Menopause

Two double-blind, placebo-controlled RCTs of standardised root extracts report benefit for menopausal/perimenopausal symptoms: a 120-day trial (CL22205, 200 mg/day, n=50) cut Menopause Rating Scale and hot-flush scores and shifted FSH/LH/AMH ^{39Reference 39Yadav P et al. · 2025RCTA standardized Asparagus racemosus root extract improves hormonal balance and menstrual health and reduces vasomotor symptoms — randomised placebo-controlled trialView study →}, and a multicentre RCT (n=70) reduced hot flushes, night sweats, insomnia, anxiety and vaginal dryness ^{40Reference 40Gudise VS et al. · 2024RCTEfficacy and safety of Shatavari root extract for the management of menopausal symptoms — double-blind, multicenter, randomised controlled trialView study →}.

Phytoestrogenic steroidal saponins on the sarsasapogenin aglycone give a plausible mechanism. Both trials are small, industry-sponsored, on proprietary standardised extracts — no whole-root data and no head-to-head against hormone therapy.

Menopause is black cohosh’s main indication, and the evidence conflicts. A 2023 pairwise meta-analysis (22 RCTs, n=2,310) found significant but small improvement in overall menopausal symptoms and hot flashes (Hedges’ g ≈ 0.32) ^{1Reference 1Sadahiro et al. · 2023Meta-analysisBlack cohosh extracts in women with menopausal symptoms: an updated pairwise meta-analysisView study →}, and the iCR isopropanolic-extract review reported efficacy comparable to low-dose transdermal estradiol ^{2Reference 2Castelo-Branco et al. · 2021Meta-analysisReview & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms — an updateView study →}.

Against this, the 2012 Cochrane review (16 RCTs, n=2,027) found no significant difference from placebo ^{3Reference 3Leach et al. · 2012Systematic reviewBlack cohosh (Cimicifuga spp.) for menopausal symptoms — Cochrane systematic review of randomised controlled trialsView study →}, and two rigorous North American RCTs in breast-cancer populations were flatly null ^{4,5Reference 4Pockaj et al. · 2006RCTPhase III double-blind, randomised, placebo-controlled crossover trial of black cohosh for hot flashes (NCCTG N01CC1)View study →Reference 5Jacobson et al. · 2001RCTRandomised trial of black cohosh for hot flashes among women with a history of breast cancerView study →}. Most positive data cluster on one manufacturer-sponsored standardised extract and do not generalise to teas/tinctures.

Mechanism is serotonergic/neuroendocrine, not classically estrogenic ^{6,7Reference 6Powell et al. · 2008In vitroIn vitro serotonergic activity of black cohosh and identification of Nω-methylserotonin as a potential active constituentView study →Reference 7Overk et al. · 2008In vitroHigh-content screening and mechanism-based evaluation of estrogenic botanical extracts (SERM-like activity of black cohosh) — in vitroView study →}. Mood/anxiety benefit is inconsistent (null in the 2023 MA) ^{1Reference 1Sadahiro et al. · 2023Meta-analysisBlack cohosh extracts in women with menopausal symptoms: an updated pairwise meta-analysisView study →}. Black cohosh carries a rare, idiosyncratic risk of hepatotoxicity.

A 42-day RCT of a standardised seed extract (250 mg twice daily) in perimenopausal women reduced hot flushes, night sweats, insomnia and depression scores and shifted estradiol, progesterone and FSH toward premenopausal balance with no adverse safety-parameter changes ^{14Reference 14Khanna et al. · 2020RCTEfficacy of a novel extract of fenugreek seeds in alleviating vasomotor symptoms and depression in perimenopausal women: A randomized, double-blinded, placebo-controlled studyView study →}; a separate RCT found fenugreek vaginal cream comparable to ultra-low-dose conjugated estrogen for atrophic vaginitis on the Vaginal Maturation Index ^{15Reference 15Safary et al. · 2020RCTComparison of the Effects of Fenugreek Vaginal Cream and Ultra Low-Dose Estrogen on Atrophic Vaginitis — randomized controlled clinical trialView study →}. The plausible driver is diosgenin-linked phytoestrogenic activity.

The evidence is two small single-site trials of different preparations (oral vs vaginal), no replication and no long-term endometrial safety data.

