Er Xian Decoction and Menopause

Table of Contents

1. Six Herbs Cooked as One Formula
2. The Traditional Picture It Was Built For
3. The 2013 Hong Kong Placebo-Controlled Trial
4. What the Systematic Reviews Concluded
5. Bone Density After Menopause
6. Laboratory and Animal Findings
7. Estrogen-Like Activity and Estrogen-Sensitive Tissues
8. Safety Findings and Liver-Injury Reports
9. What Is Not Known
10. Key Research Papers
11. Connections
12. Featured Videos

Six Herbs Cooked as One Formula

The 2019 systematic review by Wang and colleagues lists the formula’s six ingredients by their Chinese pharmacopoeia names, and notes that all six are recorded in the Chinese Pharmacopoeia:

• Rhizoma Curculiginis — the rhizome of curculigo (Curculigo orchioides), called Xian Mao in Chinese.
• Herba Epimedii — Epimedium, called Xian Ling Pi or Yin Yang Huo. Xian Mao and Xian Ling Pi are the two “Xian” herbs the formula is named after.
• Radix Morindae Officinalis — the root of Morinda officinalis, called Ba Ji Tian.
• Radix Angelicae Sinensis — Chinese angelica root, the herb sold in the West as dong quai.
• Cortex Phellodendri — phellodendron bark.
• Rhizoma Anemarrhenae — the rhizome of anemarrhena.

A 2026 review in Phytomedicine by Chen and colleagues gives the same six herbs and credits the formula to Professor Bo-Ne Zhang in the 1950s, developed for managing menopausal syndrome. The same review reports that chemical studies have identified 128 compounds in the decoction, among them alkaloids, flavonoids, phenolic acids and terpenes. Quality control relies on measuring marker compounds such as icariin (the best-known Epimedium flavonoid) and berberine, and the review notes that the extraction method significantly changes how much of each compound ends up in the finished product.

A 2015 computer-based analysis from the University of Hong Kong took a wider net. Searching two traditional-medicine chemistry databases, it listed 721 compounds in the formula’s herbs, of which 63 passed standard filters for oral absorption and drug-likeness, and 20 were linked by the software to pathways or genes associated with menopause. That is a prediction from databases, not a measurement in people, but it shows the basic problem every researcher on this formula faces: there is no single active ingredient, and two batches of “Er Xian Decoction” made by different methods may not contain the same mixture.

The formula is also adapted in practice. Several studies on this page tested “modified” versions with an extra herb added, and the 2026 review describes the formula and its modifications together. A result for one version is not automatically a result for another.

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The Traditional Picture It Was Built For

The traditional account below is tradition, reported as such; it is not evidence that the formula works.

A 2007 introduction to the formula in the Chinese Journal of Integrative Medicine describes Er Xian Tang as a formula developed for menopausal syndrome in women, and reports that over the following 50 years practitioners extended it to many chronic diseases. In the language of Chinese medicine, the patterns it is given for are described as Shen (kidney) yin-yang deficiency, yin deficiency with flourishing yang, and disharmony of the Chong and Ren meridians — channels that traditional theory associates with menstruation and reproduction.

In plain terms, the traditional picture is a woman around the menopause who is at once depleted and overheated: tired and cold in some respects, with hot flushes and sweats in others. In the traditional explanation, the warming herbs (curculigo, Epimedium and morinda) address the depletion, Chinese angelica nourishes the blood, and the two cooling herbs (phellodendron and anemarrhena) temper the heat. The Traditional Use in Chinese Medicine article sets out this design in more detail.

The 2007 article also reports that experimental studies have found effects on the hypothalamus–pituitary–target-gland axis (the brain-to-gland hormone chain that controls the ovaries), on immune function and on free-radical metabolism. Those are laboratory findings and are described in their own section below.

The 2026 review lists the conditions the formula is now applied to beyond menopause, among them osteoporosis, premature ovarian failure and high blood pressure. A 2019 review of Chinese herbal medicine for high blood pressure after menopause found that Er Xian Decoction was the formula prescribed most often in the trials it collected (see the reviews section below).

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The 2013 Hong Kong Placebo-Controlled Trial

The single most informative human study is a randomised, double-blind, placebo-controlled trial run by the School of Chinese Medicine at the University of Hong Kong and published in the journal Menopause in 2013 by Zhong and colleagues.

