On Dec. 23, 2016, the Chinese National Health and Family Planning Commission officially endorsed Pulmonary and Critical Care Medicine (PCCM) as a pilot subspecialty within China. PCCM is one of three subspecialties (together with neurosurgery and cardiology) to pioneer fellowship training education in China. With the official endorsement of PCCM, local efforts will progress within China to administer programs and extend the standards of training throughout medical education in China. PCCM certification will now become a requirement for appointment of pulmonary department chairs and for promotion within the subspecialty.

Since 2012, CHEST has worked closely with partners, such as the Chinese Thoracic Society, the Chinese Association of Chest Physicians, and the Chinese Medical Doctor Association, on the development of China’s first fellowship program offering standardized training in PCCM for Chinese physicians. As a result of these collective efforts, PCCM has now officially earned endorsement as a medical subspecialty – the first of its kind in a country where medical training typically ends after a physician completes residency training. Only a decade ago, physicians in China went directly into practice following medical school. The development of a PCCM subspecialty in China – made possible through the engagement of CHEST’s expert faculty and administration – parallels what has occurred over the past 3 decades in the United States, during which the fields of pulmonary and critical care medicine evolved into the combined subspecialty of PCCM.

The China-CHEST PCCM Fellowship Program was officially launched in 2013 with 12 participating Chinese institutions starting their PCCM training programs. By the end of 2017, 30 programs with 300 fellows and 60 faculty will be participating at institutions throughout China, with the potential to impact the care of thousands of patients. The China-PCCM Fellowship Program proudly graduated its first class of fellows in September 2016.

China-CHEST leaders, including Renli Qiao, MD, PhD, FCCP; Chen Wang, MD, PhD, FCCP; and Jack Buckley, MD, MPH, FCCP; with Steve Welch, CHEST Executive Vice President, recently participated in local site visits to provide ongoing education and support to Chinese PCCM fellowship programs. They also participated in the November 2016 Mingdao Forum in Beijing to highlight the history and achievements of the China-CHEST PCCM program.

The vast reach and clinical exposure of this program highlights how an international professional medical association like CHEST, through innovative education and strategic collaborative partnerships, is able to impact medical training both within and beyond its specialty on a global scale.

Darcy Marciniuk, MD, FCCP
Chair, China–CHEST PCCM Steering Committee
Professor of Medicine, University of Saskatchewan,
Saskatoon, SK, Canada

Renli Qiao, MD, PhD, FCCP
Medical Director, China–CHEST PCCM Program
Professor of Clinical Medicine,
Keck School of Medicine of USC,
Los Angeles, California

Robb Rabito, CHCP
Director, Education Operations CHEST
Glenview, Illinois

On Dec. 23, 2016, the Chinese National Health and Family Planning Commission officially endorsed Pulmonary and Critical Care Medicine (PCCM) as a pilot subspecialty within China. PCCM is one of three subspecialties (together with neurosurgery and cardiology) to pioneer fellowship training education in China. With the official endorsement of PCCM, local efforts will progress within China to administer programs and extend the standards of training throughout medical education in China. PCCM certification will now become a requirement for appointment of pulmonary department chairs and for promotion within the subspecialty.

Since 2012, CHEST has worked closely with partners, such as the Chinese Thoracic Society, the Chinese Association of Chest Physicians, and the Chinese Medical Doctor Association, on the development of China’s first fellowship program offering standardized training in PCCM for Chinese physicians. As a result of these collective efforts, PCCM has now officially earned endorsement as a medical subspecialty – the first of its kind in a country where medical training typically ends after a physician completes residency training. Only a decade ago, physicians in China went directly into practice following medical school. The development of a PCCM subspecialty in China – made possible through the engagement of CHEST’s expert faculty and administration – parallels what has occurred over the past 3 decades in the United States, during which the fields of pulmonary and critical care medicine evolved into the combined subspecialty of PCCM.

The China-CHEST PCCM Fellowship Program was officially launched in 2013 with 12 participating Chinese institutions starting their PCCM training programs. By the end of 2017, 30 programs with 300 fellows and 60 faculty will be participating at institutions throughout China, with the potential to impact the care of thousands of patients. The China-PCCM Fellowship Program proudly graduated its first class of fellows in September 2016.

China-CHEST leaders, including Renli Qiao, MD, PhD, FCCP; Chen Wang, MD, PhD, FCCP; and Jack Buckley, MD, MPH, FCCP; with Steve Welch, CHEST Executive Vice President, recently participated in local site visits to provide ongoing education and support to Chinese PCCM fellowship programs. They also participated in the November 2016 Mingdao Forum in Beijing to highlight the history and achievements of the China-CHEST PCCM program.

The vast reach and clinical exposure of this program highlights how an international professional medical association like CHEST, through innovative education and strategic collaborative partnerships, is able to impact medical training both within and beyond its specialty on a global scale.

Darcy Marciniuk, MD, FCCP
Chair, China–CHEST PCCM Steering Committee
Professor of Medicine, University of Saskatchewan,
Saskatoon, SK, Canada

Renli Qiao, MD, PhD, FCCP
Medical Director, China–CHEST PCCM Program
Professor of Clinical Medicine,
Keck School of Medicine of USC,
Los Angeles, California

Robb Rabito, CHCP
Director, Education Operations CHEST
Glenview, Illinois

On Dec. 23, 2016, the Chinese National Health and Family Planning Commission officially endorsed Pulmonary and Critical Care Medicine (PCCM) as a pilot subspecialty within China. PCCM is one of three subspecialties (together with neurosurgery and cardiology) to pioneer fellowship training education in China. With the official endorsement of PCCM, local efforts will progress within China to administer programs and extend the standards of training throughout medical education in China. PCCM certification will now become a requirement for appointment of pulmonary department chairs and for promotion within the subspecialty.

Since 2012, CHEST has worked closely with partners, such as the Chinese Thoracic Society, the Chinese Association of Chest Physicians, and the Chinese Medical Doctor Association, on the development of China’s first fellowship program offering standardized training in PCCM for Chinese physicians. As a result of these collective efforts, PCCM has now officially earned endorsement as a medical subspecialty – the first of its kind in a country where medical training typically ends after a physician completes residency training. Only a decade ago, physicians in China went directly into practice following medical school. The development of a PCCM subspecialty in China – made possible through the engagement of CHEST’s expert faculty and administration – parallels what has occurred over the past 3 decades in the United States, during which the fields of pulmonary and critical care medicine evolved into the combined subspecialty of PCCM.

The China-CHEST PCCM Fellowship Program was officially launched in 2013 with 12 participating Chinese institutions starting their PCCM training programs. By the end of 2017, 30 programs with 300 fellows and 60 faculty will be participating at institutions throughout China, with the potential to impact the care of thousands of patients. The China-PCCM Fellowship Program proudly graduated its first class of fellows in September 2016.

China-CHEST leaders, including Renli Qiao, MD, PhD, FCCP; Chen Wang, MD, PhD, FCCP; and Jack Buckley, MD, MPH, FCCP; with Steve Welch, CHEST Executive Vice President, recently participated in local site visits to provide ongoing education and support to Chinese PCCM fellowship programs. They also participated in the November 2016 Mingdao Forum in Beijing to highlight the history and achievements of the China-CHEST PCCM program.

The vast reach and clinical exposure of this program highlights how an international professional medical association like CHEST, through innovative education and strategic collaborative partnerships, is able to impact medical training both within and beyond its specialty on a global scale.

Darcy Marciniuk, MD, FCCP
Chair, China–CHEST PCCM Steering Committee
Professor of Medicine, University of Saskatchewan,
Saskatoon, SK, Canada

Renli Qiao, MD, PhD, FCCP
Medical Director, China–CHEST PCCM Program
Professor of Clinical Medicine,
Keck School of Medicine of USC,
Los Angeles, California

Robb Rabito, CHCP
Director, Education Operations CHEST
Glenview, Illinois

Overutilization of tests, treatments, and procedures is an important example of low-value care that adds to the high cost of health care and provides little to no benefit for patients. To combat this problem, the American Board of Internal Medicine Foundation developed the Choosing Wisely Campaign, tasking professional societies to develop lists of the top five medical services that patients should question.

The Critical Care Societies Collaborative (CCSC), which comprises the four major U.S. professional and scientific societies – the American Association of Critical-Care Nurses, the American College of Chest Physicians, the American Thoracic Society, and the Society of Critical Care Medicine – participated by creating a task force that addressed this task to focus on critical care delivery.

Five CCSC recommendations were formulated:

1. Don’t order diagnostic tests at regular intervals (such as every day), but rather in response to specific clinical questions.

2. Don’t transfuse red blood cells in hemodynamically stable, nonbleeding patients with a hemoglobin concentration greater than 7 mg/dL.

3. Don’t use parenteral nutrition in adequately nourished critically ill patients within the first 7 days of an ICU stay.

4. Don’t deeply sedate mechanically ventilated patients without a specific indication and without daily attempts to lighten sedation.

5. Don’t continue life support for patients at high risk for death or severely impaired functional recovery without offering patients and their families the alternative of care focused entirely on comfort.

The CCSC is tracking use/implementation of the Choosing Wisely recommendations among its four member organizations. Please complete this short survey at https://redcap.rush.edu/redcap/surveys/?s. Please click submit when finished.

