Narrower indications

Recorded under menopause, with no page of their own: menopausal vasomotor symptoms, vulvovaginal atrophy, postmenopausal vulvovaginal atrophy, dyspareunia due to menopausal vulvovaginal atrophy, postmenopausal osteoporosis, postmenopausal hypoactive sexual desire disorder, endometrial hyperplasia, carotid atherosclerosis in recently postmenopausal women. Their evidence is graded on this page rather than split across pages that would each hold a single row.

Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. DHEA

   human RCT Direct outcome Approved for this condition

   Who was studied

   postmenopausal women with moderate to severe dyspareunia due to vulvar and vaginal atrophy, in two 12-week placebo-controlled trials of the 6.5 mg prasterone vaginal insert, n=255 and n=558.

   The FDA approved the prasterone 6.5 mg vaginal insert (Intrarosa, NDA 208470) on 17 November 2016 and the European Commission authorised it on 8 January 2018, both for moderate to severe dyspareunia due to menopausal vulvar and vaginal atrophy; the registrational trials measured dyspareunia severity (change -1.27 vs -0.87, p=0.0132; -1.42 vs -1.06, p=0.0002) alongside vaginal superficial cells, parabasal cells and pH. That approval belongs to the vaginal insert and to that single indication, and does not transfer to oral over-the-counter DHEA, for which no regulator has approved any product, established any dose, or reviewed any safety labelling. The strongest randomised evidence on file for oral DHEA is a meta-analysis of 10 placebo-controlled trials in women with adrenal insufficiency reporting a pooled quality-of-life effect size of 0.21, which the authors described as small and possibly trivial; no trial on file measured any menopausal outcome of oral DHEA.

   Source DailyMed — the FDA label 3 primary sources read for this row

2. Estradiol

   human RCT Direct outcome Approved for this condition

   Who was studied

   postmenopausal and otherwise hypoestrogenic women; the FDA labelling states no n or trial duration for the vasomotor efficacy data. The one randomised trial read in full, ELITE, enrolled 643 healthy postmenopausal women on oral 1 mg/day for a median of about 5 years, stratified by time since menopause.

   The FDA has approved estradiol for moderate to severe vasomotor symptoms of the menopause, for moderate to severe vulvar and vaginal atrophy, and for prevention of postmenopausal osteoporosis; the first two are patient-reported menopausal symptoms and the third is a bone-density indication. ELITE separately measured carotid intima-media thickness, which progressed more slowly than placebo only in women randomised within 6 years of menopause, and measured coronary atherosclerosis by CT, which did not differ significantly from placebo in either stratum. The labelling carries a boxed warning covering endometrial cancer, cardiovascular disorders, probable dementia and breast cancer, and states that oestrogens should not be used for the prevention of cardiovascular disease.

   Source DailyMed — the FDA label 3 primary sources read for this row

3. Progesterone

   human RCT Direct outcome Approved for this condition

   Who was studied

   non-hysterectomised postmenopausal women receiving conjugated oestrogens, for the labelled endometrial-hyperplasia indication. The randomised vasomotor trial enrolled a different population: perimenopausal women, n=189, 4 months, 300 mg oral micronised progesterone at bedtime.

   The FDA-approved menopausal indication is prevention of endometrial hyperplasia in non-hysterectomised postmenopausal women taking conjugated oestrogens, and the endpoint there is endometrial histology, not a menopausal symptom. For vasomotor symptoms the 2023 Phase III Canada-wide randomised placebo-controlled trial (Sci Rep, PMC10241804) missed its primary endpoint: rate ratio 0.79, 95% CI 0.54-1.15, p=0.222, with secondary measures of perceived night sweats and sleep favouring progesterone. That trial enrolled perimenopausal women; the other randomised vasomotor trial in postmenopausal women (Hitchcock and Prior, Menopause 2012) was paywalled and was not read, so no postmenopausal vasomotor result is on file here.

   Source DailyMed — the FDA label 3 primary sources read for this row

4. PT-141

   human RCT Direct outcome Not approved for this condition

   Who was studied

   premenopausal women only, in two identical Phase III randomised double-blind placebo-controlled trials (NCT02333071, NCT02338960) and a Phase II dose-finding trial (NCT01382719); postmenopausal women were outside the enrolled population in every one of them.

   Bremelanotide is FDA-approved (Vyleesi, NDA 210557, 21 June 2019) for acquired, generalised hypoactive sexual desire disorder in PREMENOPAUSAL women, and the registrational trials measured desire and distress scores in that population. That approval sits in an adjacent population and is not an approval for postmenopausal hypoactive sexual desire disorder or for any other menopausal indication. No trial in postmenopausal women is on file, so nothing here establishes what the compound does after the menopause.

   Source ClinicalTrials.gov 3 primary sources read for this row

5. Testosterone

   human RCT Direct outcome Off-label use

   Who was studied

   postmenopausal women diagnosed with hypoactive sexual desire disorder after biopsychosocial assessment, pooled from blinded randomised placebo-controlled trials of at least 12 weeks (Islam 2019); no randomised data beyond about two years, and no breast cancer or cardiovascular endpoint data in women, are on file.

   In postmenopausal women with hypoactive sexual desire disorder, randomised trials measured satisfying sexual events and reported an average increase of about one per month, with changes in desire, arousal, orgasm, pleasure and sexual responsiveness. The same body of randomised evidence measured cognition, bone mineral density at spine, hip and femoral neck at 12 months, depressed mood and general wellbeing, and lean mass, total fat and muscle strength, and demonstrated no effect on any of them in women; the 2019 Global Consensus Position Statement records the evidence for those outcomes as insufficient. No testosterone product is FDA-approved for women, so use in this population is off-label in male formulations at roughly one tenth the male replacement dose, and reported excess adverse effects were acne and hirsutism.

   Source DOI 3 primary sources read for this row

Checked, and nothing recorded

11 compounds were checked against menopause and produced no gradeable row.

• Collagen Peptides — checked, no row on file
• Epitalon — checked, no row on file
• GHK-Cu — checked, no row on file
• hCG — checked, no row on file
• Kisspeptin-10 — checked, no row on file
• MOTS-c — checked, no row on file
• Oxytocin — checked, no row on file
• Selank — checked, no row on file
• Semax — checked, no row on file
• SS-31 — checked, no row on file
• Thymosin alpha-1 — checked, no row on file

A compound is here because someone looked and the sources did not support a row — not because nobody looked. Under the rubric, uncertainty resolves to no row, and a row resting on a vendor page or a clinic blog is worse than no row at all.