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

Lindsey A Sjaarda; Sunni L Mumford; Kerri Kissell; Karen C Schliep; Ahmad Hammoud; Neil J Perkins; J Weck; Jean Wactawski-Wende; Enrique F Schisterman

doi:10.1210/jc.2013-3781

Reproductive Endocrinology · Ovarian Hormones

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

Sjaarda LA, Mumford SL, Kissell K, Schliep KC, Hammoud AO, Perkins NJ, Weck J, Wactawski-Wende J, Schisterman EF

Published June 2014 The Journal of clinical endocrinology and metabolism, 99(6), 2208-2216

DOI 10.1210/jc.2013-3781 PMID 24606085 PMC PMC4037725

RRM Academy Synopsis

Higher testosterone went with more missed ovulation in regular cycles

Higher testosterone went with more cycles without ovulation in women with regular periods. The study followed 259 healthy women with no reported infertility or PMOS (formerly PCOS) for 509 cycles. AMH, a marker of follicle count, also rose with testosterone.

Key Findings

The BioCycle Study followed 259 women for 509 cycles: 467 cycles with ovulation and 42 sporadic cycles without it.
Cycles without ovulation made up 2.4% of the lowest testosterone quartile (measured during menses) and 12.7% of the highest (P = .02).
Cycles without ovulation had higher free testosterone during menses (P = .02), and higher total and free testosterone throughout the luteal phase (P < .01).
AMH was higher in the higher testosterone quartiles, independent of age.
Cycles in the top quartile of both AMH and total testosterone were 26% without ovulation; top AMH alone, 13%; top testosterone alone, 3%; others, 5.5% (P < .001 across three groups).

Interpretation

The BioCycle Study followed women forward in time, so it shows association. The women were young and, on average, nonobese, and reported regular cycles and no known infertility or polyendocrine metabolic ovarian syndrome (PMOS), formerly polycystic ovary syndrome (PCOS). Progesterone and LH blood tests defined cycles without ovulation, and no ultrasound confirmed them. The women reported their own infertility and PCOS history, so the youngest group, with the highest testosterone, may hold undiagnosed cases. Hair growth scores did not differ by testosterone quartile. The authors suggest the pattern may run along a continuum that includes women with regular cycles.

RRM Context

The authors suggest that a history of regular periods is an imperfect way to find ovulation problems. Restorative reproductive medicine centers the ovulatory cycle and asks whether ovulation happened. The researchers used fertility monitors to time blood draws. The AMH test later proved to read low. The authors report that a sensitivity analysis with recalibrated AMH values changed no statistical significance in the AMH findings.

Our editorial summary of this paper, not the article's abstract.

Abstract

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.

Topics

Reproductive Endocrinology › Ovarian Hormones › Androgens · Menstrual Cycle › Cycle Disorders › Ovulatory Disturbances · Diagnostics › Hormone Testing › Serum Panels

Lindsey A Sjaarda, Sunni L Mumford, Karen C Schliep, Neil J Perkins, Enrique F Schisterman, Jean Wactawski-Wende

L Sjaarda, S Mumford, K Schliep, N Perkins, E Schisterman, J Wactawski-Wende

PMID 24606085 24606085 DOI 10.1210/jc.2013-3781 10.1210/jc.2013-3781 Sjaarda et al. 2014, Sjaarda 2014

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

Higher testosterone went with more missed ovulation in regular cycles

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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