirm the diagnosis can be misleading. Use of a 3-month diary can reveal the predictable patterns associated with menstrual migraine, aiding diagnosis and management. 

Menstrual migraine affects 20% to 25% of women with migraine in the general population, and 22% to 70% of women seen in headache clinics. In women diagnosed with menstrual migraine, their perimenstrual attacks have distinctive clinical features which include more associated symptoms, longer duration, greater severity, greater susceptibility to relapse, greater resistance to treatment, and greater disability than migraines occurring at other times during the menstrual cycle.

Symptomatic treatment of perimenstrual attacks of migraine is the same as for treatment of non-menstrual attacks, but due to the longer duration of perimenstrual attacks, treatment usually needs to be repeated on several consecutive days. With respect to prevention, specific consideration should be given to the presence of menstrual disorders, contraceptive requirements, pregnancy wishes, and symptoms of perimenopause.

The 2 established triggers for perimenstrual migraine attacks are prostaglandin release, which also results in dysmenorrhea, and late luteal phase estrogen "withdrawal". There are no investigations to identify the relevant mechanism(s). However, a history of dysmenorrhea is suggestive of a prostaglandin trigger and both migraine and dysmenorrhea can benefit from treatment with prostaglandin inhibitors.

Contraceptive methods can effectively manage both perimenstrual triggers. The European Headache Federation and the European Society of Contraception and Reproductive Health recommend combined hormonal contraception (CHC) in women with menstrual migraine who require contraception or who have additional menstrual disorders that use of CHC would benefit. The desogestrel progestogen-only pill is an alternative option, particularly for women with aura, but bleeding side effects are a common reason for discontinuation.

The principal barriers to effective management of menstrual migraine are lack of awareness and under-diagnosis. Although the IHS criteria facilitate research diagnosis, there continues to be important unmet needs in the clinical management of women with menstrual migraine. Improved awareness by healthcare professionals is critical; women visiting their primary care physician or who are referred to a gynecologist seldom mention migraine unless specifically asked.

Contraception

Most women use contraception at some stage in their lives. Hormonal contraception, particularly CHC, is popular and effective, with additional non-contraceptive benefits.

As with the natural menstrual cycle, estrogen “withdrawal” (in this case the consequence of stopping contraceptive hormones during the hormone-free interval) can trigger migraine without aura. Eliminating the hormone-free interval by taking CHCs continuously, without a break, eliminates the risk of estrogen withdrawal migraine. Further, continuous use of CHC increases contraceptive efficacy and there are no differential safety concerns.

Contraceptive use of CHC is contraindicated in women with migraine aura, since migraine aura and use of ethinylestradiol are independent risk factors for ischemic stroke. Effective contraception need not be compromised since progestogen-only and non-hormonal methods—

several of which are more effective than CHC—are not associated with increased risk.

Despite there being little concern regarding use of CHCs in women with migraine without aura, clinical experience suggests that many women with migraine are denied CHCs. In some cases, this stems from misdiagnosing premonitory migraine symptoms as aura. In other cases, even a clear diagnosis of menstrual migraine without aura can result in CHCs being withheld due to the misconception of risk. To ensure that women receive optimum contraceptive options, contraceptive providers need a better understanding of the Medical Eligibility Criteria for Contraceptive Use as well as simple tools to aid migraine diagnosis.

Pregnancy and breastfeeding

Around 60-70% of pregnant women with migraine experience fewer attacks compared to pre-pregnancy, with improvement more likely in women with a history of menstrual migraine. In contrast, migraine with aura tends to continue to occur throughout pregnancy and postpartum and may start for the first time during this period. Women can be reassured that migraine, both with or without aura, does not have any adverse effect on the outcome of pregnancy. However, women with aura should be monitored during pregnancy since there is an increased risk of comorbid conditions, such as arterial and venous thrombosis, pre-eclampsia, and gestational hypertension.

Healthcare professionals need to be aware of their female patients with migraine who may be planning to conceive so that strategies for treating migraine can be discussed. Most drugs and other teratogens exert their greatest effects on the fetus in the first trimester, often before pregnancy is confirmed. Symptomatic treatment with acetaminophen and metoclopramide is safe. If this is ineffective, sumatriptan is an option. Ergot derivatives are contraindicated. If prophylaxis is considered necessary, propranolol is the safest and most effective option. Valproate is contraindicated for migraine prophylaxis in women of reproductive capacity who are not using adequate contraception due to the increased risk of neural tube defects, cardiac defects, and other developmental effects associated with use of this medication.

