Increased androgen, anti-Müllerian hormone, and sporadic anovulation in healthy, eumenorrheic women: a mild PCOS-like phenotype?

CONTEXT: Hyperandrogenism is a hallmark of polycystic ovary syndrome (PCOS) in women with irregular menses, yet the relationship between androgens and ovarian dysfunction remains poorly understood in eumenorrheic women.

OBJECTIVE

The objective of the study was to evaluate whether sporadic anovulation was associated with higher T and anti-müllerian hormone (AMH; marker of ovarian follicle count) concentrations in eumenorrheic women.

DESIGN

This was a prospective cohort study from 2005 to 2007.

SETTING

The study was conducted at the University of Buffalo in western New York state.

PARTICIPANTS

A total of 259 eumenorrheic women without a self-reported history of infertility, PCOS, or other endocrine disorder participated in the study.

MAIN OUTCOME MEASURES: Total T and AMH were measured five to eight times per cycle for one (n = 9) or two (n = 250) cycles per woman (n = 509 cycles) with timing of menstrual cycle phase assisted by fertility monitors. Anovulatory cycles were defined biochemically by progesterone and LH concentrations. Repeated-measures ANOVA was conducted on log-transformed data with adjustment for age.

RESULTS

Compared with ovulatory cycles (n = 467), sporadic anovulatory cycles (n = 42) had marginally higher total and significantly higher free T [mean 23.7 ng/dL (95% confidence interval [CI] 21.4-26.3) vs 21.6 ng/dL (95% CI 20.9-22.3), P = .08, and 0.36 ng/dL (95% CI 0.33-0.40) vs 0.32 ng/dL (95% CI 0.31-0.33), P = .02, respectively] during menses and also throughout the luteal phase (P < .01 for all). Women with higher T had elevated AMH concentrations, increased reporting of a history of acne requiring medical treatment, but not increased hirsutism.

CONCLUSIONS

Mechanisms of androgen-related ovulatory dysfunction that characterize PCOS in women with menstrual disturbances may occur across a continuum of T concentrations, including in eumenorrheic women without clinical hyperandrogenism.