Overutilization of tests, treatments, and procedures is an important example of low-value care that adds to the high cost of health care and provides little to no benefit for patients. To combat this problem, the American Board of Internal Medicine Foundation developed the Choosing Wisely Campaign, tasking professional societies to develop lists of the top five medical services that patients should question.

The Critical Care Societies Collaborative (CCSC), which comprises the four major U.S. professional and scientific societies – the American Association of Critical-Care Nurses, the American College of Chest Physicians, the American Thoracic Society, and the Society of Critical Care Medicine – participated by creating a task force that addressed this task to focus on critical care delivery.

Five CCSC recommendations were formulated:

1. Don’t order diagnostic tests at regular intervals (such as every day), but rather in response to specific clinical questions.

2. Don’t transfuse red blood cells in hemodynamically stable, nonbleeding patients with a hemoglobin concentration greater than 7 mg/dL.

3. Don’t use parenteral nutrition in adequately nourished critically ill patients within the first 7 days of an ICU stay.

4. Don’t deeply sedate mechanically ventilated patients without a specific indication and without daily attempts to lighten sedation.

5. Don’t continue life support for patients at high risk for death or severely impaired functional recovery without offering patients and their families the alternative of care focused entirely on comfort.

The CCSC is tracking use/implementation of the Choosing Wisely recommendations among its four member organizations. Please complete this short survey at https://redcap.rush.edu/redcap/surveys/?s. Please click submit when finished.

Overutilization of tests, treatments, and procedures is an important example of low-value care that adds to the high cost of health care and provides little to no benefit for patients. To combat this problem, the American Board of Internal Medicine Foundation developed the Choosing Wisely Campaign, tasking professional societies to develop lists of the top five medical services that patients should question.

The Critical Care Societies Collaborative (CCSC), which comprises the four major U.S. professional and scientific societies – the American Association of Critical-Care Nurses, the American College of Chest Physicians, the American Thoracic Society, and the Society of Critical Care Medicine – participated by creating a task force that addressed this task to focus on critical care delivery.

Five CCSC recommendations were formulated:

1. Don’t order diagnostic tests at regular intervals (such as every day), but rather in response to specific clinical questions.

2. Don’t transfuse red blood cells in hemodynamically stable, nonbleeding patients with a hemoglobin concentration greater than 7 mg/dL.

3. Don’t use parenteral nutrition in adequately nourished critically ill patients within the first 7 days of an ICU stay.

4. Don’t deeply sedate mechanically ventilated patients without a specific indication and without daily attempts to lighten sedation.

5. Don’t continue life support for patients at high risk for death or severely impaired functional recovery without offering patients and their families the alternative of care focused entirely on comfort.

The CCSC is tracking use/implementation of the Choosing Wisely recommendations among its four member organizations. Please complete this short survey at https://redcap.rush.edu/redcap/surveys/?s. Please click submit when finished.

Every year, the CHEST Foundation awards more than a half-million dollars in grants to the next generation of lung health champions. February 2017 marks the start of the foundation’s next grant cycle, and we are excited to announce a new clinical research grant in Cystic Fibrosis, among many other disease-state topics. In 2016, the foundation awarded 11 CHEST members for their innovative and inspiring research proposals and community service programs.

“I am very proud to have been awarded a CHEST Foundation grant and pleased that clinical research and real-world evidence are a priority to the foundation,” stated Alice Turner, MBChB, PhD. Dr. Turner was awarded the 2016 CHEST Foundation and the Alpha-1 Foundation Clinical Research Grant in Alpha-1 Antitrypsin Deficiency. “This award means that my patients can now see publicly the efforts that are being made to reduce inequities in care and ensure that the best treatments are made available in the UK.”

Every year, the CHEST Foundation awards more than a half-million dollars in grants to the next generation of lung health champions. February 2017 marks the start of the foundation’s next grant cycle, and we are excited to announce a new clinical research grant in Cystic Fibrosis, among many other disease-state topics. In 2016, the foundation awarded 11 CHEST members for their innovative and inspiring research proposals and community service programs.

“I am very proud to have been awarded a CHEST Foundation grant and pleased that clinical research and real-world evidence are a priority to the foundation,” stated Alice Turner, MBChB, PhD. Dr. Turner was awarded the 2016 CHEST Foundation and the Alpha-1 Foundation Clinical Research Grant in Alpha-1 Antitrypsin Deficiency. “This award means that my patients can now see publicly the efforts that are being made to reduce inequities in care and ensure that the best treatments are made available in the UK.”

Every year, the CHEST Foundation awards more than a half-million dollars in grants to the next generation of lung health champions. February 2017 marks the start of the foundation’s next grant cycle, and we are excited to announce a new clinical research grant in Cystic Fibrosis, among many other disease-state topics. In 2016, the foundation awarded 11 CHEST members for their innovative and inspiring research proposals and community service programs.

“I am very proud to have been awarded a CHEST Foundation grant and pleased that clinical research and real-world evidence are a priority to the foundation,” stated Alice Turner, MBChB, PhD. Dr. Turner was awarded the 2016 CHEST Foundation and the Alpha-1 Foundation Clinical Research Grant in Alpha-1 Antitrypsin Deficiency. “This award means that my patients can now see publicly the efforts that are being made to reduce inequities in care and ensure that the best treatments are made available in the UK.”

Editorial

GOLD 2017: A New Report
By Dr. P. J. Barnes

Original Research

Long-term Outcomes of Patients With Ground-Glass Opacities Detected Using CT Scanning. By Dr. S. Sawada, et al.

ICU Telemedicine Program Financial Outcomes. By Dr. C. M. Lilly et al.

Accuracy of Lung Ultrasonography in the Diagnosis of Pneumonia in Adults: Systematic Review and Meta-Analysis. By Dr. A. M. Llamas-Álvarez, et al.

Evidence-based Medicine

Cough in the Athlete: CHEST Guideline and Expert Panel Report. By Dr. L-P Boulet, et al, on behalf of the CHEST Expert Cough Panel.

Editorial

GOLD 2017: A New Report
By Dr. P. J. Barnes

Original Research

Long-term Outcomes of Patients With Ground-Glass Opacities Detected Using CT Scanning. By Dr. S. Sawada, et al.

ICU Telemedicine Program Financial Outcomes. By Dr. C. M. Lilly et al.

Accuracy of Lung Ultrasonography in the Diagnosis of Pneumonia in Adults: Systematic Review and Meta-Analysis. By Dr. A. M. Llamas-Álvarez, et al.

Evidence-based Medicine

Cough in the Athlete: CHEST Guideline and Expert Panel Report. By Dr. L-P Boulet, et al, on behalf of the CHEST Expert Cough Panel.

Editorial

GOLD 2017: A New Report
By Dr. P. J. Barnes

Original Research

Long-term Outcomes of Patients With Ground-Glass Opacities Detected Using CT Scanning. By Dr. S. Sawada, et al.

ICU Telemedicine Program Financial Outcomes. By Dr. C. M. Lilly et al.

Accuracy of Lung Ultrasonography in the Diagnosis of Pneumonia in Adults: Systematic Review and Meta-Analysis. By Dr. A. M. Llamas-Álvarez, et al.

Evidence-based Medicine

Cough in the Athlete: CHEST Guideline and Expert Panel Report. By Dr. L-P Boulet, et al, on behalf of the CHEST Expert Cough Panel.

Clayton T. Cowl, MD, FCCP, is the CHEST President-Designate and sits as a member of the Board of Regents. Dr. Cowl’s presidential term will be 2018-2019. He currently is the Chair of the Division of Preventive, Occupational, and Aerospace Medicine with a joint appointment in the Division of Pulmonary and Critical Care Medicine at Mayo Clinic in Rochester, Minnesota.

Dr. Cowl is triple board-certified in Pulmonary and Critical Care Medicine, Occupational Medicine, and Internal Medicine, with an interest in airway disorders, occupational-related respiratory health, toxicology, altitude physiology, and transportation medicine.

His research focus has included projects in altitude physiology at Mayo Clinic’s altitude chamber and testing for the emergency oxygen passenger mask in the Boeing 787 airliner. He has also published in the areas of occupational asthma and toxic inhalations.

Clayton T. Cowl, MD, FCCP, is the CHEST President-Designate and sits as a member of the Board of Regents. Dr. Cowl’s presidential term will be 2018-2019. He currently is the Chair of the Division of Preventive, Occupational, and Aerospace Medicine with a joint appointment in the Division of Pulmonary and Critical Care Medicine at Mayo Clinic in Rochester, Minnesota.

Dr. Cowl is triple board-certified in Pulmonary and Critical Care Medicine, Occupational Medicine, and Internal Medicine, with an interest in airway disorders, occupational-related respiratory health, toxicology, altitude physiology, and transportation medicine.

His research focus has included projects in altitude physiology at Mayo Clinic’s altitude chamber and testing for the emergency oxygen passenger mask in the Boeing 787 airliner. He has also published in the areas of occupational asthma and toxic inhalations.

Clayton T. Cowl, MD, FCCP, is the CHEST President-Designate and sits as a member of the Board of Regents. Dr. Cowl’s presidential term will be 2018-2019. He currently is the Chair of the Division of Preventive, Occupational, and Aerospace Medicine with a joint appointment in the Division of Pulmonary and Critical Care Medicine at Mayo Clinic in Rochester, Minnesota.