Fertility treatment is frequently associated with increased headache and migraine. It is also important to consider that headache can be symptomatic of emotional stress, which would benefit from supportive management.

Breastfeeding generally maintains the benefits of pregnancy on migraine and should be encouraged, where possible. Recent studies suggest that the number of women choosing to breastfeed is rising, but there is also evidence that women with migraine do not initiate breastfeeding or discontinue because of their concerns about taking medication.

Unfortunately, many women and healthcare professionals rely on information in the package inserts, which may not tell the full story. Milk supply can reduce within 48 hours without full and repeated emptying of the breast, so advising a woman to interrupt breastfeeding for even a few days while treating a migraine attack can destroy her milk production. Hence, maintaining breastfeeding during drug treatment is increasingly recommended. Healthcare professionals should be informed about which treatments can safely be used at this time. For acute treatment, acetaminophen and NSAIDS are first-line options and can be combined with metoclopramide. Sumatriptan is a second-line option that allows breastfeeding to continue without the need to ‘pump and dump’.

Menopause and hormone replacement therapy

Despite increased prevalence of menstrual migraine during perimenopause, headache and migraine are under-reported by women with perimenopausal migraine. Management should be directed to treating the menopausal symptoms, which may include hormone replacement therapy (HRT). Studies suggest a significant association between migraine and current use of HRT.

Understanding the effects of different types of HRT is important, as some studies suggest that a history of worsening migraine at menopause is a factor in predicting worsening migraine with HRT. However, the regimen of HRT, route of estrogen, and type of progestogen all have differing effects on migraine. Non-oral routes of continuous estrogen/progestogen are less likely to have a negative effect on migraine than oral formulations, and continuous estrogen/progestogen appears to be better tolerated than cyclical combined HRT. Oral micronized progesterone may directly benefit migraine due to GABAergic effects. Disturbed sleep is both a common migraine trigger and the action of progesterone to restore normal sleep will also benefit migraine.   

In contrast to CHCs, physiologic doses of transdermal estradiol and progesterone used in HRT are not associated with increased risk of ischemic stroke and can be used by women with migraine aura.

Conclusion

Many questions related to these topics don't have ready answers—questions like increased prevalence of hormone-related migraine, age of onset of menstrual migraines, and multispecialty treatment of these patients. Research is either limited or yet to be done, and we may not get the answers until healthcare professionals and women are more aware of the hormonal effects of migraine.

The effects of hormonal changes on migraine provide physicians with specific opportunities to identify and manage migraine in women. Under-treatment – in addition to causing unnecessary disability and suffering – is not economically cost-effective in terms of time lost from work and burden placed on the families of these patients. More effective health care would alleviate much of the suffering and therefore reduce both the personal and financial costs of migraine. Ineffective management of migraine in women has significant implications for women, their families, and their employers.

Migraine affects more than 1 in 6 US adults. This figure masks the fact that migraine is a predominantly female disorder; compared with men, 3-month migraine prevalence is more than 2-fold higher (21% vs. 10%) in women. Research by the World Health Organization has established migraine as second among the world’s causes of disability, and first among women of reproductive age.  

Despite this burden of illness, migraine is often not diagnosed or treated effectively. General lifestyle advice such as maintaining a healthy weight, sleep hygiene, regular meals, regular exercise and hydration, and management of identified predisposing or triggering factors—together with optimization of symptomatic migraine treatment—can benefit all women with migraine. However, specific hormonal events such as menstruation, hormonal contraception, pregnancy, menopause, and hormone replacement therapy have variable, but often predictable, effects on the frequency and severity of migraine. At each of these life stages, there are specific opportunities to intervene and relieve migraine burden.

Menstrual migraine

Menstruation is one of the most significant risk factors for migraine, notably migraine without aura, with increased prevalence during a 5-day perimenstrual window that starts 2 days before the onset of menses and continues through the first 3 days of menstruation.