Hops carries 8-prenylnaringenin, the most potent plant oestrogen yet identified, which competes with 17β-estradiol at both ERα and ERβ ^{16,17Reference 16Milligan SR et al. · 2000In vitroThe endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids — [in vitro]View study →Reference 17Tronina T et al. · 2020ReviewFlavonoids as Phytoestrogenic Components of Hops and Beer — [review]View study →}; this biology drove at least four RCTs of 8-PN-standardised extracts on menopausal/vasomotor symptoms ^{18,19,20,21Reference 18Heyerick A et al. · 2006RCTA first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts — [randomized]View study →Reference 19Erkkola R et al. · 2010RCTA randomized, double-blind, placebo-controlled, cross-over pilot study on the use of a standardized hop extract to alleviate menopausal discomforts — [randomized]View study →Reference 20Aghamiri V et al. · 2016RCTThe effect of Hop (Humulus lupulus L.) on early menopausal symptoms and hot flashes: A randomized placebo-controlled trial — [randomized]View study →Reference 21Kim HI et al. · 2021RCTEfficacy and Safety of a Standardized Soy and Hop Extract on Menopausal Symptoms: A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial — [randomized]View study →}.

The trials conflict. One 12-week trial beat placebo on the Kupperman index at 6 but not 12 weeks with no dose-response ^{18Reference 18Heyerick A et al. · 2006RCTA first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts — [randomized]View study →}, a crossover saw placebo do slightly better ^{19Reference 19Erkkola R et al. · 2010RCTA randomized, double-blind, placebo-controlled, cross-over pilot study on the use of a standardized hop extract to alleviate menopausal discomforts — [randomized]View study →}, while two others were positive ^{20,21Reference 20Aghamiri V et al. · 2016RCTThe effect of Hop (Humulus lupulus L.) on early menopausal symptoms and hot flashes: A randomized placebo-controlled trial — [randomized]View study →Reference 21Kim HI et al. · 2021RCTEfficacy and Safety of a Standardized Soy and Hop Extract on Menopausal Symptoms: A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial — [randomized]View study →} — heavily shaped by placebo response, and tied to specific standardised extracts, not a tea or ordinary tincture.

Four RCTs pooled in a 2011 systematic review all favoured maca on menopausal symptom scores (Kupperman, Greene) in peri-/postmenopausal women, though the review stressed small numbers, modest quality and unproven safety ^{22Reference 22Lee et al. · 2011Systematic reviewMaca (Lepidium meyenii) for treatment of menopausal symptoms: a systematic reviewView study →}. A crossover RCT (n=14, 3.5 g/day) lowered Greene Climacteric and psychological scores with no change in oestradiol, FSH, LH or SHBG, and assays confirmed no oestrogenic/androgenic activity ^{23Reference 23Brooks et al. · 2008RCTBeneficial effects of Lepidium meyenii (Maca) on psychological symptoms and measures of sexual dysfunction in postmenopausal women are not related to oestrogen or androgen content — randomised controlled trialView study →}; a 2018 phytoestrogen meta-analysis also placed maca among plants improving sexual function in menopausal women ^{24Reference 24Najaf Najafi et al. · 2018Meta-analysisEffect of phytoestrogens on sexual function in menopausal women: a systematic review and meta-analysisView study →}. Symptom relief via a non-hormonal (HPA/HPG-axis) route ^{25,26Reference 25Zhang et al. · 2014AnimalEffect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomised rats — animal modelView study →Reference 26Meissner et al. · 2006AnimalHormone-balancing effect of pre-gelatinised organic maca (Lepidium peruvianum Chacon): biochemical and pharmacodynamic study on ovariectomised rats — animal modelView study →}; trials remain small, heterogeneous in preparation/dose, and long-term safety in this population is unestablished.

Menopause is red clover’s main modern use. A 2026 GRADE-assessed meta-analysis of nine RCTs found a significant small-to-moderate reduction in hot-flush frequency (SMD −0.446) ^{27Reference 27Jiang et al. · 2026Meta-analysisThe effectiveness of red clover on hot-flash in menopausal women: a GRADE-assessed systematic review and meta-analysisView study →}, and a 2021 meta-analysis found −1.73 flushes/day, strongest at ≥80 mg/day and with biochanin-A-rich formulations ^{28Reference 28Kanadys et al. · 2021Meta-analysisEvaluation of clinical meaningfulness of red clover (Trifolium pratense L.) extract to relieve hot flushes and menopausal symptoms — systematic review and meta-analysis of randomised controlled trialsView study →}; a Promensil-80 mg meta-analysis reported ~3.6 fewer flushes/day ^{29Reference 29Myers et al. · 2017Meta-analysisEffects of a standardised extract of Trifolium pratense (Promensil) at 80 mg in the treatment of menopausal hot flushes: a systematic review and meta-analysisView study →}.