Dr. Cowl is triple board-certified in Pulmonary and Critical Care Medicine, Occupational Medicine, and Internal Medicine, with an interest in airway disorders, occupational-related respiratory health, toxicology, altitude physiology, and transportation medicine.

His research focus has included projects in altitude physiology at Mayo Clinic’s altitude chamber and testing for the emergency oxygen passenger mask in the Boeing 787 airliner. He has also published in the areas of occupational asthma and toxic inhalations.

Civil rights for the lesbian, gay, bisexual, and transgender population have advanced markedly in the past decade, and the medical community has gradually begun to address more of their health concerns. More recently, media attention to transgender individuals has encouraged many more to openly seek care.^1,2

It is estimated that anywhere from 0.3% to 5% of the US population identifies as transgender.^1-3 While awareness of this population has slowly increased, there is a paucity of research on the hormone treatment that is often essential to patients’ well-being. Studies of surgical options for transgender patients have been minimal, as well.

Primary care providers are uniquely positioned to coordinate medical services and ensure continuity of care for transgender patients as they strive to become their authentic selves. Our goal in writing this article is to equip you with the tools to provide this patient population with sensitive, high-quality care (see Table 1).^4-7 Our focus is on the diagnosis of gender dysphoria (GD) and its medical and hormonal management—the realm of primary care providers. We briefly discuss surgical management of GD, as well.

UNDERSTANDING AND DIAGNOSING GENDER DYSPHORIA

Two classification systems are used for diagnoses related to GD: the Diagnostic and Statistical Manual of Mental Disorders, Fifth Ed (DSM-5)⁸ and the International Classification of Diseases, 10th Rev (ICD-10).⁹

ICD-10 criteria use the term gender identity disorder; DSM-5 refers to gender dysphoria instead. It is important to emphasize that these classification systems represent an attempt to categorize a group of signs and symptoms that lead to distress for the patient and are not meant to suggest that being transgender is pathological. In fact, in DSM-5—released in 2013—the American Psychiatric Association revised the terminology to emphasize that such individuals are not “disordered” by the nature of their identity, but rather by the distress that being transgender causes.⁸

For a diagnosis of GD in children, DSM-5 criteria include characteristics perceived to be incongruent between the child’s sex at birth and the self-identified gender based on preferred activities or dislike of his or her own sexual anatomy. The child must meet six or more of the following for at least six months

• A repeatedly stated desire to be, or insistence that he or she is, of the other gender
• In boys, a preference for cross-dressing or simulating female attire; in girls, insistence on wearing only stereotypical masculine clothing
• Strong and persistent preferences for cross-gender roles in make-believe play or fantasy
• A strong rejection of toys/games typically associated with the child’s sex
• Intense desire to participate in stereotypical games and pastimes of the other gender
• Strong preference for playmates of the other gender
• A strong dislike of one’s sexual anatomy
• A strong desire for the primary (eg, penis or vagina) or secondary (eg, menstruation) sex characteristics of the other gender.⁸

Adolescents and adults must meet two or more of the following for at least six months

• A noticeable incongruence between the gender that the patient sees themselves as and their sex characteristics
• An intense need to do away with (or prevent) his or her primary or secondary sex features
• An intense desire to have the primary and/or secondary sex features of the other gender
• A deep desire to transform into another gender
• A profound need for society to treat them as someone of the other gender
• A powerful assurance of having the characteristic feelings and responses of the other gender.⁸

For children as well as adolescents and adults, the condition should cause the patient significant distress or significantly affect him or her socially, at work or school, and in other important areas of life.⁸

Is the patient a candidate for hormone therapy?

Two primary sources—Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7, issued by the World Professional Association for Transgender Health (WPATH)¹⁰ and Endocrine Treatment of Transsexual Persons¹¹ by the Endocrine Society—offer clinical practice guidance based on evidence and expert opinion.

WPATH recommends that a mental health professional (MHP) experienced in transgender care diagnose GD to ensure that it is not mistaken for a psychiatric condition manifesting as altered gender identity. However, if no one with such experience is available or accessible in the region, it is reasonable for a primary care provider to make the diagnosis and consider initiating hormone therapy without a mental health referral,¹² as the expected benefits outweigh the risks of nontreatment.¹³

Whether or not an MHP confirms a diagnosis of GD, it is still up to the treating provider to confirm the patient’s eligibility and readiness for hormone therapy: He or she should meet DSM-5 or ICD-10 criteria for GD, have no psychiatric comorbidity (eg, schizophrenia, body dysmorphic disorder, or uncontrolled bipolar disorder) likely to interfere with treatment, understand the expected outcomes and the social benefits and risks, and have indicated a willingness to take the hormones responsibly.

Historically, patients were required to have a documented real-life experience, defined as having fully adopted the new gender role in everyday life for at least three months.^10,11 This model has fallen out of favor, however, as it is unsupported by evidence and may place transgender individuals at physical and emotional risk. Instead, readiness is confirmed by obtaining informed consent.¹²

Puberty may be suppressed with a gonadotropin-releasing hormone (GnRH) agonist in adolescents who have a GD diagnosis and are at Tanner stage 2 to 3 of puberty until age 16. At that point, hormone therapy consistent with their gender identification may be initiated (see “How to Help Transgender Teens”).¹¹

Beginning the transition

The transitioning process is a complex and individualized journey that can include inward or outward change, or both.

For patients interested in medical interventions, possible therapies include cross-sex hormone administration and gender-affirming surgery. Both are aimed at making the physical and the psychologic more congruent. Hormone treatment (see Table 2) is often essential to reduce the distress of individuals with GD and to help them feel comfortable in their own body.^10,11,21 Psychologic conditions, such as depression, tend to improve as the transitioning process gets underway.²²

FEMALE-TO-MALE TRANSITION

CASE 1 Jennie R, a 55-year-old postmenopausal patient, comes to your office for an annual exam. Although you’ve been her primary care provider for several years, she confides for the first time that she has never been comfortable as a woman. “I’ve always felt that my body didn’t belong to me,” the patient admits, and goes on to say that for the past several years she has been living as a man. Jennie R says she is ready to start hormone therapy to assist with the gender transition and asks about the process, the benefits and risks, and how quickly she can expect to achieve the desired results.

If Jennie R were your patient, how would you respond?

Masculinizing hormone treatment

As you would explain to a patient like Jennie R, the goal of hormone therapy is to suppress the effects of the sex assigned at birth and replace them with those of the desired gender. In the case of a female transitioning to a male (known as a transman), masculinizing hormones would promote growth of facial and body hair, cessation of menses, increased muscle mass, deepening of the voice, and clitoral enlargement.^11,23,24

Physical changes induced by masculinizing hormone therapy have an expected onset of one to six months and achieve maximum effect in approximately two to five years.^10,11 Although there have been no controlled clinical trials evaluating the safety or efficacy of any transitional hormone regimen, WPATH and the Center of Excellence for Transgender Health at the University of California, San Francisco, suggest initiating intramuscular or transdermal testosterone at increasing doses until normal physiologic male testosterone levels between 350 and 700 ng/dL are achieved, or until cessation of menses.^13,25-28 The dose at which either, or both, occur should be continued as long-term maintenance therapy. Medroxyprogesterone can be added, if necessary for menstrual cessation, and a GnRH agonist or endometrial ablation can be used for refractory uterine bleeding.^29,30

Testosterone is not a contraceptive. It is important to emphasize to transmen like Jennie that they remain at risk for pregnancy if they are having sex with fertile males. Caution patients not to assume that the possibility of pregnancy ends when menses stop.

Treat minor adverse effects. Adverse effects of masculinizing hormones include vaginal atrophy, fat redistribution and weight gain, polycythemia, acne, scalp hair loss, sleep apnea, elevated liver enzymes, hyperlipidemia, cardiovascular disease, diabetes, and bone density loss. Increased risk for cancer of the female organs has not been proven.^10,11 It is reasonable to treat minor adverse effects after reviewing the risks/benefits of doing so, as discontinuing hormone therapy could be detrimental to the well-being of transitioning patients.¹¹

There are absolute contraindications to masculinizing hormone therapy, however, including pregnancy, unstable coronary artery disease, and untreated polycythemia with a hematocrit > 55%.¹⁰

Monitoring is essential. Patients receiving masculinizing hormone therapy should be monitored every three months during the first year and once or twice a year there­after, with a focused history (including mood symptoms), physical exam (including weight and blood pressure), and labs (including complete blood count, liver function, renal function, and lipids) at each visit.^11,23 Some clinicians also check estradiol levels until they fall below 50 pg/mL,^23,27 while others take the cessation of uterine bleeding for > 6 months as an indicator of estrogen ­suppression.

Preventive health measures continue. Routine screening should continue, based on the patient’s assigned sex at birth. Thus, a transman who has not had a hysterectomy still needs Pap smears, mammograms if the patient has not had a double mastectomy, and bone mineral density (BMD) testing to screen for osteoporosis.^31,32 Some experts recommend starting to test BMD at age 50 for patients receiving masculinizing hormones, given the unknown effect of testosterone on bone density.^11,31,32

CASE 1 The first question for a transgender patient is about his or her current gender identity, but Jennie R has already reported living as a man. So you start by asking “What name do you prefer to use?” and “Do you prefer to be referred to with male or female pronouns?”