The International Headache Society (IHS) recognizes 2 types of menstrual migraine. There is menstrually related migraine, which is migraine without aura that regularly occurs on or between day −2 to +3 of menstruation (there is no day 0), with additional attacks of migraine with or without aura at other times of the cycle. There is also pure menstrual migraine, which is migraine without aura that occurs only on or between day −2 to +3, with no attacks at any other time of the cycle.

In women with menstrually related migraine, the diagnosis should only be made if the relationship between migraine and menstruation is greater than a chance association. To confirm this diagnosis, migraine attacks during the day −2 to +3 window must occur in at least 2 of 3 menstrual cycles. Relying on history to confirm the diagnosis can be misleading. Use of a 3-month diary can reveal the predictable patterns associated with menstrual migraine, aiding diagnosis and management. 

Menstrual migraine affects 20% to 25% of women with migraine in the general population, and 22% to 70% of women seen in headache clinics. In women diagnosed with menstrual migraine, their perimenstrual attacks have distinctive clinical features which include more associated symptoms, longer duration, greater severity, greater susceptibility to relapse, greater resistance to treatment, and greater disability than migraines occurring at other times during the menstrual cycle.

Symptomatic treatment of perimenstrual attacks of migraine is the same as for treatment of non-menstrual attacks, but due to the longer duration of perimenstrual attacks, treatment usually needs to be repeated on several consecutive days. With respect to prevention, specific consideration should be given to the presence of menstrual disorders, contraceptive requirements, pregnancy wishes, and symptoms of perimenopause.

The 2 established triggers for perimenstrual migraine attacks are prostaglandin release, which also results in dysmenorrhea, and late luteal phase estrogen "withdrawal". There are no investigations to identify the relevant mechanism(s). However, a history of dysmenorrhea is suggestive of a prostaglandin trigger and both migraine and dysmenorrhea can benefit from treatment with prostaglandin inhibitors.

Contraceptive methods can effectively manage both perimenstrual triggers. The European Headache Federation and the European Society of Contraception and Reproductive Health recommend combined hormonal contraception (CHC) in women with menstrual migraine who require contraception or who have additional menstrual disorders that use of CHC would benefit. The desogestrel progestogen-only pill is an alternative option, particularly for women with aura, but bleeding side effects are a common reason for discontinuation.

The principal barriers to effective management of menstrual migraine are lack of awareness and under-diagnosis. Although the IHS criteria facilitate research diagnosis, there continues to be important unmet needs in the clinical management of women with menstrual migraine. Improved awareness by healthcare professionals is critical; women visiting their primary care physician or who are referred to a gynecologist seldom mention migraine unless specifically asked.

Contraception

Most women use contraception at some stage in their lives. Hormonal contraception, particularly CHC, is popular and effective, with additional non-contraceptive benefits.

As with the natural menstrual cycle, estrogen “withdrawal” (in this case the consequence of stopping contraceptive hormones during the hormone-free interval) can trigger migraine without aura. Eliminating the hormone-free interval by taking CHCs continuously, without a break, eliminates the risk of estrogen withdrawal migraine. Further, continuous use of CHC increases contraceptive efficacy and there are no differential safety concerns.

Contraceptive use of CHC is contraindicated in women with migraine aura, since migraine aura and use of ethinylestradiol are independent risk factors for ischemic stroke. Effective contraception need not be compromised since progestogen-only and non-hormonal methods—

several of which are more effective than CHC—are not associated with increased risk.

Despite there being little concern regarding use of CHCs in women with migraine without aura, clinical experience suggests that many women with migraine are denied CHCs. In some cases, this stems from misdiagnosing premonitory migraine symptoms as aura. In other cases, even a clear diagnosis of menstrual migraine without aura can result in CHCs being withheld due to the misconception of risk. To ensure that women receive optimum contraceptive options, contraceptive providers need a better understanding of the Medical Eligibility Criteria for Contraceptive Use as well as simple tools to aid migraine diagnosis.

Pregnancy and breastfeeding

Around 60-70% of pregnant women with migraine experience fewer attacks compared to pre-pregnancy, with improvement more likely in women with a history of menstrual migraine. In contrast, migraine with aura tends to continue to occur throughout pregnancy and postpartum and may start for the first time during this period. Women can be reassured that migraine, both with or without aura, does not have any adverse effect on the outcome of pregnancy. However, women with aura should be monitored during pregnancy since there is an increased risk of comorbid conditions, such as arterial and venous thrombosis, pre-eclampsia, and gestational hypertension.