Who took part and what was measured

• Participants: 108 perimenopausal women in Hong Kong (women in the years around the final period), all with a total score of 28 or higher on the Menopause Rating Scale, a standard questionnaire of menopausal symptoms.
• Length: 12 weeks of treatment, with a follow-up 3 months after treatment ended.
• Main outcome: the frequency and severity of hot flushes.
• Other outcomes: the Menopause Rating Scale total, the Menopause-Specific Quality of Life questionnaire, and blood hormone levels.
• Completion: 101 of the 108 women finished the study.

What it found

• Hot-flush frequency: the average fell from 5.8 to 2.2 in the Er Xian Decoction group and from 5.0 to 2.4 in the placebo group. The difference between groups was statistically significant (P = 0.04).
• Hot-flush score (combining frequency and severity): fell from 19.6 to 4.9 on the formula and from 16.6 to 7.0 on placebo (P = 0.02).
• Overall menopausal symptoms: the Menopause Rating Scale total improved more on the formula than on placebo (P = 0.03).
• Quality of life: the Menopause-Specific Quality of Life score improved more on the formula (P < 0.01).
• Hormones: blood hormone levels did not differ between the formula group and the placebo group.
• Safety: there were no serious adverse events, and blood counts, kidney function and liver function stayed within the normal range before and after treatment.

The authors concluded that the formula was superior to placebo in reducing the frequency and severity of hot flushes and in improving menopausal symptoms, and that it was well tolerated over the study period.

Reading the result carefully

Three features of the trial matter for how far the result reaches.

• The placebo group improved a great deal too. Hot flushes fell sharply in both groups. The formula’s advantage is the gap between the two groups, not the whole drop seen in the treated women.
• The hormone result is a null result. Blood hormone levels were no different from placebo, so the trial gives no human evidence that the formula worked by raising estrogen. How it might work in people remains unknown.
• It is one trial in one city. A single 12-week trial of 108 women is a starting point. In the 2019 review of 16 trials, it is the one placebo comparison the abstract reports.

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What the Systematic Reviews Concluded

Three systematic reviews have pooled the menopause trials. Their conclusions are consistent: the trials tend to report benefit, and their quality is too low to rely on.

The 2008 review

Chen and colleagues at the University of Hong Kong searched seven Chinese and English databases and retrieved 154 articles. Only 5 randomised trials, with 677 participants, met their criteria. Pooled together, the trials showed that the formula relieved at least one menopausal symptom more than the comparison treatments did, and did better than non-hormonal treatments; the authors found no significant difference between the formula and menopausal hormone therapy. Because of the low quality of the studies, they concluded that more randomised trials were needed before an evidence-based recommendation about the formula could be made.

The 2019 review of 16 trials

Wang and colleagues from Wenzhou Medical University searched eight databases up to July 2018 and set a stricter entry bar: only randomised trials scoring 7 or more on a Cochrane Back Review Group risk-of-bias scale were included. They found 16 eligible studies with 1,594 participants. The comparison treatments were placebo, hormone replacement therapy, hormones plus non-hormonal drugs, non-hormonal drugs, and no treatment.

• Against placebo: one study (the Hong Kong trial above) showed that the formula improved hot-flush scores, Menopause Rating Scale scores and menopause quality-of-life scores.
• Against hormones, on the Kupperman index (a menopause symptom score): five studies gave contradictory results.
• “Total effective rate” (an overall response rating): pooling 10 studies of the formula alone or 2 studies of the formula as an add-on, both improved the response rate compared with hormones.
• Mood and sleep: 3 studies found that the formula plus hormones lowered depression and anxiety scale scores and traditional symptom scores more than hormones alone; one study found an effect on an insomnia scale.
• Blood markers: 7 studies gave contradictory effects on laboratory measurements compared with hormones.
• Side effects: only 2 studies reported adverse effects; the others did not mention them.

The review contains a tension worth noticing. Using the GRADE system, the authors rated the quality of evidence for the primary outcomes as moderate to high. Yet their overall conclusion was that the findings “do not allow an assessment of the evidence because the low-quality studies included cannot be reproduced,” and that rigorous randomised trials are still needed. The reader is left with the authors’ own final verdict: the area is worth further research, and the existing trials cannot settle it.

The 2026 narrative review

The 2026 Phytomedicine review by Chen and colleagues, drawing on publications from 1965 to 2025, reports that the formula and its modified versions, often combined with hormone therapy, improve symptoms in menopausal syndrome, osteoporosis and premature ovarian failure, based on randomised trials involving thousands of patients. It is a narrative review rather than a graded systematic review, and its own conclusion calls for evidence-based clinical trials to move the formula “from empirical use to precision medicine.”