The patient tells you that he sees himself as a man, he wants to be called Jeff, and he prefers male pronouns. You explain that you believe he has gender dysphoria and would benefit from hormone therapy, but it is important to confirm this diagnosis with an MHP. You explain that testosterone can be prescribed for masculinizing effects, and describe the expected effects—more facial and body hair, a deeper voice, and greater muscle mass, among others—and review the likely time frame.

You also discuss the risks of masculinizing hormones (hyperlipidemia, cardiovascular disease, diabetes, and loss of bone density) that will need to be monitored. Before he leaves, you give him the name of an MHP who is experienced in transgender care and tell him to make a follow-up appointment with you after he has seen her. At the conclusion of the visit, you make a note of the patient’s name and gender identity in the chart and inform the staff of the changes.

MALE-TO-FEMALE TRANSITION

CASE 2 Before heading into your office to talk to a new patient named Carl S, you glance at his chart and see that he is a healthy 21-year-old who has come in for a routine physical. When you enter the room, you find Carl wearing a dress, heels, and make-up. After confirming that you have the right patient, you ask, “What is your current gender identity?” “Female,” says Carl, who indicates that she now goes by Carol. The patient has no medical problems, surgical history, or significant family history but reports that she has been taking spironolactone and estrogen for the past three years. Carol also says she has a new female partner and is having unprotected sexual activity.

Feminizing hormone treatment

The desired effects of feminizing hormones include voice change, decreased hair growth, breast growth, body fat redistribution, decreased muscle mass, skin softening, decreased oiliness of skin and hair, and a decrease in spontaneous erections, testicular volume, and sperm production.^10,11 The onset of feminizing effects ranges from one month to one year and the expected maximum effect occurs anywhere between three months and five years.^10,11 Regimens usually include anti-androgen agents and estrogen.^13,26-28

The medications that have been most studied with anti-androgenic effects include spironolactone and 5-α reductase inhibitors (5-ARIs) such as finasteride. Spironolactone inhibits testosterone secretion and inhibits androgen binding to androgen receptors; 5-ARIs block the conversion of testosterone to 5-α-dihydrotestosterone, the more active form.

Estrogen can be administered via oral, sublingual, transdermal, or intramuscular route, but parenteral formulations are preferred to avoid first-pass metabolism. The serum estradiol target is similar to the mean daily level of premenopausal women (< 200 pg/mL) and the level of testosterone should be in the normal female range (< 55 ng/dL).^13,26-28

The selection of medications should be individualized for each patient. Comorbidities must be considered, as well as the risk for adverse effects, which include venous thromboembolism, elevated liver enzymes, breast cancer, cardiovascular disease, diabetes, hyperprolactinemia, weight gain, gallstones, cerebrovascular disease, and severe migraine headaches.^10,11 Estrogen therapy is not reported to induce hypertrophy or premalignant changes in the prostate.³³ As is the case for masculinizing hormones, feminizing hormone therapy should be continued indefinitely for long-term effects.

Frequent monitoring is recommended. Patients taking feminizing hormones (transwomen) should be seen every two to three months in the first year and monitored once or twice a year thereafter. Serum testosterone and estradiol levels should initially be monitored every three months; serum electrolytes, specifically potassium, should be monitored every two to three months in the first year until stable.

CASE 2 You recommend that Carol S be screened annually for sexually transmitted diseases, as you would for any 21-year-old patient. You point out, too, that while estrogen and androgen-suppressing therapy decrease sperm production, there is a possibility that the patient could impregnate a female partner and recommend that contraception be used if the couple is not trying to conceive.

You also discuss the risks and benefits of hormone therapy and reasonable expectations of continued treatment. You ask Carol to schedule a follow-up visit in six months, as her hormone regimen is stable. Finally, if the patient remains on hormone therapy, you mention that the only screening unique to men transitioning to women is for breast cancer, which should begin at age 40 to 50 (as it should for all women).

Gender-affirming surgical options

Surgical management of transgender patients is not within the scope of family medicine. But it is essential to know what procedures are available, as you may have occasion to advocate for patients during the surgical referral process and possibly to provide postoperative care.

For transmen, surgical options include chest reconstruction, hysterectomy/oophorectomy, metoidioplasty (using the clitoris to surgically approximate a penis), phalloplasty, scrotoplasty, urethroplasty, and vaginectomy.^10,34 The surgeries available for transwomen are orchiectomy, vaginoplasty, penectomy, breast augmentation, thyroid chondroplasty and voice surgery, and facial feminization.^10,34 Keep in mind that not all transgender individuals desire surgery as part of the transitioning process.
 

The authors would like to acknowledge the assistance of Michelle Forcier, MD, MPH, and Karen S. Bernstein, MD, MPH, in the preparation of this manuscript.

Civil rights for the lesbian, gay, bisexual, and transgender population have advanced markedly in the past decade, and the medical community has gradually begun to address more of their health concerns. More recently, media attention to transgender individuals has encouraged many more to openly seek care.^1,2

It is estimated that anywhere from 0.3% to 5% of the US population identifies as transgender.^1-3 While awareness of this population has slowly increased, there is a paucity of research on the hormone treatment that is often essential to patients’ well-being. Studies of surgical options for transgender patients have been minimal, as well.

Primary care providers are uniquely positioned to coordinate medical services and ensure continuity of care for transgender patients as they strive to become their authentic selves. Our goal in writing this article is to equip you with the tools to provide this patient population with sensitive, high-quality care (see Table 1).^4-7 Our focus is on the diagnosis of gender dysphoria (GD) and its medical and hormonal management—the realm of primary care providers. We briefly discuss surgical management of GD, as well.

UNDERSTANDING AND DIAGNOSING GENDER DYSPHORIA

Two classification systems are used for diagnoses related to GD: the Diagnostic and Statistical Manual of Mental Disorders, Fifth Ed (DSM-5)⁸ and the International Classification of Diseases, 10th Rev (ICD-10).⁹

ICD-10 criteria use the term gender identity disorder; DSM-5 refers to gender dysphoria instead. It is important to emphasize that these classification systems represent an attempt to categorize a group of signs and symptoms that lead to distress for the patient and are not meant to suggest that being transgender is pathological. In fact, in DSM-5—released in 2013—the American Psychiatric Association revised the terminology to emphasize that such individuals are not “disordered” by the nature of their identity, but rather by the distress that being transgender causes.⁸

For a diagnosis of GD in children, DSM-5 criteria include characteristics perceived to be incongruent between the child’s sex at birth and the self-identified gender based on preferred activities or dislike of his or her own sexual anatomy. The child must meet six or more of the following for at least six months

• A repeatedly stated desire to be, or insistence that he or she is, of the other gender
• In boys, a preference for cross-dressing or simulating female attire; in girls, insistence on wearing only stereotypical masculine clothing
• Strong and persistent preferences for cross-gender roles in make-believe play or fantasy
• A strong rejection of toys/games typically associated with the child’s sex
• Intense desire to participate in stereotypical games and pastimes of the other gender
• Strong preference for playmates of the other gender
• A strong dislike of one’s sexual anatomy
• A strong desire for the primary (eg, penis or vagina) or secondary (eg, menstruation) sex characteristics of the other gender.⁸

Adolescents and adults must meet two or more of the following for at least six months

• A noticeable incongruence between the gender that the patient sees themselves as and their sex characteristics
• An intense need to do away with (or prevent) his or her primary or secondary sex features
• An intense desire to have the primary and/or secondary sex features of the other gender
• A deep desire to transform into another gender
• A profound need for society to treat them as someone of the other gender
• A powerful assurance of having the characteristic feelings and responses of the other gender.⁸

For children as well as adolescents and adults, the condition should cause the patient significant distress or significantly affect him or her socially, at work or school, and in other important areas of life.⁸

Is the patient a candidate for hormone therapy?

Two primary sources—Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7, issued by the World Professional Association for Transgender Health (WPATH)¹⁰ and Endocrine Treatment of Transsexual Persons¹¹ by the Endocrine Society—offer clinical practice guidance based on evidence and expert opinion.

WPATH recommends that a mental health professional (MHP) experienced in transgender care diagnose GD to ensure that it is not mistaken for a psychiatric condition manifesting as altered gender identity. However, if no one with such experience is available or accessible in the region, it is reasonable for a primary care provider to make the diagnosis and consider initiating hormone therapy without a mental health referral,¹² as the expected benefits outweigh the risks of nontreatment.¹³

Whether or not an MHP confirms a diagnosis of GD, it is still up to the treating provider to confirm the patient’s eligibility and readiness for hormone therapy: He or she should meet DSM-5 or ICD-10 criteria for GD, have no psychiatric comorbidity (eg, schizophrenia, body dysmorphic disorder, or uncontrolled bipolar disorder) likely to interfere with treatment, understand the expected outcomes and the social benefits and risks, and have indicated a willingness to take the hormones responsibly.

Historically, patients were required to have a documented real-life experience, defined as having fully adopted the new gender role in everyday life for at least three months.^10,11 This model has fallen out of favor, however, as it is unsupported by evidence and may place transgender individuals at physical and emotional risk. Instead, readiness is confirmed by obtaining informed consent.¹²

Puberty may be suppressed with a gonadotropin-releasing hormone (GnRH) agonist in adolescents who have a GD diagnosis and are at Tanner stage 2 to 3 of puberty until age 16. At that point, hormone therapy consistent with their gender identification may be initiated (see “How to Help Transgender Teens”).¹¹

Beginning the transition

The transitioning process is a complex and individualized journey that can include inward or outward change, or both.