Healthcare professionals need to be aware of their female patients with migraine who may be planning to conceive so that strategies for treating migraine can be discussed. Most drugs and other teratogens exert their greatest effects on the fetus in the first trimester, often before pregnancy is confirmed. Symptomatic treatment with acetaminophen and metoclopramide is safe. If this is ineffective, sumatriptan is an option. Ergot derivatives are contraindicated. If prophylaxis is considered necessary, propranolol is the safest and most effective option. Valproate is contraindicated for migraine prophylaxis in women of reproductive capacity who are not using adequate contraception due to the increased risk of neural tube defects, cardiac defects, and other developmental effects associated with use of this medication.

Fertility treatment is frequently associated with increased headache and migraine. It is also important to consider that headache can be symptomatic of emotional stress, which would benefit from supportive management.

Breastfeeding generally maintains the benefits of pregnancy on migraine and should be encouraged, where possible. Recent studies suggest that the number of women choosing to breastfeed is rising, but there is also evidence that women with migraine do not initiate breastfeeding or discontinue because of their concerns about taking medication.

Unfortunately, many women and healthcare professionals rely on information in the package inserts, which may not tell the full story. Milk supply can reduce within 48 hours without full and repeated emptying of the breast, so advising a woman to interrupt breastfeeding for even a few days while treating a migraine attack can destroy her milk production. Hence, maintaining breastfeeding during drug treatment is increasingly recommended. Healthcare professionals should be informed about which treatments can safely be used at this time. For acute treatment, acetaminophen and NSAIDS are first-line options and can be combined with metoclopramide. Sumatriptan is a second-line option that allows breastfeeding to continue without the need to ‘pump and dump’.

Menopause and hormone replacement therapy

Despite increased prevalence of menstrual migraine during perimenopause, headache and migraine are under-reported by women with perimenopausal migraine. Management should be directed to treating the menopausal symptoms, which may include hormone replacement therapy (HRT). Studies suggest a significant association between migraine and current use of HRT.

Understanding the effects of different types of HRT is important, as some studies suggest that a history of worsening migraine at menopause is a factor in predicting worsening migraine with HRT. However, the regimen of HRT, route of estrogen, and type of progestogen all have differing effects on migraine. Non-oral routes of continuous estrogen/progestogen are less likely to have a negative effect on migraine than oral formulations, and continuous estrogen/progestogen appears to be better tolerated than cyclical combined HRT. Oral micronized progesterone may directly benefit migraine due to GABAergic effects. Disturbed sleep is both a common migraine trigger and the action of progesterone to restore normal sleep will also benefit migraine.   

In contrast to CHCs, physiologic doses of transdermal estradiol and progesterone used in HRT are not associated with increased risk of ischemic stroke and can be used by women with migraine aura.

Conclusion

Many questions related to these topics don't have ready answers—questions like increased prevalence of hormone-related migraine, age of onset of menstrual migraines, and multispecialty treatment of these patients. Research is either limited or yet to be done, and we may not get the answers until healthcare professionals and women are more aware of the hormonal effects of migraine.

The effects of hormonal changes on migraine provide physicians with specific opportunities to identify and manage migraine in women. Under-treatment – in addition to causing unnecessary disability and suffering – is not economically cost-effective in terms of time lost from work and burden placed on the families of these patients. More effective health care would alleviate much of the suffering and therefore reduce both the personal and financial costs of migraine. Ineffective management of migraine in women has significant implications for women, their families, and their employers.

Migraine affects more than 1 in 6 US adults. This figure masks the fact that migraine is a predominantly female disorder; compared with men, 3-month migraine prevalence is more than 2-fold higher (21% vs. 10%) in women. Research by the World Health Organization has established migraine as second among the world’s causes of disability, and first among women of reproductive age.  

