In PCOS, 10 Days of Clomiphene Better Than 5

ORLANDO – A simple regimen change – giving half the dose of clomiphene over twice as many days – significantly improved ovulation and pregnancy rates in a study of women with polycystic ovary syndrome and clomiphene-resistant anovulation.

The study involved 220 women who failed to respond to an initial regimen of clomiphene citrate. Dr. Mervat Omran compared outcomes between 110 women randomized to 200 mg clomiphene (four 50-mg tablets daily) for 5 days and 100 women randomized to 100 mg/day (two tablets) for 10 days.

The extended duration protocol resulted in a significantly higher ovulation rate, a higher number of dominant follicles, better endometrium at ovulation, and a higher pregnancy rate than the 5-day protocol, despite an equal total dose of clomiphene per cycle, Dr. Omran said at the meeting.

About 20%-25% of polycystic ovary syndrome (PCOS) patients have clomiphene-resistant anovulation, defined as a lack of ovulatory response after the standard dose of 100 mg/day for 5 days, Dr. Omran said.

One solution is to try to increase the amplitude or duration of treatment, said Dr. Omran, an ob.gyn. at the University of Alexandria (Egypt).

Women in the 10-day group had a significantly higher ovulation rate, 37%, compared with 10% in the 5-day group. Also, “the endometrium at ovulation was significantly thicker … and the clinical pregnancy rate was significantly higher in the longer duration group,” she said.

These regimens represent an off-label use in the United States. The Food and Drug Administration–recommended dosage is an initial 50 mg clomiphene per day for 5 days to stimulate ovulation. Unresponsive patients can be given 100 mg daily for 5 days, but increasing the dosage or duration of therapy beyond this dosage is not recommended.

“We should start by dosing no more than 100 mg clomiphene per day for 5 days,” Dr. Omran said, “but if the patient [does] not respond, I think it's better to prolong the duration than to increase the dose.”

It may be that longer exposure to clomiphene might increase stimulation of follicles in these patients to a greater degree than simply higher doses, Dr. Omran said.

“That's why I think your approach is interesting,” said session comoderator Dr. James Segars Jr. “You're saying, basically, maybe it takes a little longer duration to get physiologic effect, and you clearly showed there is a big difference.”

“We typically give Clomid 50s for 5 days. Maybe the next logical step is to look at 50 mg for 10 days” and then try 100 mg for 10 days if response remains suboptimal, said Dr. Segars of the National Institute of Child Health and Human Development in Bethesda, Md.

Measurement of serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) on day 6 and day 10 were strengths of the study, Dr. Omran said. Day 6 FSH levels did not differ significantly between 6.9 mIU/mL in the 5-day group and 6.2 mIU/mL in the 10-day group. Therefore, the higher dose clomiphene regimen did not significantly increase the amplitude of FSH at day 6, she added.

“However, day 10 FSH was significantly higher in the group that used the longer regimen [6.3 mIU/mL versus 3.8 mIU/mL], indicating that prolonging the duration of treatment might be better than increasing the dose of clomiphene,” Dr. Omran said.

ORLANDO – A simple regimen change – giving half the dose of clomiphene over twice as many days – significantly improved ovulation and pregnancy rates in a study of women with polycystic ovary syndrome and clomiphene-resistant anovulation.

The study involved 220 women who failed to respond to an initial regimen of clomiphene citrate. Dr. Mervat Omran compared outcomes between 110 women randomized to 200 mg clomiphene (four 50-mg tablets daily) for 5 days and 100 women randomized to 100 mg/day (two tablets) for 10 days.

The extended duration protocol resulted in a significantly higher ovulation rate, a higher number of dominant follicles, better endometrium at ovulation, and a higher pregnancy rate than the 5-day protocol, despite an equal total dose of clomiphene per cycle, Dr. Omran said at the meeting.

About 20%-25% of polycystic ovary syndrome (PCOS) patients have clomiphene-resistant anovulation, defined as a lack of ovulatory response after the standard dose of 100 mg/day for 5 days, Dr. Omran said.

One solution is to try to increase the amplitude or duration of treatment, said Dr. Omran, an ob.gyn. at the University of Alexandria (Egypt).

Women in the 10-day group had a significantly higher ovulation rate, 37%, compared with 10% in the 5-day group. Also, “the endometrium at ovulation was significantly thicker … and the clinical pregnancy rate was significantly higher in the longer duration group,” she said.