For patients interested in medical interventions, possible therapies include cross-sex hormone administration and gender-affirming surgery. Both are aimed at making the physical and the psychologic more congruent. Hormone treatment (see Table 2) is often essential to reduce the distress of individuals with GD and to help them feel comfortable in their own body.^10,11,21 Psychologic conditions, such as depression, tend to improve as the transitioning process gets underway.²²

FEMALE-TO-MALE TRANSITION

CASE 1 Jennie R, a 55-year-old postmenopausal patient, comes to your office for an annual exam. Although you’ve been her primary care provider for several years, she confides for the first time that she has never been comfortable as a woman. “I’ve always felt that my body didn’t belong to me,” the patient admits, and goes on to say that for the past several years she has been living as a man. Jennie R says she is ready to start hormone therapy to assist with the gender transition and asks about the process, the benefits and risks, and how quickly she can expect to achieve the desired results.

If Jennie R were your patient, how would you respond?

Masculinizing hormone treatment

As you would explain to a patient like Jennie R, the goal of hormone therapy is to suppress the effects of the sex assigned at birth and replace them with those of the desired gender. In the case of a female transitioning to a male (known as a transman), masculinizing hormones would promote growth of facial and body hair, cessation of menses, increased muscle mass, deepening of the voice, and clitoral enlargement.^11,23,24

Physical changes induced by masculinizing hormone therapy have an expected onset of one to six months and achieve maximum effect in approximately two to five years.^10,11 Although there have been no controlled clinical trials evaluating the safety or efficacy of any transitional hormone regimen, WPATH and the Center of Excellence for Transgender Health at the University of California, San Francisco, suggest initiating intramuscular or transdermal testosterone at increasing doses until normal physiologic male testosterone levels between 350 and 700 ng/dL are achieved, or until cessation of menses.^13,25-28 The dose at which either, or both, occur should be continued as long-term maintenance therapy. Medroxyprogesterone can be added, if necessary for menstrual cessation, and a GnRH agonist or endometrial ablation can be used for refractory uterine bleeding.^29,30

Testosterone is not a contraceptive. It is important to emphasize to transmen like Jennie that they remain at risk for pregnancy if they are having sex with fertile males. Caution patients not to assume that the possibility of pregnancy ends when menses stop.

Treat minor adverse effects. Adverse effects of masculinizing hormones include vaginal atrophy, fat redistribution and weight gain, polycythemia, acne, scalp hair loss, sleep apnea, elevated liver enzymes, hyperlipidemia, cardiovascular disease, diabetes, and bone density loss. Increased risk for cancer of the female organs has not been proven.^10,11 It is reasonable to treat minor adverse effects after reviewing the risks/benefits of doing so, as discontinuing hormone therapy could be detrimental to the well-being of transitioning patients.¹¹

There are absolute contraindications to masculinizing hormone therapy, however, including pregnancy, unstable coronary artery disease, and untreated polycythemia with a hematocrit > 55%.¹⁰

Monitoring is essential. Patients receiving masculinizing hormone therapy should be monitored every three months during the first year and once or twice a year there­after, with a focused history (including mood symptoms), physical exam (including weight and blood pressure), and labs (including complete blood count, liver function, renal function, and lipids) at each visit.^11,23 Some clinicians also check estradiol levels until they fall below 50 pg/mL,^23,27 while others take the cessation of uterine bleeding for > 6 months as an indicator of estrogen ­suppression.

Preventive health measures continue. Routine screening should continue, based on the patient’s assigned sex at birth. Thus, a transman who has not had a hysterectomy still needs Pap smears, mammograms if the patient has not had a double mastectomy, and bone mineral density (BMD) testing to screen for osteoporosis.^31,32 Some experts recommend starting to test BMD at age 50 for patients receiving masculinizing hormones, given the unknown effect of testosterone on bone density.^11,31,32

CASE 1 The first question for a transgender patient is about his or her current gender identity, but Jennie R has already reported living as a man. So you start by asking “What name do you prefer to use?” and “Do you prefer to be referred to with male or female pronouns?”

The patient tells you that he sees himself as a man, he wants to be called Jeff, and he prefers male pronouns. You explain that you believe he has gender dysphoria and would benefit from hormone therapy, but it is important to confirm this diagnosis with an MHP. You explain that testosterone can be prescribed for masculinizing effects, and describe the expected effects—more facial and body hair, a deeper voice, and greater muscle mass, among others—and review the likely time frame.

You also discuss the risks of masculinizing hormones (hyperlipidemia, cardiovascular disease, diabetes, and loss of bone density) that will need to be monitored. Before he leaves, you give him the name of an MHP who is experienced in transgender care and tell him to make a follow-up appointment with you after he has seen her. At the conclusion of the visit, you make a note of the patient’s name and gender identity in the chart and inform the staff of the changes.

MALE-TO-FEMALE TRANSITION

CASE 2 Before heading into your office to talk to a new patient named Carl S, you glance at his chart and see that he is a healthy 21-year-old who has come in for a routine physical. When you enter the room, you find Carl wearing a dress, heels, and make-up. After confirming that you have the right patient, you ask, “What is your current gender identity?” “Female,” says Carl, who indicates that she now goes by Carol. The patient has no medical problems, surgical history, or significant family history but reports that she has been taking spironolactone and estrogen for the past three years. Carol also says she has a new female partner and is having unprotected sexual activity.

Feminizing hormone treatment

The desired effects of feminizing hormones include voice change, decreased hair growth, breast growth, body fat redistribution, decreased muscle mass, skin softening, decreased oiliness of skin and hair, and a decrease in spontaneous erections, testicular volume, and sperm production.^10,11 The onset of feminizing effects ranges from one month to one year and the expected maximum effect occurs anywhere between three months and five years.^10,11 Regimens usually include anti-androgen agents and estrogen.^13,26-28

The medications that have been most studied with anti-androgenic effects include spironolactone and 5-α reductase inhibitors (5-ARIs) such as finasteride. Spironolactone inhibits testosterone secretion and inhibits androgen binding to androgen receptors; 5-ARIs block the conversion of testosterone to 5-α-dihydrotestosterone, the more active form.

Estrogen can be administered via oral, sublingual, transdermal, or intramuscular route, but parenteral formulations are preferred to avoid first-pass metabolism. The serum estradiol target is similar to the mean daily level of premenopausal women (< 200 pg/mL) and the level of testosterone should be in the normal female range (< 55 ng/dL).^13,26-28

The selection of medications should be individualized for each patient. Comorbidities must be considered, as well as the risk for adverse effects, which include venous thromboembolism, elevated liver enzymes, breast cancer, cardiovascular disease, diabetes, hyperprolactinemia, weight gain, gallstones, cerebrovascular disease, and severe migraine headaches.^10,11 Estrogen therapy is not reported to induce hypertrophy or premalignant changes in the prostate.³³ As is the case for masculinizing hormones, feminizing hormone therapy should be continued indefinitely for long-term effects.

Frequent monitoring is recommended. Patients taking feminizing hormones (transwomen) should be seen every two to three months in the first year and monitored once or twice a year thereafter. Serum testosterone and estradiol levels should initially be monitored every three months; serum electrolytes, specifically potassium, should be monitored every two to three months in the first year until stable.

CASE 2 You recommend that Carol S be screened annually for sexually transmitted diseases, as you would for any 21-year-old patient. You point out, too, that while estrogen and androgen-suppressing therapy decrease sperm production, there is a possibility that the patient could impregnate a female partner and recommend that contraception be used if the couple is not trying to conceive.

You also discuss the risks and benefits of hormone therapy and reasonable expectations of continued treatment. You ask Carol to schedule a follow-up visit in six months, as her hormone regimen is stable. Finally, if the patient remains on hormone therapy, you mention that the only screening unique to men transitioning to women is for breast cancer, which should begin at age 40 to 50 (as it should for all women).

Gender-affirming surgical options

Surgical management of transgender patients is not within the scope of family medicine. But it is essential to know what procedures are available, as you may have occasion to advocate for patients during the surgical referral process and possibly to provide postoperative care.

For transmen, surgical options include chest reconstruction, hysterectomy/oophorectomy, metoidioplasty (using the clitoris to surgically approximate a penis), phalloplasty, scrotoplasty, urethroplasty, and vaginectomy.^10,34 The surgeries available for transwomen are orchiectomy, vaginoplasty, penectomy, breast augmentation, thyroid chondroplasty and voice surgery, and facial feminization.^10,34 Keep in mind that not all transgender individuals desire surgery as part of the transitioning process.
 

The authors would like to acknowledge the assistance of Michelle Forcier, MD, MPH, and Karen S. Bernstein, MD, MPH, in the preparation of this manuscript.

Civil rights for the lesbian, gay, bisexual, and transgender population have advanced markedly in the past decade, and the medical community has gradually begun to address more of their health concerns. More recently, media attention to transgender individuals has encouraged many more to openly seek care.^1,2

It is estimated that anywhere from 0.3% to 5% of the US population identifies as transgender.^1-3 While awareness of this population has slowly increased, there is a paucity of research on the hormone treatment that is often essential to patients’ well-being. Studies of surgical options for transgender patients have been minimal, as well.

