Duffy · Human reproduction update 2015 · narrative review · n=?

Novel contraceptive targets to inhibit ovulation: the prostaglandin E2 pathway.

Cited 126 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing mechanistic, preclinical animal (macaque), and human literature

PubMed 26025453 · doi:10.1093/humupd/dmv026 · record verified 2026-08-26

What was done

This narrative review synthesized literature published between 1987 and 2014 examining the prostaglandin E2 (PGE2) synthesis-metabolism-transport pathway during ovulation. It evaluated mechanistic studies in primary ovarian cells and cell lines, in vivo ovulation and breeding experiments in macaques, and human case reports and clinical studies evaluating cyclooxygenase/PTGS2 (COX-2) inhibitors for ovulation suppression.

What was found

The abstract reports no numerical data or statistical effect sizes. Qualitatively, LH triggers follicular expression of PGE2 synthesis, transport, and metabolic machinery. PTGS2 inhibitors reduced ovulation rates in women and decreased cumulus expansion, oocyte release, follicle rupture, oocyte maturation, and fertilization in macaques. In breeding macaques, PTGS2 inhibition reduced pregnancy rates when given as emergency contraception, but failed to prevent pregnancy when administered to simulate monthly contraceptive use.

Why it matters

It defines the PGE2 pathway as a potential non-hormonal target for contraception, demonstrating that while single PTGS2 inhibitors may have utility for emergency contraception, multi-target disruption across PGE2 synthesis, transport, and metabolism is likely required for regular monthly contraception.

Limits

The review is narrative rather than systematic, with no reported search strategy, study counts, or meta-analytic estimates. The abstract reports no quantitative effect sizes. Key contraceptive efficacy findings rely largely on non-human primate models, and monotherapy was ineffective for routine monthly contraception.

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