Conference Coverage

Ovarian reserve markers fall on isotretinoin, but rebound after stopping treatment



Female patients who used systemic isotretinoin for acne saw a drop in markers for ovarian reserve, but the effect was reversed when treatment was stopped, according to data presented at the World Congress of Dermatology.

Wikimedia Commons/Kinan Ayu/Creative Commons

Although markers for ovarian reserve, including anti-Müllerian hormone (AMH) serum levels, ovarian volume, and antral follicle count, were significantly lower during a period of isotretinoin use than at baseline, these values were were not significantly different from pretreatment levels by 1 month after stopping isotretinoin.

For patients taking isotretinoin at a dose of 0.5 mg/kg/day, AMH levels fell from a baseline level of 5.29 ng/mL to 4.16 ng/mL during treatment, but rebounded to 4.77 ng/mL 1 month after stopping treatment (P less than .001 for difference between baseline and on-drug values), Tuğba Özkök Akbulut, MD, said during a late-breaking abstracts session.

For women taking isotretinoin 1 mg/kg/day, AMH levels went from 5.14 ng/mL at baseline to 4.24 ng/mL on treatment, to 4.65 ng/mL 1 month after treatment (P less than .001 for difference between baseline and on-drug values), reported Dr. Akbulut a dermatologist at the Haseki Training Research Hospital, Istanbul.

Women on the higher dose of isotretinoin had a similar pattern of decline while on treatment and rebound after ceasing isotretinoin for ovarian volume and antral follicle count (P less than .001 for all values). These differences were not statistically significant for women taking 0.5 mg/kg/day of isotretinoin, except for right ovarian volume (P = 0.013).

Although values were numerically lower for many markers of ovarian reserve after ceasing treatment, compared with baseline figures, these differences were not statistically significantly different. Markers of ovarian reserve did not change significantly for a control group of women without acne.

Dr. Akbulut and her colleagues conducted this prospective case-control study of 42 women of reproductive age who sought dermatologist care for severe acne unresponsive to conservative therapy; 26 women who did not have acne constituted the control group. Smokers, patients with thyroid disease, and those with known polycystic ovary syndrome were excluded from participation.

The women with acne received oral isotretinoin dosed either at 0.5 or 1.0 mg/kg/day, with treatment lasting 5-9 months. For each patient, treatment was stopped when the cumulative dose reached 120 mg/kg.

After an initial visit at which blood was collected from all participants to measure serum AMH levels, those receiving isotretinoin were seen every 4 weeks to check serum lipid and liver enzyme levels.

At the 3-month mark during the study period and 1 month after the end of completing isotretinoin treatment, or at the end of the study period for the control group, blood samples also were drawn for AMH levels.

To measure hormone levels, also blood was drawn between days 2 and 5 of the follicular phase of the menstrual cycle. Participants received ultrasounds to measure antral follicle count and ovarian volume between days 2 and 5 of the menstrual cycle at the initial visit, at the 3-month visit, and at the final visit. Results were interpreted by a trained gynecologist.

Patients, who were mostly in their early 20s, had a mean body mass index of about 22 kg/m2. Hormone levels, ovarian volume, and antral follicle count did not differ among study arms at baseline.

“There are contradictory reports in the literature regarding the effect of retinoic acid on ovarian reserve,” noted Dr. Akbulut. Some preclinical studies found that retinoic acid increased fertility and ovarian reserve in rodents; however, some human studies had shown lower serum AMH concentrations in patients using isotretinoin.

This new demonstration of the reversibility of isotretinoin’s negative effect on ovarian reserve helps clarify a confused picture in the medical literature, said Dr. Akbulut. “The results of our study demonstrated that systemic isotretinoin had a reversible effect on ovarian reserve.”

Dr. Akbulut reported no outside sources of funding and that she had no relevant financial disclosures.

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