Polycystic ovary syndrome and menopausal transition: Hormonal dynamics, phenotypic evolution, and ethnic considerations

Sir,

We read with great interest the recent article by Lavi et al. ¹ demonstrating that women with polycystic ovary syndrome (PCOS) are less likely to reach late peri‐postmenopause by age 46 and report fewer menopausal symptoms. This study provides compelling evidence that PCOS delays reproductive aging. While representing a major advance, several aspects merit further consideration.

PCOS is a dynamic endocrine syndrome whose phenotype evolves across the lifespan. The Rotterdam criteria at age 31 capture a single snapshot, yet oligoovulation improves with aging while hyperandrogenism persists. Evidence shows that although most women with PCOS experience improved menstrual regularity by their mid‐40s, serum AMH, total testosterone, free androgen index, and DHEAS remain significantly higher than in controls. ² Thus, while clinical features may partially resolve, hyperandrogenism persists. The original analysis could not fully capture those with possible phenotypic resolution by midlife. Persistent versus resolved PCOS may have divergent effects on ovarian aging, warranting longitudinal tracking.

The relationship between PCOS and menopausal symptoms may be more nuanced than a simple reduction. AMH is markedly higher in PCOS even at age 46. Importantly, serum AMH in PCOS remains relatively stable with advancing age, unlike the expected decline in ovulatory women. ³ This sustained elevation reflects greater ovarian reserve and inhibits follicular recruitment, attenuating the rise of follicle‐stimulating hormone. ³ Consequently, slower follicular depletion combined with gonadotropin modulation could delay the entire menopausal transition. Indeed, PCOS is associated with a delayed menopause by approximately 2 years, and AMH levels are negatively correlated with vasomotor symptom severity. ⁴ Reduced symptom burden at age 46 may therefore reflect a right‐shifted trajectory rather than a genuine reduction. If symptoms are delayed, clinicians should consider intensified counseling when these women enter their early 50s.

The metabolic milieu of PCOS complicates symptom interpretation. Women with PCOS have higher rates of obesity, insulin resistance, and mood disorders, all affecting sleep quality and well‐being. ¹ The lower prevalence of sleep disturbance in PCOS may be influenced by pharmacological treatment of coexisting depression or anxiety. Future research should incorporate validated instruments for depression and anxiety alongside menopausal symptom questionnaires.

Generalizability to non‐European populations merits investigation. PCOS phenotypes differ across ethnic groups, yet most normative AMH data derive from European ancestry populations. ⁵ Research in Samoan women, a population with high obesity prevalence, has shown that AMH levels and their age‐related decline are similar to those in other populations, and AMH is not associated with BMI or insulin resistance. ⁵ Estimated PCOS prevalence in this cohort is at the lower end of the global range. ⁵ These findings challenge assumptions linking high obesity rates to higher PCOS prevalence or altered AMH trajectories, underscoring the need for population‐specific reference ranges.

We commend the authors for providing the largest evidence to date on this topic. Building on these strengths, future studies could track PCOS status longitudinally, extend follow‐up beyond age 50, account for psychiatric comorbidity, and validate findings in diverse cohorts.

CONFLICT OF INTEREST STATEMENT

The author has no conflicts of interest relevant to this letter.