Prolonging youth or prolonging perimenopause? Beware the Monkey’s Paw

Nanette Santoro, Sean D. Lawley, Mary D. Sammel, Joshua Johnson
In: Menopause · 2025 · vol. 32(10) , pp. 978–982 · doi:10.1097/gme.0000000000002590 · PMID:40460398 · W4410982081
review OA: closed CC0
Full text JSON View on OpenAlex View on PubMed View at publisher
⚙ AI-generated deep summary by claude@2026-06, 2026-06-17 · read from full text ⓘ

The paper discusses whether attempts to prolong ovarian functional lifespan—by delaying menopause or extending ovarian hormone production—could produce unintended adverse outcomes, using arguments and a mathematical model of ovarian follicle loss over time. It reviews the historical prevalence of amenorrhea, the morbidity associated with decades of menstrual cyclicity, the lack of demonstrated life-span benefit from ovarian steroid hormone treatment after natural menopause, and the possibility that current strategies aimed at delaying menopause could backfire by prolonging the menopause transition. The main caveat is that the paper is largely argumentative and modeling-based rather than presenting new empirical trial results. Relevance to endometriosis: it discusses prolonged ovarian/menstrual function and menopause transition dynamics as potential sources of morbidity, which can intersect with the hormonal milieu implicated in endometriosis, though the paper does not explicitly focus on endometriosis.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

OBJECTIVE: To discuss the potential for adverse consequences that could arise from the quest to prolong the functional life span of the human ovary. METHODS: A series of arguments are presented that: (a) question the dogma that monthly ovulatory menstrual cycles are critical for women's health; (b) review adverse consequences of decades of menstrual cyclicity; (c) review the evidence for a longevity benefit of ovarian steroid hormone treatment after the age at natural menopause has been achieved; and (d) utilize a mathematical model of ovarian follicle loss over time to raise the possibility that current strategies directed at delaying menopause might well backfire and in fact cause a woman to have a prolonged menopause transition. RESULTS: Regular, monthly menstrual cycles have not been the reality for women for most of history. Rather, when not pregnant, lactational amenorrhea and nutritionally based hypothalamic amenorrhea were the norm for reproductive-aged women. Moreover, monthly menstrual cycles cause substantial morbidity for women during their reproductive years. Providing steroid hormones after menopause has failed to demonstrate an increase in the female life span. Restoring ovarian follicles either surgically or medically has a high probability of causing women to spend more years of life in the menopause transition. CONCLUSIONS: Strategies to prevent or delay menopause would benefit from careful consideration of unintended consequences as they are implemented. Directing treatment trials to those with the greatest chance for benefit should be undertaken before adopting this type of treatment for a broader population.
Full text 1,656 characters · extracted from oa-doi-fallback · 4 sections · click to expand

Objective

To discuss the potential for adverse consequences that could arise from the quest to prolong the functional life span of the human ovary.

Methods

A series of arguments are presented that: (a) question the dogma that monthly ovulatory menstrual cycles are critical for women’s health; (b) review adverse consequences of decades of menstrual cyclicity; (c) review the evidence for a longevity benefit of ovarian steroid hormone treatment after the age at natural menopause has been achieved; and (d) utilize a mathematical model of ovarian follicle loss over time to raise the possibility that current strategies directed at delaying menopause might well backfire and in fact cause a woman to have a prolonged menopause transition.

Results

Regular, monthly menstrual cycles have not been the reality for women for most of history. Rather, when not pregnant, lactational amenorrhea and nutritionally based hypothalamic amenorrhea were the norm for reproductive-aged women. Moreover, monthly menstrual cycles cause substantial morbidity for women during their reproductive years. Providing steroid hormones after menopause has failed to demonstrate an increase in the female life span. Restoring ovarian follicles either surgically or medically has a high probability of causing women to spend more years of life in the menopause transition.

Conclusions

Strategies to prevent or delay menopause would benefit from careful consideration of unintended consequences as they are implemented. Directing treatment trials to those with the greatest chance for benefit should be undertaken before adopting this type of treatment for a broader population.

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2025) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

References (18)

Source provenance

openalex
last seen: 2026-05-13T18:32:35.295212+00:00
unpaywall
last seen: 2026-06-13T06:42:57.164913+00:00
License: CC0 · commercial use OK