Progesterone and synthetic progestins belong to the broader progestogen category but are not identical compounds. In menopausal HRT, a central role is protection of the endometrium when systemic estrogen is used in someone with a uterus. The PEPI trial and product-specific prescribing information support this role. Source ↗ · US progesterone label ↗
Women: endometrial protection
PEPI found more endometrial hyperplasia with unopposed estrogen, while the tested estrogen-plus-progestogen regimens protected against these changes. Evidence must remain tied to the preparation and regimen studied. Source ↗
Women: symptoms and sleep research
A 2023 Phase 3 perimenopause trial did not find a statistically significant difference in its primary vasomotor-symptom score. Participants reported improvements in perceived night sweats and sleep. Primary and secondary findings should be distinguished. Source ↗
Men: evidence boundary
This initial screened library has not identified a pivotal trial supporting routine progesterone replacement in men. Menopausal endometrial-protection findings must not be extrapolated to men. This is a search limitation, not proof that no research exists.
Recent research plus older foundations · Trials, observational studies and product labels are separately identified · Phases shown only when verified
2023Phase 3 · randomized placebo-controlled trial
189 participants. Primary symptom-score difference was not statistically significant; perceived night sweats and sleep improved.
Abstract / record screened; full-text, conflicts and current correction checks pending.
2019Phase 1 and Phase 3 pharmacokinetic / clinical data
Oral formulation-specific data; related to REPLENISH, not independent efficacy confirmation.
Abstract / record screened; full-text, conflicts and current correction checks pending.
FOUNDATIONAL STUDY2018Phase 3 · randomized trial
Why it matters: Pivotal evidence for this fixed oral combination.
Combination product; cannot isolate progesterone’s contribution to all outcomes.
Abstract / record screened; full-text, conflicts and current correction checks pending.
FOUNDATIONAL STUDY2012Randomized placebo-controlled trial
Why it matters: Early controlled symptom-efficacy study; different population from the 2023 trial.
133 randomized participants; selected healthy early-postmenopausal population. NCT00152438.
Abstract / record screened; full-text, conflicts and current correction checks pending.
2000Small clinical study
27 women; route-specific evidence boundary, not a verdict on all possible formulations.
Abstract / record screened; full-text, conflicts and current correction checks pending.
FOUNDATIONAL STUDY1996Randomized trial
Why it matters: Established the importance of endometrial protection with unopposed estrogen.
596 women in the endometrial study; tested cyclic micronized progesterone and synthetic progestin regimens.
Abstract / record screened; full-text, conflicts and current correction checks pending.
FOUNDATIONAL STUDY2002Randomized trial
Why it matters: Landmark combination-therapy risks; must not be mislabelled as a trial of progesterone.
MPA is a synthetic progestin, not micronized progesterone.
Abstract / record screened; full-text, conflicts and current correction checks pending.