Despite this burden of illness, migraine is often not diagnosed or treated effectively. General lifestyle advice such as maintaining a healthy weight, sleep hygiene, regular meals, regular exercise and hydration, and management of identified predisposing or triggering factors—together with optimization of symptomatic migraine treatment—can benefit all women with migraine. However, specific hormonal events such as menstruation, hormonal contraception, pregnancy, menopause, and hormone replacement therapy have variable, but often predictable, effects on the frequency and severity of migraine. At each of these life stages, there are specific opportunities to intervene and relieve migraine burden.

Menstrual migraine

Menstruation is one of the most significant risk factors for migraine, notably migraine without aura, with increased prevalence during a 5-day perimenstrual window that starts 2 days before the onset of menses and continues through the first 3 days of menstruation.

The International Headache Society (IHS) recognizes 2 types of menstrual migraine. There is menstrually related migraine, which is migraine without aura that regularly occurs on or between day −2 to +3 of menstruation (there is no day 0), with additional attacks of migraine with or without aura at other times of the cycle. There is also pure menstrual migraine, which is migraine without aura that occurs only on or between day −2 to +3, with no attacks at any other time of the cycle.

In women with menstrually related migraine, the diagnosis should only be made if the relationship between migraine and menstruation is greater than a chance association. To confirm this diagnosis, migraine attacks during the day −2 to +3 window must occur in at least 2 of 3 menstrual cycles. Relying on history to confirm the diagnosis can be misleading. Use of a 3-month diary can reveal the predictable patterns associated with menstrual migraine, aiding diagnosis and management. 

Menstrual migraine affects 20% to 25% of women with migraine in the general population, and 22% to 70% of women seen in headache clinics. In women diagnosed with menstrual migraine, their perimenstrual attacks have distinctive clinical features which include more associated symptoms, longer duration, greater severity, greater susceptibility to relapse, greater resistance to treatment, and greater disability than migraines occurring at other times during the menstrual cycle.

Symptomatic treatment of perimenstrual attacks of migraine is the same as for treatment of non-menstrual attacks, but due to the longer duration of perimenstrual attacks, treatment usually needs to be repeated on several consecutive days. With respect to prevention, specific consideration should be given to the presence of menstrual disorders, contraceptive requirements, pregnancy wishes, and symptoms of perimenopause.

The 2 established triggers for perimenstrual migraine attacks are prostaglandin release, which also results in dysmenorrhea, and late luteal phase estrogen "withdrawal". There are no investigations to identify the relevant mechanism(s). However, a history of dysmenorrhea is suggestive of a prostaglandin trigger and both migraine and dysmenorrhea can benefit from treatment with prostaglandin inhibitors.

Contraceptive methods can effectively manage both perimenstrual triggers. The European Headache Federation and the European Society of Contraception and Reproductive Health recommend combined hormonal contraception (CHC) in women with menstrual migraine who require contraception or who have additional menstrual disorders that use of CHC would benefit. The desogestrel progestogen-only pill is an alternative option, particularly for women with aura, but bleeding side effects are a common reason for discontinuation.

The principal barriers to effective management of menstrual migraine are lack of awareness and under-diagnosis. Although the IHS criteria facilitate research diagnosis, there continues to be important unmet needs in the clinical management of women with menstrual migraine. Improved awareness by healthcare professionals is critical; women visiting their primary care physician or who are referred to a gynecologist seldom mention migraine unless specifically asked.

Contraception

Most women use contraception at some stage in their lives. Hormonal contraception, particularly CHC, is popular and effective, with additional non-contraceptive benefits.

As with the natural menstrual cycle, estrogen “withdrawal” (in this case the consequence of stopping contraceptive hormones during the hormone-free interval) can trigger migraine without aura. Eliminating the hormone-free interval by taking CHCs continuously, without a break, eliminates the risk of estrogen withdrawal migraine. Further, continuous use of CHC increases contraceptive efficacy and there are no differential safety concerns.

Contraceptive use of CHC is contraindicated in women with migraine aura, since migraine aura and use of ethinylestradiol are independent risk factors for ischemic stroke. Effective contraception need not be compromised since progestogen-only and non-hormonal methods—

several of which are more effective than CHC—are not associated with increased risk.

Despite there being little concern regarding use of CHCs in women with migraine without aura, clinical experience suggests that many women with migraine are denied CHCs. In some cases, this stems from misdiagnosing premonitory migraine symptoms as aura. In other cases, even a clear diagnosis of menstrual migraine without aura can result in CHCs being withheld due to the misconception of risk. To ensure that women receive optimum contraceptive options, contraceptive providers need a better understanding of the Medical Eligibility Criteria for Contraceptive Use as well as simple tools to aid migraine diagnosis.