Primary care providers are uniquely positioned to coordinate medical services and ensure continuity of care for transgender patients as they strive to become their authentic selves. Our goal in writing this article is to equip you with the tools to provide this patient population with sensitive, high-quality care (see Table 1).^4-7 Our focus is on the diagnosis of gender dysphoria (GD) and its medical and hormonal management—the realm of primary care providers. We briefly discuss surgical management of GD, as well.

UNDERSTANDING AND DIAGNOSING GENDER DYSPHORIA

Two classification systems are used for diagnoses related to GD: the Diagnostic and Statistical Manual of Mental Disorders, Fifth Ed (DSM-5)⁸ and the International Classification of Diseases, 10th Rev (ICD-10).⁹

ICD-10 criteria use the term gender identity disorder; DSM-5 refers to gender dysphoria instead. It is important to emphasize that these classification systems represent an attempt to categorize a group of signs and symptoms that lead to distress for the patient and are not meant to suggest that being transgender is pathological. In fact, in DSM-5—released in 2013—the American Psychiatric Association revised the terminology to emphasize that such individuals are not “disordered” by the nature of their identity, but rather by the distress that being transgender causes.⁸

For a diagnosis of GD in children, DSM-5 criteria include characteristics perceived to be incongruent between the child’s sex at birth and the self-identified gender based on preferred activities or dislike of his or her own sexual anatomy. The child must meet six or more of the following for at least six months

• A repeatedly stated desire to be, or insistence that he or she is, of the other gender
• In boys, a preference for cross-dressing or simulating female attire; in girls, insistence on wearing only stereotypical masculine clothing
• Strong and persistent preferences for cross-gender roles in make-believe play or fantasy
• A strong rejection of toys/games typically associated with the child’s sex
• Intense desire to participate in stereotypical games and pastimes of the other gender
• Strong preference for playmates of the other gender
• A strong dislike of one’s sexual anatomy
• A strong desire for the primary (eg, penis or vagina) or secondary (eg, menstruation) sex characteristics of the other gender.⁸

Adolescents and adults must meet two or more of the following for at least six months

• A noticeable incongruence between the gender that the patient sees themselves as and their sex characteristics
• An intense need to do away with (or prevent) his or her primary or secondary sex features
• An intense desire to have the primary and/or secondary sex features of the other gender
• A deep desire to transform into another gender
• A profound need for society to treat them as someone of the other gender
• A powerful assurance of having the characteristic feelings and responses of the other gender.⁸

For children as well as adolescents and adults, the condition should cause the patient significant distress or significantly affect him or her socially, at work or school, and in other important areas of life.⁸

Is the patient a candidate for hormone therapy?

Two primary sources—Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7, issued by the World Professional Association for Transgender Health (WPATH)¹⁰ and Endocrine Treatment of Transsexual Persons¹¹ by the Endocrine Society—offer clinical practice guidance based on evidence and expert opinion.

WPATH recommends that a mental health professional (MHP) experienced in transgender care diagnose GD to ensure that it is not mistaken for a psychiatric condition manifesting as altered gender identity. However, if no one with such experience is available or accessible in the region, it is reasonable for a primary care provider to make the diagnosis and consider initiating hormone therapy without a mental health referral,¹² as the expected benefits outweigh the risks of nontreatment.¹³

Whether or not an MHP confirms a diagnosis of GD, it is still up to the treating provider to confirm the patient’s eligibility and readiness for hormone therapy: He or she should meet DSM-5 or ICD-10 criteria for GD, have no psychiatric comorbidity (eg, schizophrenia, body dysmorphic disorder, or uncontrolled bipolar disorder) likely to interfere with treatment, understand the expected outcomes and the social benefits and risks, and have indicated a willingness to take the hormones responsibly.

Historically, patients were required to have a documented real-life experience, defined as having fully adopted the new gender role in everyday life for at least three months.^10,11 This model has fallen out of favor, however, as it is unsupported by evidence and may place transgender individuals at physical and emotional risk. Instead, readiness is confirmed by obtaining informed consent.¹²

Puberty may be suppressed with a gonadotropin-releasing hormone (GnRH) agonist in adolescents who have a GD diagnosis and are at Tanner stage 2 to 3 of puberty until age 16. At that point, hormone therapy consistent with their gender identification may be initiated (see “How to Help Transgender Teens”).¹¹

Beginning the transition

The transitioning process is a complex and individualized journey that can include inward or outward change, or both.

For patients interested in medical interventions, possible therapies include cross-sex hormone administration and gender-affirming surgery. Both are aimed at making the physical and the psychologic more congruent. Hormone treatment (see Table 2) is often essential to reduce the distress of individuals with GD and to help them feel comfortable in their own body.^10,11,21 Psychologic conditions, such as depression, tend to improve as the transitioning process gets underway.²²

FEMALE-TO-MALE TRANSITION

CASE 1 Jennie R, a 55-year-old postmenopausal patient, comes to your office for an annual exam. Although you’ve been her primary care provider for several years, she confides for the first time that she has never been comfortable as a woman. “I’ve always felt that my body didn’t belong to me,” the patient admits, and goes on to say that for the past several years she has been living as a man. Jennie R says she is ready to start hormone therapy to assist with the gender transition and asks about the process, the benefits and risks, and how quickly she can expect to achieve the desired results.

If Jennie R were your patient, how would you respond?

Masculinizing hormone treatment

As you would explain to a patient like Jennie R, the goal of hormone therapy is to suppress the effects of the sex assigned at birth and replace them with those of the desired gender. In the case of a female transitioning to a male (known as a transman), masculinizing hormones would promote growth of facial and body hair, cessation of menses, increased muscle mass, deepening of the voice, and clitoral enlargement.^11,23,24

Physical changes induced by masculinizing hormone therapy have an expected onset of one to six months and achieve maximum effect in approximately two to five years.^10,11 Although there have been no controlled clinical trials evaluating the safety or efficacy of any transitional hormone regimen, WPATH and the Center of Excellence for Transgender Health at the University of California, San Francisco, suggest initiating intramuscular or transdermal testosterone at increasing doses until normal physiologic male testosterone levels between 350 and 700 ng/dL are achieved, or until cessation of menses.^13,25-28 The dose at which either, or both, occur should be continued as long-term maintenance therapy. Medroxyprogesterone can be added, if necessary for menstrual cessation, and a GnRH agonist or endometrial ablation can be used for refractory uterine bleeding.^29,30

Testosterone is not a contraceptive. It is important to emphasize to transmen like Jennie that they remain at risk for pregnancy if they are having sex with fertile males. Caution patients not to assume that the possibility of pregnancy ends when menses stop.

Treat minor adverse effects. Adverse effects of masculinizing hormones include vaginal atrophy, fat redistribution and weight gain, polycythemia, acne, scalp hair loss, sleep apnea, elevated liver enzymes, hyperlipidemia, cardiovascular disease, diabetes, and bone density loss. Increased risk for cancer of the female organs has not been proven.^10,11 It is reasonable to treat minor adverse effects after reviewing the risks/benefits of doing so, as discontinuing hormone therapy could be detrimental to the well-being of transitioning patients.¹¹

There are absolute contraindications to masculinizing hormone therapy, however, including pregnancy, unstable coronary artery disease, and untreated polycythemia with a hematocrit > 55%.¹⁰

Monitoring is essential. Patients receiving masculinizing hormone therapy should be monitored every three months during the first year and once or twice a year there­after, with a focused history (including mood symptoms), physical exam (including weight and blood pressure), and labs (including complete blood count, liver function, renal function, and lipids) at each visit.^11,23 Some clinicians also check estradiol levels until they fall below 50 pg/mL,^23,27 while others take the cessation of uterine bleeding for > 6 months as an indicator of estrogen ­suppression.

Preventive health measures continue. Routine screening should continue, based on the patient’s assigned sex at birth. Thus, a transman who has not had a hysterectomy still needs Pap smears, mammograms if the patient has not had a double mastectomy, and bone mineral density (BMD) testing to screen for osteoporosis.^31,32 Some experts recommend starting to test BMD at age 50 for patients receiving masculinizing hormones, given the unknown effect of testosterone on bone density.^11,31,32

CASE 1 The first question for a transgender patient is about his or her current gender identity, but Jennie R has already reported living as a man. So you start by asking “What name do you prefer to use?” and “Do you prefer to be referred to with male or female pronouns?”

The patient tells you that he sees himself as a man, he wants to be called Jeff, and he prefers male pronouns. You explain that you believe he has gender dysphoria and would benefit from hormone therapy, but it is important to confirm this diagnosis with an MHP. You explain that testosterone can be prescribed for masculinizing effects, and describe the expected effects—more facial and body hair, a deeper voice, and greater muscle mass, among others—and review the likely time frame.

You also discuss the risks of masculinizing hormones (hyperlipidemia, cardiovascular disease, diabetes, and loss of bone density) that will need to be monitored. Before he leaves, you give him the name of an MHP who is experienced in transgender care and tell him to make a follow-up appointment with you after he has seen her. At the conclusion of the visit, you make a note of the patient’s name and gender identity in the chart and inform the staff of the changes.

