Endocrine Abstracts

Background: Ketoconazole is a synthetic antifungal drug, and powerful inhibitor of steroidogenesis. Oral ketoconazole blocks both ovarian and adrenal androgen biosynthesis, and glucocorticoid synthesis, leading to a reduction in circulating testosterone and cortisol levels. In subjects with an intact HPA axis, ketoconazole by decreasing cortisol levels leads to compensatory rise an ACTH level.

Objectives: To assess influence ketoconasole induced changes in steroid synthesis on the hypothalamo-pituitary–gonadal axis and adrenal activity in PCOS.

Methods: The study group consisted of 44 women (i. PCOS group, n=21; ii. control group, n=23). During the follicular phase of menstrual cycle, 2×400 mg of oral ketoconazole was given. We measured FSH, LH, testosterone, DHEA-s, progesterone and 17-OH progesterone before ketoconazole and the morning after ketoconazole. Changes in the hormone concentrations were analyzed using Wilcoxon test, and presented as median (range) of the hormone change after ketoconazole. Positive values indicate increase and negative decrease after ketoconazole.

Results: FSH: 0.61±1.19 vs 0.84±1.86 IU/l; P=0.47; LH: 2.34±3.81 vs −0.11±2.4 IU/l; P=0.02; testosterone −1.19±0.83 vs −0.35±0.48 nmol/l; P<0.01; DHEA-s −1.28±1.19 vs −0.99±2.11 nmol/l; P=0.18; progesterone 15.86±15.10 vs 18.71±22.60; P=0.89; 17OH progesterone: 1.71±1.79 vs 0.95±1.07; P=0.15; testosterone was significantly more suppressed in PCOS compared to control group. There was significant increase in LH in PCOS compared to control group.

Conclusions: Androgen synthesis in PCOS is more sensitive to ketoconazole inhibition than in non-PCOS subjects. This implies that it has a potential role in the PCOS treatment.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.