Menopause and blood pressure

A 2019 systematic review by Xiong and colleagues looked at Chinese herbal medicine in general for high blood pressure after menopause. It included 39 randomised trials with 3,823 participants. Pooled results favoured herbal medicine added to blood-pressure drugs over the drugs alone, for blood pressure, blood-pressure variability, menopausal symptoms, quality of life and hormone levels, and no severe adverse effects were identified. Er Xian Decoction was the most frequently prescribed formula in these trials. The authors concluded that the effectiveness and safety of the decoctions remain uncertain because of methodological shortcomings. This review covers many formulas together, so its pooled results are not results for Er Xian Decoction alone.

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Bone Density After Menopause

Bone is the second main use of the formula, and here the trials are more numerous but almost all are add-on studies run in China against calcium supplements or standard drugs, not against placebo. The separate Bone Density and Menopause article covers the 24-month trial of an Epimedium flavonoid blend, which is a different product from this formula.

The 2017 review: 8 trials, low quality

Li and colleagues in Beijing searched six databases up to September 2016 and found 8 randomised trials with 644 patients. The methodological quality of the trials was generally low.

• Two trials compared the formula with calcium tablets and found higher bone mineral density at the lumbar spine (mean difference 0.05) and at the greater trochanter of the hip (mean difference 0.06).
• Two trials compared the formula plus calcium tablets and calcitriol (active vitamin D) with calcium tablets and calcitriol alone, and found higher bone density at the femoral neck (mean difference 0.04, with a confidence interval running from 0.00 to 0.09) and changes in blood calcium and phosphorus.
• The adverse reactions reported were mainly slight gastrointestinal symptoms.

The authors described the result as suggestive evidence that the formula, alone or combined, outperformed basic supplements, but stated that “the evidence remains weak” and that larger randomised, double-blind, placebo-controlled trials were needed.

The 2026 review: 13 trials in 1,269 women

An updated review from Kyung Hee University in Seoul, published in the Journal of Clinical Densitometry in 2026, searched MEDLINE, Embase, CENTRAL, CNKI, Wanfang, SinoMed and VIP up to July 2025. It found 13 randomised trials with 1,269 women, all conducted in China and published between 2012 and 2025. The review assessed the formula combined with conventional treatments.

• Lumbar spine density: mean differences of 0.05 g/cm² when the formula was added to drug treatment and 0.09 g/cm² when it was added to calcium and vitamin D.
• Femoral neck density: a mean difference of 0.06 g/cm² in both settings.
• Pain: lower scores on a visual analogue pain scale, by 1.17 and 0.88 points in the two settings.
• Overall response: odds ratios of 3.62 and 3.56 in favour of the formula.
• Side effects: five studies reported adverse events; pooled analysis suggested fewer events with the formula (risk ratio 0.68), but this was statistically significant in only one trial.
• Fractures: only one study reported fracture incidence. It favoured the formula, but the result was not statistically significant.
• Consistency: results varied substantially between studies, and the variation shrank partly when trials at high risk of bias were removed.

The authors concluded that the formula combined with conventional therapy may improve bone density and reduce pain, that the safety evidence is insufficient for firm conclusions, and that the current evidence is limited to small, single-country trials with methodological limitations. Fractures — the outcome that bone-density treatment exists to prevent — have barely been measured. The site’s Osteoporosis section covers the treatments that have fracture data.

One small trial with exercise

A 2022 randomised trial combined the formula with Baduanjin, a traditional Chinese qigong exercise, in 50 women with postmenopausal osteoporosis split into three groups: formula alone (15 women), exercise alone (18) and both together (17), followed for 8 and 16 weeks. The combined group showed the strongest effects on bone density, balance tests and anxiety and depression scores. The authors described the study as confirming that a larger trial is feasible. With groups of 15 to 18 women and no placebo, it is a pilot study.

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Laboratory and Animal Findings

Most of the research on Er Xian Decoction is in rats, mice and cell cultures. These studies explain why researchers are interested in the formula. They do not show that it works in people, and doses given to rats per kilogram of body weight do not translate directly to human doses.

Bone in rats without ovaries

The standard animal model of menopause is the ovariectomised rat — a female rat whose ovaries have been removed, so that estrogen falls and bone is lost.