MALE-TO-FEMALE TRANSITION

CASE 2 Before heading into your office to talk to a new patient named Carl S, you glance at his chart and see that he is a healthy 21-year-old who has come in for a routine physical. When you enter the room, you find Carl wearing a dress, heels, and make-up. After confirming that you have the right patient, you ask, “What is your current gender identity?” “Female,” says Carl, who indicates that she now goes by Carol. The patient has no medical problems, surgical history, or significant family history but reports that she has been taking spironolactone and estrogen for the past three years. Carol also says she has a new female partner and is having unprotected sexual activity.

Feminizing hormone treatment

The desired effects of feminizing hormones include voice change, decreased hair growth, breast growth, body fat redistribution, decreased muscle mass, skin softening, decreased oiliness of skin and hair, and a decrease in spontaneous erections, testicular volume, and sperm production.^10,11 The onset of feminizing effects ranges from one month to one year and the expected maximum effect occurs anywhere between three months and five years.^10,11 Regimens usually include anti-androgen agents and estrogen.^13,26-28

The medications that have been most studied with anti-androgenic effects include spironolactone and 5-α reductase inhibitors (5-ARIs) such as finasteride. Spironolactone inhibits testosterone secretion and inhibits androgen binding to androgen receptors; 5-ARIs block the conversion of testosterone to 5-α-dihydrotestosterone, the more active form.

Estrogen can be administered via oral, sublingual, transdermal, or intramuscular route, but parenteral formulations are preferred to avoid first-pass metabolism. The serum estradiol target is similar to the mean daily level of premenopausal women (< 200 pg/mL) and the level of testosterone should be in the normal female range (< 55 ng/dL).^13,26-28

The selection of medications should be individualized for each patient. Comorbidities must be considered, as well as the risk for adverse effects, which include venous thromboembolism, elevated liver enzymes, breast cancer, cardiovascular disease, diabetes, hyperprolactinemia, weight gain, gallstones, cerebrovascular disease, and severe migraine headaches.^10,11 Estrogen therapy is not reported to induce hypertrophy or premalignant changes in the prostate.³³ As is the case for masculinizing hormones, feminizing hormone therapy should be continued indefinitely for long-term effects.

Frequent monitoring is recommended. Patients taking feminizing hormones (transwomen) should be seen every two to three months in the first year and monitored once or twice a year thereafter. Serum testosterone and estradiol levels should initially be monitored every three months; serum electrolytes, specifically potassium, should be monitored every two to three months in the first year until stable.

CASE 2 You recommend that Carol S be screened annually for sexually transmitted diseases, as you would for any 21-year-old patient. You point out, too, that while estrogen and androgen-suppressing therapy decrease sperm production, there is a possibility that the patient could impregnate a female partner and recommend that contraception be used if the couple is not trying to conceive.

You also discuss the risks and benefits of hormone therapy and reasonable expectations of continued treatment. You ask Carol to schedule a follow-up visit in six months, as her hormone regimen is stable. Finally, if the patient remains on hormone therapy, you mention that the only screening unique to men transitioning to women is for breast cancer, which should begin at age 40 to 50 (as it should for all women).

Gender-affirming surgical options

Surgical management of transgender patients is not within the scope of family medicine. But it is essential to know what procedures are available, as you may have occasion to advocate for patients during the surgical referral process and possibly to provide postoperative care.

For transmen, surgical options include chest reconstruction, hysterectomy/oophorectomy, metoidioplasty (using the clitoris to surgically approximate a penis), phalloplasty, scrotoplasty, urethroplasty, and vaginectomy.^10,34 The surgeries available for transwomen are orchiectomy, vaginoplasty, penectomy, breast augmentation, thyroid chondroplasty and voice surgery, and facial feminization.^10,34 Keep in mind that not all transgender individuals desire surgery as part of the transitioning process.
 

The authors would like to acknowledge the assistance of Michelle Forcier, MD, MPH, and Karen S. Bernstein, MD, MPH, in the preparation of this manuscript.

The 2016 hospital-acquired and ventilator-associated pneumonia guidelines, sponsored by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS), and endorsed by the American College of Chest Physicians (CHEST), Society of Critical Care Medicine (SCCM), and the Society for Healthcare Epidemiology, was published recently (Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63[5]:575-82).

This Critical Care Commentary aims to provide the highlights of the new guideline and to motivate readers to read the complete report that best represents the primary intent of the guideline panelists.

Dr. Kalil is with the department of internal medicine, division of infectious diseases, University of Nebraska Medical Center, Omaha; Dr. Metersky is with the division of pulmonary and critical care medicine, University of Connecticut, Farmington.

The 2016 hospital-acquired and ventilator-associated pneumonia guidelines, sponsored by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS), and endorsed by the American College of Chest Physicians (CHEST), Society of Critical Care Medicine (SCCM), and the Society for Healthcare Epidemiology, was published recently (Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63[5]:575-82).

This Critical Care Commentary aims to provide the highlights of the new guideline and to motivate readers to read the complete report that best represents the primary intent of the guideline panelists.

Dr. Kalil is with the department of internal medicine, division of infectious diseases, University of Nebraska Medical Center, Omaha; Dr. Metersky is with the division of pulmonary and critical care medicine, University of Connecticut, Farmington.

The 2016 hospital-acquired and ventilator-associated pneumonia guidelines, sponsored by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS), and endorsed by the American College of Chest Physicians (CHEST), Society of Critical Care Medicine (SCCM), and the Society for Healthcare Epidemiology, was published recently (Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63[5]:575-82).

This Critical Care Commentary aims to provide the highlights of the new guideline and to motivate readers to read the complete report that best represents the primary intent of the guideline panelists.

Dr. Kalil is with the department of internal medicine, division of infectious diseases, University of Nebraska Medical Center, Omaha; Dr. Metersky is with the division of pulmonary and critical care medicine, University of Connecticut, Farmington.

Appropriate use of adjuvant endocrine therapy for breast cancer improved over a 10-year period, but optimal use has not been achieved, according to findings from a retrospective review of more than 980,000 women with stages I-III breast cancer.

As a result, an estimated 14,630 lives were unnecessarily lost during the study period, according to Bobby M. Daly, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.

Of the 981,729 women in the National Cancer Database from Jan. 1, 2004, to Dec. 31, 2013, who received all or part of their care at the reporting institution and who met eligibility criteria, 818,435 had hormone receptor positive (HR+) disease and 163,294 had hormone receptor negative (HR-) disease.

The percentage of HR+ patients receiving adjuvant endocrine therapy (AET) increased from 69.8% in 2004 to 82.4% in 2013 (annual percentage change, 1.51%), and the percentage of HR- patients decreased from 5.2% to 3.4% during the same time period (annual percentage change, -0.17%), the authors reported online Feb. 2 in JAMA Oncology (2017 Feb 2. doi: 10.1001jamaoncol.2016.6380).

MACRA may boost outcomes

In an interview, Dr. Daly said he believes the coming changes with respect to value-based reimbursement will indeed have an important impact on outcomes.

“The oncology care model, for example, mandates that physicians document that they are providing guideline-concordant care,” said Dr. Daly, assistant attending physician at Memorial Sloan Kettering Cancer Center. “There are also new technologies such as oncology clinical pathways ... that also try to ensure that all patients are receiving care according to guidelines.”

Further, the increasing use of team-based approaches to care and the incorporation of “tumor boards” might explain the growth in optimal AET usage seen in this cohort.

Dr. Daly said he was surprised to find that certain patient groups were being left behind, such as those with estrogen receptor-negative/progesterone receptor-positive disease, African American patients, and younger and older patients, who were less likely to receive AET.

“I think that helps us also focus on patient populations we can target to make sure they are receiving optimal care,” he said, stressing that the findings have important policy implications for figuring out why those patients are being left behind, and raising the standard of care for all patients.

“We are making great strides to providing appropriate guideline-concordant care for breast cancer patients, but there’s still room to improve,” he said.

Dr. Daly serves as a director of and receives compensation from Quadrant Holdings. Frontline Medical News is a subsidiary of Quadrant Holdings. Dr. Daly also reported financial relationships with CVS Health, Johnson & Johnson, McKesson, and Walgreens Boots Alliance.

[email protected]

Appropriate use of adjuvant endocrine therapy for breast cancer improved over a 10-year period, but optimal use has not been achieved, according to findings from a retrospective review of more than 980,000 women with stages I-III breast cancer.

As a result, an estimated 14,630 lives were unnecessarily lost during the study period, according to Bobby M. Daly, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.

Of the 981,729 women in the National Cancer Database from Jan. 1, 2004, to Dec. 31, 2013, who received all or part of their care at the reporting institution and who met eligibility criteria, 818,435 had hormone receptor positive (HR+) disease and 163,294 had hormone receptor negative (HR-) disease.

The percentage of HR+ patients receiving adjuvant endocrine therapy (AET) increased from 69.8% in 2004 to 82.4% in 2013 (annual percentage change, 1.51%), and the percentage of HR- patients decreased from 5.2% to 3.4% during the same time period (annual percentage change, -0.17%), the authors reported online Feb. 2 in JAMA Oncology (2017 Feb 2. doi: 10.1001jamaoncol.2016.6380).

MACRA may boost outcomes

In an interview, Dr. Daly said he believes the coming changes with respect to value-based reimbursement will indeed have an important impact on outcomes.

“The oncology care model, for example, mandates that physicians document that they are providing guideline-concordant care,” said Dr. Daly, assistant attending physician at Memorial Sloan Kettering Cancer Center. “There are also new technologies such as oncology clinical pathways ... that also try to ensure that all patients are receiving care according to guidelines.”

