Fourfold increase in ovulatory cycles
Modern women experience roughly four times as many ovulatory cycles as women 200 years ago, likely driving rising endometriosis prevalence.
Snapshot · The Peter Attia Drive
#397 ‒ Endometriosis and adenomyosis: diagnosis, fertility, reproductive aging, and emerging treatments | Renato Tomioka, M.D., Ph.D.
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Jun 22, 2026
Where this was said
The biology of endometriosis: estrogen dependence, progesterone resistance, and tumor-like growth mechanisms
At 9:13 · chapter starts 9:03
Tomioka draws a striking evolutionary comparison: a woman 200 years ago had menarche at 16, her first pregnancy at 20, breastfed multiple children, and experienced around 100 lifetime ovulatory cycles. A modern woman — menarche at 12, first pregnancy at 30 or later, fewer children, less breastfeeding — may have 400 or more. That fourfold increase in retrograde menstrual events is, in his view, the primary reason endometriosis prevalence is genuinely rising, not just better-detected. [1] — Renato Tomioka "Fourfold increase in ovulatory cycles: Modern women experience roughly four times as many ovulatory cycles as women 200 years ago, likely d…" 09:13 At the molecular level, endometriosis is driven by two interlocking abnormalities: the lesions overexpress aromatase, producing their own estrogen fuel independently of the ovaries, and they are resistant to progesterone, the hormone normally tasked with keeping endometrial tissue in check. This double dysfunction explains why blocking ovarian hormone production is often insufficient. Most striking is Tomioka's observation that up to 37% of deep infiltrating lesions carry somatic oncogenic mutations in KRAS and PIK3CA — giving them cancer's growth machinery — yet fibrosis and adhesions prevent metastasis. He uses a vivid analogy: a 1,000-horsepower Formula 1 engine installed in a golf cart. The power is there; the chassis can't use it.
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