Divergent effects of hyperandrogenemia on the female reproductive neuroendocrine axis under different physiological conditions.

Review of clinical and preclinical evidence

“This review synthesizes current clinical and preclinical evidence to compare distinct models of hyperandrogenemia with respect to the female HPG axis and aims to illuminate how endogenous and exogenous androgens with different features differentially alter female neuroendocrine function.”

Females with hyperandrogenemia, including those with PMOS, anabolic substance abuse, or receiving gender-affirming testosterone therapy, and preclinical rodent models

“This review seeks to synthesize recent findings from clinical studies and preclinical rodent models to examine how endogenous versus exogenous androgen exposure modulates the female neuroendocrine HPG axis.”

Exogenous androgen exposure at male physiological levels suppresses LH secretion and disrupts ovulatory cycling

“In testosterone therapy and anabolic substance abuse, high exogenous androgen exposure in or above the male physiological range typically suppresses LH secretion and disrupts ovulatory cycling, mimicking enhanced negative feedback on the HPG axis.”

Endogenous androgen elevations in PMOS are associated with increased LH secretion, acyclicity, and anovulation

“Conversely, in PMOS, endogenous elevations in T, high for a female but below the male physiological range, are associated with increased LH secretion, acyclicity, and anovulation.”

Divergent LH outcomes may reflect differences in androgen source, concentration, and timing of exposure

“The mechanisms underlying these divergent LH outcomes remain unclear but may reflect, in part, differences in the source of androgens (exogenous vs. endogenous), circulating androgen concentrations, and development timing and/or duration of androgen exposure.”

Small sample sizes in clinical studies reduce statistical power and make generalization difficult

“A challenging limitation of the current clinical literature for androgen effects on LH pulses is small sample sizes, which reduces statistical power and makes it difficult to generalize variable findings across heterogeneous populations.”