Against this, the 2013 Cochrane review found no conclusive evidence, with a placebo response of 1–59% ^{30Reference 30Lethaby et al. · 2013Systematic reviewPhytoestrogens for menopausal vasomotor symptoms — Cochrane systematic reviewView study →}, and individual RCTs split positive/null ^{31,32,33Reference 31Shakeri et al. · 2015RCTEffectiveness of red clover in alleviating menopausal symptoms: a 12-week randomised controlled trialView study →Reference 32Del Giorno et al. · 2010RCTEffects of Trifolium pratense on the climacteric and sexual symptoms in postmenopause women — randomised controlled trialView study →Reference 33Geller et al. · 2009RCTSafety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomised controlled trialView study →}. The mechanism is weak ERβ-preferring isoflavones.

The effect belongs to standardised extracts (40–160 mg isoflavones/day), not tea or whole flower; high heterogeneity + large placebo effect; a menopausal anxiety/mood crossover RCT is also positive ^{34Reference 34Lipovac et al. · 2010RCTImprovement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts — randomised crossover trialView study →}.

A 2023 systematic review/meta-analysis of four trials (n=310) found Salvia officinalis significantly reduced hot-flush frequency vs placebo (severity NS); the largest single study (open-label, n=69) reported falling flush intensity/frequency over 8 weeks, and an ADT-patient pilot agreed, via mild oestrogenic flavonoid activity ^{35,36,37,38Reference 35Bommer et al. · 2011Clinical trialFirst-time proof of sage’s tolerability and efficacy in menopausal women with hot flushes — clinical trialView study →Reference 36Moradi et al. · 2023Meta-analysisThe effect of Salvia officinalis on hot flashes in postmenopausal women: a systematic review and meta-analysisView study →Reference 37Vandecasteele et al. · 2012Clinical trialEvaluation of the efficacy and safety of Salvia officinalis in controlling hot flashes in prostate cancer patients treated with androgen deprivation — clinical trialView study →Reference 38Rahte et al. · 2013In vitroSalvia officinalis for hot flushes: towards determination of mechanism of activity and active principles — in vitroView study →}.

A classic Western women’s-health herb taken across the menopausal transition for its action on the pituitary axis; its trials are in premenstrual/luteal complaints, not menopause, so the menopausal use rests on tradition.

Lemon balm is used traditionally to ease the low mood, irritability and disturbed sleep that accompany menopause; this rests on its general calming reputation rather than a menopause-specific trial.

Menopause is the one dong quai indication with human RCTs, and they are negative. A 24-week double-blind, placebo-controlled trial in 71 postmenopausal women found dong quai alone produced no change in vasomotor flushes, endometrial thickness or vaginal cell maturation, and no oestrogenic effect ^{8Reference 8Hirata et al. · 1997RCTDoes dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled randomised trial (RCT)View study →}; a second RCT in 22 men with androgen-deprivation hot flashes was likewise negative ^{9Reference 9Al-Bareeq et al. · 2010RCTDong Quai for hot flashes in men on androgen-deprivation therapy: randomised double-blind placebo-controlled trial (RCT)View study →}.

Positive vasomotor results exist only for multi-herb products containing dong quai ^{10,11,12Reference 10Haines et al. · 2008RCTA randomised, double-blind, placebo-controlled study of Dang Gui Buxue Tang on menopausal symptoms — RCTView study →Reference 11Rotem et al. · 2007RCTPhyto-Female Complex for hot flushes, night sweats and sleep quality: randomised, controlled, double-blind pilot study (RCT)View study →Reference 12Kupfersztain et al. · 2003RCTImmediate effect of Angelica sinensis and Matricaria chamomilla (Climex) for hot flushes — placebo-controlled RCTView study →}, so benefit cannot be attributed to the herb itself, and a 2026 systematic review of non-soy oral herbal supplements reiterates the weak evidence base ^{13Reference 13Jing et al. · 2026Systematic reviewThe effectiveness of non-soy oral herbal supplements for menopausal symptoms — systematic review. https://pubmed.ncbi.nlm.nih.gov/42451042/View study →}.