• 2006, Shanghai: in ovariectomised rats given the formula at 300 or 600 mg/kg daily for 12 weeks, the fall in bone density and the shrinking of the uterus were suppressed, as they were with a synthetic estrogen (nylestriol) given for comparison. The formula also corrected the drop in blood calcium, phosphorus and estradiol seen in the untreated rats, and bone strength in the treated rats was comparable to that of rats that had not had surgery.
• 2012, Shanghai: a study in ovariectomised rats compared the whole formula, Epimedium herb alone and purified icariin with estrogen. All three improved bone density and structure in the rats. The whole formula acted on both bone building and bone breakdown, as estrogen does, while Epimedium and icariin worked mainly by slowing bone breakdown. All three had fewer unwanted effects on the uterus, mammary gland and vagina than estrogen did, and the authors rated the whole formula as having the best efficacy and safety profile of the three in these rats.
• 2014, Hong Kong: in ovariectomised rats, the formula improved the internal structure and strength of the thigh and shin bones and did better than Epimedium or curculigo given alone. In bone-forming cells grown in the laboratory, the growth-promoting effect of the formula disappeared when an estrogen-blocking drug was added, which points to the estrogen receptor as part of the mechanism in cells.

Sweating and hormones in older rats

A 2016 Hong Kong study tested a modified formula, with schisandra fruit (Wu Wei Zi) added, in 12- to 14-month-old female rats used as a menopause model, at 5.5, 11 and 22 g/kg once daily for 6 weeks, with 10 animals per group. At 11 g/kg the modified formula reduced sweating measured on the rats’ foot pads after 3 and 6 weeks, raised blood estradiol, and lowered the pituitary hormones FSH (follicle-stimulating hormone) and LH (luteinising hormone).

That rat result sits uneasily beside the human trial. In rats, the modified formula raised estradiol; in the 2013 Hong Kong trial in women, blood hormone levels did not differ from placebo. The two studies used different versions of the formula in different species, and neither settles how the formula affects hot flushes in people.

Cooking the herbs together versus separately

A 2017 study compared the formula boiled as one pot with the six herbs boiled separately and then mixed. The separately prepared mixture contained about twice the amounts of four measured compounds (mangiferin, ferulic acid, jatrorrhizine and palmatine). In 12-month-old female rats, the separately prepared mixture was more effective at stimulating aromatase — the ovarian enzyme that makes estradiol — and at raising antioxidant enzymes in the liver. Whether the preparation method changes anything in people has not been tested, but the finding means that a product made from separately extracted herbs and the traditional pot-boiled decoction may not be chemically the same.

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Estrogen-Like Activity and Estrogen-Sensitive Tissues

Any treatment that acts on estrogen receptors raises the question of breast and uterine tissue. A 2021 study from the Hong Kong Polytechnic University addressed it directly, and its authors state the concern in their own words: the growing use of “kidney”-nourishing formulas such as Er Xian Decoction for menopausal symptoms and osteoporosis has raised concerns about their safety and about interactions with prescription drugs, since both act through estrogen receptors.

In rats

Ovariectomised rats were given the formula alone or combined with selective estrogen receptor modulators (SERMs) — drugs such as raloxifene, used for bone, and tamoxifen, used in breast cancer — for 12 weeks. The formula eased estrogen-deficiency changes in the rats’ bone and brain without producing estrogen-like effects in the breast or uterus. Statistical tests showed that the formula and the SERMs interacted, but the formula did not significantly change how bone, breast or brain responded to the drugs. In the uterus, the combination appeared to suppress the estrogen-like effect of raloxifene and tamoxifen.

In cells

Serum from treated rats was applied to human cell lines grown in the laboratory. It directly stimulated the growth or maturation of bone cells, nerve cells, MCF-7 breast cancer cells and Ishikawa endometrial (womb-lining) cancer cells, and it changed the effects of tamoxifen on bone cells and MCF-7 breast cancer cells in the dish.

The authors concluded that the formula acts in an estrogen-like way that is selective by tissue and that it interacts with SERMs. Two findings point in different directions: in whole rats, breast and uterus showed no estrogen-like response, while in isolated cells, breast and endometrial cancer cell lines were stimulated. The abstracts read for this page report no trial of the formula in women with a history of breast or endometrial cancer, or in women taking tamoxifen or raloxifene, so how these laboratory findings apply to those women is unknown. The research raises a concern for exactly those groups.