Pregnancy and breastfeeding

Around 60-70% of pregnant women with migraine experience fewer attacks compared to pre-pregnancy, with improvement more likely in women with a history of menstrual migraine. In contrast, migraine with aura tends to continue to occur throughout pregnancy and postpartum and may start for the first time during this period. Women can be reassured that migraine, both with or without aura, does not have any adverse effect on the outcome of pregnancy. However, women with aura should be monitored during pregnancy since there is an increased risk of comorbid conditions, such as arterial and venous thrombosis, pre-eclampsia, and gestational hypertension.

Healthcare professionals need to be aware of their female patients with migraine who may be planning to conceive so that strategies for treating migraine can be discussed. Most drugs and other teratogens exert their greatest effects on the fetus in the first trimester, often before pregnancy is confirmed. Symptomatic treatment with acetaminophen and metoclopramide is safe. If this is ineffective, sumatriptan is an option. Ergot derivatives are contraindicated. If prophylaxis is considered necessary, propranolol is the safest and most effective option. Valproate is contraindicated for migraine prophylaxis in women of reproductive capacity who are not using adequate contraception due to the increased risk of neural tube defects, cardiac defects, and other developmental effects associated with use of this medication.

Fertility treatment is frequently associated with increased headache and migraine. It is also important to consider that headache can be symptomatic of emotional stress, which would benefit from supportive management.

Breastfeeding generally maintains the benefits of pregnancy on migraine and should be encouraged, where possible. Recent studies suggest that the number of women choosing to breastfeed is rising, but there is also evidence that women with migraine do not initiate breastfeeding or discontinue because of their concerns about taking medication.

Unfortunately, many women and healthcare professionals rely on information in the package inserts, which may not tell the full story. Milk supply can reduce within 48 hours without full and repeated emptying of the breast, so advising a woman to interrupt breastfeeding for even a few days while treating a migraine attack can destroy her milk production. Hence, maintaining breastfeeding during drug treatment is increasingly recommended. Healthcare professionals should be informed about which treatments can safely be used at this time. For acute treatment, acetaminophen and NSAIDS are first-line options and can be combined with metoclopramide. Sumatriptan is a second-line option that allows breastfeeding to continue without the need to ‘pump and dump’.

Menopause and hormone replacement therapy

Despite increased prevalence of menstrual migraine during perimenopause, headache and migraine are under-reported by women with perimenopausal migraine. Management should be directed to treating the menopausal symptoms, which may include hormone replacement therapy (HRT). Studies suggest a significant association between migraine and current use of HRT.

Understanding the effects of different types of HRT is important, as some studies suggest that a history of worsening migraine at menopause is a factor in predicting worsening migraine with HRT. However, the regimen of HRT, route of estrogen, and type of progestogen all have differing effects on migraine. Non-oral routes of continuous estrogen/progestogen are less likely to have a negative effect on migraine than oral formulations, and continuous estrogen/progestogen appears to be better tolerated than cyclical combined HRT. Oral micronized progesterone may directly benefit migraine due to GABAergic effects. Disturbed sleep is both a common migraine trigger and the action of progesterone to restore normal sleep will also benefit migraine.   

In contrast to CHCs, physiologic doses of transdermal estradiol and progesterone used in HRT are not associated with increased risk of ischemic stroke and can be used by women with migraine aura.

Conclusion

Many questions related to these topics don't have ready answers—questions like increased prevalence of hormone-related migraine, age of onset of menstrual migraines, and multispecialty treatment of these patients. Research is either limited or yet to be done, and we may not get the answers until healthcare professionals and women are more aware of the hormonal effects of migraine.

The effects of hormonal changes on migraine provide physicians with specific opportunities to identify and manage migraine in women. Under-treatment – in addition to causing unnecessary disability and suffering – is not economically cost-effective in terms of time lost from work and burden placed on the families of these patients. More effective health care would alleviate much of the suffering and therefore reduce both the personal and financial costs of migraine. Ineffective management of migraine in women has significant implications for women, their families, and their employers.