These regimens represent an off-label use in the United States. The Food and Drug Administration–recommended dosage is an initial 50 mg clomiphene per day for 5 days to stimulate ovulation. Unresponsive patients can be given 100 mg daily for 5 days, but increasing the dosage or duration of therapy beyond this dosage is not recommended.

“We should start by dosing no more than 100 mg clomiphene per day for 5 days,” Dr. Omran said, “but if the patient [does] not respond, I think it's better to prolong the duration than to increase the dose.”

It may be that longer exposure to clomiphene might increase stimulation of follicles in these patients to a greater degree than simply higher doses, Dr. Omran said.

“That's why I think your approach is interesting,” said session comoderator Dr. James Segars Jr. “You're saying, basically, maybe it takes a little longer duration to get physiologic effect, and you clearly showed there is a big difference.”

“We typically give Clomid 50s for 5 days. Maybe the next logical step is to look at 50 mg for 10 days” and then try 100 mg for 10 days if response remains suboptimal, said Dr. Segars of the National Institute of Child Health and Human Development in Bethesda, Md.

Measurement of serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) on day 6 and day 10 were strengths of the study, Dr. Omran said. Day 6 FSH levels did not differ significantly between 6.9 mIU/mL in the 5-day group and 6.2 mIU/mL in the 10-day group. Therefore, the higher dose clomiphene regimen did not significantly increase the amplitude of FSH at day 6, she added.

“However, day 10 FSH was significantly higher in the group that used the longer regimen [6.3 mIU/mL versus 3.8 mIU/mL], indicating that prolonging the duration of treatment might be better than increasing the dose of clomiphene,” Dr. Omran said.

ORLANDO – A simple regimen change – giving half the dose of clomiphene over twice as many days – significantly improved ovulation and pregnancy rates in a study of women with polycystic ovary syndrome and clomiphene-resistant anovulation.

The study involved 220 women who failed to respond to an initial regimen of clomiphene citrate. Dr. Mervat Omran compared outcomes between 110 women randomized to 200 mg clomiphene (four 50-mg tablets daily) for 5 days and 100 women randomized to 100 mg/day (two tablets) for 10 days.

The extended duration protocol resulted in a significantly higher ovulation rate, a higher number of dominant follicles, better endometrium at ovulation, and a higher pregnancy rate than the 5-day protocol, despite an equal total dose of clomiphene per cycle, Dr. Omran said at the meeting.

About 20%-25% of polycystic ovary syndrome (PCOS) patients have clomiphene-resistant anovulation, defined as a lack of ovulatory response after the standard dose of 100 mg/day for 5 days, Dr. Omran said.

One solution is to try to increase the amplitude or duration of treatment, said Dr. Omran, an ob.gyn. at the University of Alexandria (Egypt).

Women in the 10-day group had a significantly higher ovulation rate, 37%, compared with 10% in the 5-day group. Also, “the endometrium at ovulation was significantly thicker … and the clinical pregnancy rate was significantly higher in the longer duration group,” she said.

These regimens represent an off-label use in the United States. The Food and Drug Administration–recommended dosage is an initial 50 mg clomiphene per day for 5 days to stimulate ovulation. Unresponsive patients can be given 100 mg daily for 5 days, but increasing the dosage or duration of therapy beyond this dosage is not recommended.

“We should start by dosing no more than 100 mg clomiphene per day for 5 days,” Dr. Omran said, “but if the patient [does] not respond, I think it's better to prolong the duration than to increase the dose.”

It may be that longer exposure to clomiphene might increase stimulation of follicles in these patients to a greater degree than simply higher doses, Dr. Omran said.

“That's why I think your approach is interesting,” said session comoderator Dr. James Segars Jr. “You're saying, basically, maybe it takes a little longer duration to get physiologic effect, and you clearly showed there is a big difference.”

“We typically give Clomid 50s for 5 days. Maybe the next logical step is to look at 50 mg for 10 days” and then try 100 mg for 10 days if response remains suboptimal, said Dr. Segars of the National Institute of Child Health and Human Development in Bethesda, Md.

Measurement of serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) on day 6 and day 10 were strengths of the study, Dr. Omran said. Day 6 FSH levels did not differ significantly between 6.9 mIU/mL in the 5-day group and 6.2 mIU/mL in the 10-day group. Therefore, the higher dose clomiphene regimen did not significantly increase the amplitude of FSH at day 6, she added.

“However, day 10 FSH was significantly higher in the group that used the longer regimen [6.3 mIU/mL versus 3.8 mIU/mL], indicating that prolonging the duration of treatment might be better than increasing the dose of clomiphene,” Dr. Omran said.