Further, the increasing use of team-based approaches to care and the incorporation of “tumor boards” might explain the growth in optimal AET usage seen in this cohort.

Dr. Daly said he was surprised to find that certain patient groups were being left behind, such as those with estrogen receptor-negative/progesterone receptor-positive disease, African American patients, and younger and older patients, who were less likely to receive AET.

“I think that helps us also focus on patient populations we can target to make sure they are receiving optimal care,” he said, stressing that the findings have important policy implications for figuring out why those patients are being left behind, and raising the standard of care for all patients.

“We are making great strides to providing appropriate guideline-concordant care for breast cancer patients, but there’s still room to improve,” he said.

Dr. Daly serves as a director of and receives compensation from Quadrant Holdings. Frontline Medical News is a subsidiary of Quadrant Holdings. Dr. Daly also reported financial relationships with CVS Health, Johnson & Johnson, McKesson, and Walgreens Boots Alliance.

[email protected]

Appropriate use of adjuvant endocrine therapy for breast cancer improved over a 10-year period, but optimal use has not been achieved, according to findings from a retrospective review of more than 980,000 women with stages I-III breast cancer.

As a result, an estimated 14,630 lives were unnecessarily lost during the study period, according to Bobby M. Daly, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.

Of the 981,729 women in the National Cancer Database from Jan. 1, 2004, to Dec. 31, 2013, who received all or part of their care at the reporting institution and who met eligibility criteria, 818,435 had hormone receptor positive (HR+) disease and 163,294 had hormone receptor negative (HR-) disease.

The percentage of HR+ patients receiving adjuvant endocrine therapy (AET) increased from 69.8% in 2004 to 82.4% in 2013 (annual percentage change, 1.51%), and the percentage of HR- patients decreased from 5.2% to 3.4% during the same time period (annual percentage change, -0.17%), the authors reported online Feb. 2 in JAMA Oncology (2017 Feb 2. doi: 10.1001jamaoncol.2016.6380).

MACRA may boost outcomes

In an interview, Dr. Daly said he believes the coming changes with respect to value-based reimbursement will indeed have an important impact on outcomes.

“The oncology care model, for example, mandates that physicians document that they are providing guideline-concordant care,” said Dr. Daly, assistant attending physician at Memorial Sloan Kettering Cancer Center. “There are also new technologies such as oncology clinical pathways ... that also try to ensure that all patients are receiving care according to guidelines.”

Further, the increasing use of team-based approaches to care and the incorporation of “tumor boards” might explain the growth in optimal AET usage seen in this cohort.

Dr. Daly said he was surprised to find that certain patient groups were being left behind, such as those with estrogen receptor-negative/progesterone receptor-positive disease, African American patients, and younger and older patients, who were less likely to receive AET.

“I think that helps us also focus on patient populations we can target to make sure they are receiving optimal care,” he said, stressing that the findings have important policy implications for figuring out why those patients are being left behind, and raising the standard of care for all patients.

“We are making great strides to providing appropriate guideline-concordant care for breast cancer patients, but there’s still room to improve,” he said.

Dr. Daly serves as a director of and receives compensation from Quadrant Holdings. Frontline Medical News is a subsidiary of Quadrant Holdings. Dr. Daly also reported financial relationships with CVS Health, Johnson & Johnson, McKesson, and Walgreens Boots Alliance.

[email protected]

AMSTERDAM – Five years after a cancer diagnosis, patients who report having chronic neuropathic pain are twice as likely to be out of work as patients who report having no neuropathic pain, authors of a large longitudinal study said.

“For middle-term cancer survivors, suffering from chronic neuropathic pain unfortunately predicts labor-market exit,” said Marc-Karim Bendiane, from Aix-Marseille University in Marseille, France.

Pain is still frequently underdiagnosed, poorly managed, and undertreated among cancer survivors, and there is a need for alternatives to analgesics for control of chronic neuropathic pain (CNP), Mr. Bendiane said at an annual congress sponsored by the European Cancer Organisation.

Mr. Bendiane and colleagues used data from VICAN, a longitudinal survey of issues of concern to cancer survivors 2 years and 5 years after a diagnosis. The cohort consists of patients diagnosed with cancers who comprise 88% of all cancer diagnoses in France, including cancers of the breast; colon and rectum; lip, oral cavity, and pharynx; kidney; cervix; endometrium; non-Hodgkin lymphoma; melanoma; thyroid; bladder; and prostate.

[email protected]

AMSTERDAM – Five years after a cancer diagnosis, patients who report having chronic neuropathic pain are twice as likely to be out of work as patients who report having no neuropathic pain, authors of a large longitudinal study said.

“For middle-term cancer survivors, suffering from chronic neuropathic pain unfortunately predicts labor-market exit,” said Marc-Karim Bendiane, from Aix-Marseille University in Marseille, France.

Pain is still frequently underdiagnosed, poorly managed, and undertreated among cancer survivors, and there is a need for alternatives to analgesics for control of chronic neuropathic pain (CNP), Mr. Bendiane said at an annual congress sponsored by the European Cancer Organisation.

Mr. Bendiane and colleagues used data from VICAN, a longitudinal survey of issues of concern to cancer survivors 2 years and 5 years after a diagnosis. The cohort consists of patients diagnosed with cancers who comprise 88% of all cancer diagnoses in France, including cancers of the breast; colon and rectum; lip, oral cavity, and pharynx; kidney; cervix; endometrium; non-Hodgkin lymphoma; melanoma; thyroid; bladder; and prostate.

[email protected]

AMSTERDAM – Five years after a cancer diagnosis, patients who report having chronic neuropathic pain are twice as likely to be out of work as patients who report having no neuropathic pain, authors of a large longitudinal study said.

“For middle-term cancer survivors, suffering from chronic neuropathic pain unfortunately predicts labor-market exit,” said Marc-Karim Bendiane, from Aix-Marseille University in Marseille, France.

Pain is still frequently underdiagnosed, poorly managed, and undertreated among cancer survivors, and there is a need for alternatives to analgesics for control of chronic neuropathic pain (CNP), Mr. Bendiane said at an annual congress sponsored by the European Cancer Organisation.

Mr. Bendiane and colleagues used data from VICAN, a longitudinal survey of issues of concern to cancer survivors 2 years and 5 years after a diagnosis. The cohort consists of patients diagnosed with cancers who comprise 88% of all cancer diagnoses in France, including cancers of the breast; colon and rectum; lip, oral cavity, and pharynx; kidney; cervix; endometrium; non-Hodgkin lymphoma; melanoma; thyroid; bladder; and prostate.

[email protected]

LAS VEGAS – Children born to obese women with insulin resistance during pregnancy showed significantly impaired neurodevelopment at 2 years of age, compared with children born to obese mothers without insulin resistance in a prospective observational study with 75 pregnant women.

The neurodevelopmental deficits were specific for the domains of motor function and attention, and the deficits correlated with several markers of abnormal glucose and fat metabolism in the insulin-resistant women, Alison G. Cahill, MD, said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“The differences in neurodevelopment appear to not be global but instead specifically affect domains of motor development and attention,” said Dr. Cahill, chief of maternal fetal medicine at Washington University in St. Louis. “These findings are consistent with results from animal studies that suggest certain brain regions are more sensitive than others to metabolic abnormalities” while in utero.

“These are among the first data in humans to characterize the impact of metabolic abnormalities on brain development,” she added.

Mitchel L. Zoler/Frontline Medical News

[email protected] On Twitter @mitchelzoler

LAS VEGAS – Children born to obese women with insulin resistance during pregnancy showed significantly impaired neurodevelopment at 2 years of age, compared with children born to obese mothers without insulin resistance in a prospective observational study with 75 pregnant women.

The neurodevelopmental deficits were specific for the domains of motor function and attention, and the deficits correlated with several markers of abnormal glucose and fat metabolism in the insulin-resistant women, Alison G. Cahill, MD, said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“The differences in neurodevelopment appear to not be global but instead specifically affect domains of motor development and attention,” said Dr. Cahill, chief of maternal fetal medicine at Washington University in St. Louis. “These findings are consistent with results from animal studies that suggest certain brain regions are more sensitive than others to metabolic abnormalities” while in utero.

“These are among the first data in humans to characterize the impact of metabolic abnormalities on brain development,” she added.

Mitchel L. Zoler/Frontline Medical News

[email protected] On Twitter @mitchelzoler

LAS VEGAS – Children born to obese women with insulin resistance during pregnancy showed significantly impaired neurodevelopment at 2 years of age, compared with children born to obese mothers without insulin resistance in a prospective observational study with 75 pregnant women.

The neurodevelopmental deficits were specific for the domains of motor function and attention, and the deficits correlated with several markers of abnormal glucose and fat metabolism in the insulin-resistant women, Alison G. Cahill, MD, said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“The differences in neurodevelopment appear to not be global but instead specifically affect domains of motor development and attention,” said Dr. Cahill, chief of maternal fetal medicine at Washington University in St. Louis. “These findings are consistent with results from animal studies that suggest certain brain regions are more sensitive than others to metabolic abnormalities” while in utero.

“These are among the first data in humans to characterize the impact of metabolic abnormalities on brain development,” she added.

Mitchel L. Zoler/Frontline Medical News

[email protected] On Twitter @mitchelzoler