Effects of subchronic infusion of dehydroepiandrosterone sulfate on serum gonadotropin levels and ovarian function in the cynomolgus monkey

Abstract

Objective: To assess the impact of elevated adrenal androgen levels on ovarian function in a nonhuman primate using a repeated measures experimental design.

Design: Osmotic pumps that released dehydroepiandrosterone sulfate (DHEAS) were implanted subcutaneously in five cynomolgus monkeys (Macaca fascicularis) for one menstrual cycle. The pumps were filled with saline for the two control cycles, one preceding and the other following DHEAS infusion.

Results: Administration of DHEAS elevated its levels in serum fourfold and in urine sevenfold, which returned to pretreatment values in the next cycle. Serum concentrations of estradiol (E2) were reduced by 55% during DHEAS administration in both follicular and luteal phases and were still decreased in the following cycle by 69% in follicular phase and 48% in luteal phase (P less than 0.01). Luteal serum progesterone (P) levels were diminished by 52% during treatment and were accompanied by 56% reduction in immunoreactive pregnanediol excretion in urine (P less than 0.05). Serum luteinizing hormone (LH) levels were decreased during DHEAS infusion by 51% in follicular phase and 58% in luteal phase (P less than 0.01) but returned to baseline in the next cycle. Conversely, serum follicle-stimulating hormone (FSH) concentrations were increased during treatment by 70% in follicular phase and 101% in luteal phase and remained increased by 58% in follicular phase of the next cycle (P less than 0.05). Estrone excretion in urine was higher during DHEAS infusion (1.5-fold increase) but was below pretreatment values in the following cycle by 57% in follicular phase and 51% in luteal phase (P less than 0.001). Administration of DHEAS did not change significantly serum levels of sex hormone-binding globulin. The length of menstrual cycles was not affected by increased levels of adrenal androgens either. However, in the cycles that followed DHEAS infusion, follicular phase was prolonged by an average of 9 days, and luteal phase was shortened by an average of 5 days (P less than 0.01).

Conclusions: These data document that subchronically elevated adrenal androgen levels in primates: (1) suppress E2 and P levels, which may affect fertility; (2) differentially affect gonadotropin secretion, decreasing LH and increasing FSH serum concentrations; and (3) result in disturbances of ovarian function that persist for at least one menstrual cycle after normalization of androgen levels.