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Safety Findings and Liver-Injury Reports

What the trials of the formula report

• The 2013 Hong Kong placebo trial reported no serious adverse events over 12 weeks, with blood counts, kidney function and liver function in the normal range before and after treatment.
• The 2017 bone review reported that adverse reactions were mainly slight gastrointestinal symptoms.
• The 2019 menopause review found that only 2 of its 16 studies reported adverse effects at all; the rest did not mention them.
• The 2026 bone review concluded that the evidence on safety remains insufficient to draw firm conclusions.

In short, short trials of the formula have not shown a safety signal, but most of them did not report on safety carefully, and none of the trials read for this page followed women for years.

Liver injury and Epimedium

The liver concern comes from Epimedium itself, one of the formula’s six herbs, and from products that contain it. None of the liver-injury reports read for this page concerned Er Xian Decoction specifically.

• A hospital series in Beijing (2022): Peking University First Hospital reviewed 726 patients treated for drug-induced liver injury between January 1995 and August 2019. Chinese herbal medicine caused 353 of the cases (48.6%). The three herbs most often identified as the cause were Polygonum multiflorum (he shou wu, 38 cases), Fructus Psoraleae (35 cases) and Epimedium (26 cases). Liver enzymes and bilirubin were higher, and severe cases more common, in herbal cases than in cases caused by Western drugs, and the herbal cases had been taking the medicine for longer. The authors noted that the incidence of herbal liver injury was rising year by year.
• A Chinese safety review (2019): an analysis of ancient and modern literature reported that reports of adverse reactions to Epimedium and to Chinese patent medicines containing it had gradually increased. Comparing two such patent medicines, the authors listed hepatotoxicity among several types of toxicity they attributed to Epimedium, alongside cardiovascular toxicity and neurotoxicity. They also noted that the Chinese Pharmacopoeia accepts the leaves of several Epimedium species under one name, and that the species differ in composition and toxicity.
• A 2024 laboratory study opens with the statement that there have been numerous reports of adverse reactions to Epimedium in recent years and that the most common side effect is liver injury. Its network analysis and experiments in human liver cells identified icaritin, a breakdown product of Epimedium flavonoids, as a key potentially toxic component.
• A 2026 study reports that liver-injury reports linked to Epimedium taken together with Fructus Psoraleae, a commonly paired herb, have gradually increased in recent years.

How the injury may happen: animal and cell work

• In mice, icariside II, a main Epimedium compound, combined with a dose of bacterial toxin that does not harm the liver on its own, raised liver enzymes and caused liver inflammation. The authors describe this as an idiosyncratic pattern — injury that depends on the individual’s immune state rather than simply on dose (2020).
• In mice given a water extract of Epimedium at 6.5 or 19.5 g/kg a day for 14 weeks, the high dose caused cholestatic liver injury (a blockage of bile flow), which the authors describe as consistent with reported clinical cases (2022).
• A 2025 review describes Epimedium flavonoids as having both protective and toxic effects on the liver, with the toxic mechanisms less well understood but likely involving oxidative stress and pyroptosis, an inflammatory form of cell death.

The Safety, Adulteration and Product Quality article covers Epimedium’s other safety questions, and Liver Injury from Supplements describes the signs of herb-induced liver injury. Decisions about herbal formulas alongside other medicines belong with a clinician who knows the full list of what a person takes.

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What Is Not Known

• Whether the hot-flush result holds up. One 12-week placebo-controlled trial in 108 Hong Kong women is the only placebo comparison reported in the menopause review abstracts read for this page. No second placebo trial confirming it was found for this page.
• How it works in people. Rat studies point to estrogen-like activity, but in the human trial blood hormone levels did not differ from placebo.
• What dose and preparation were tested. Chemical content depends on the extraction method, and boiling the herbs together or separately changes the amounts of measured compounds. The trials are not directly comparable with each other, or with any given product.
• Whether it prevents fractures. Bone-density gains were reported in small add-on trials, all in China; only one trial reported fractures, and its result was not statistically significant.
• Long-term safety. No trial read for this page followed women for years, most trials did not report adverse effects, and the liver-injury reports for Epimedium come from hospital series and pharmacovigilance rather than from controlled studies of the formula.
• Effects in women with hormone-sensitive cancers or on SERM drugs. The only data are from rats and cell cultures, and they show interactions with tamoxifen and raloxifene.
• Whether the result belongs to Epimedium. Every finding on this page is for the six-herb formula, not for Epimedium alone, and every Epimedium-only finding elsewhere on the site is not a finding for the formula.

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Key Research Papers

1. Zhong LL, Tong Y, Tang GW, Zhang ZJ, Choi WK, Cheng KL, Sze SC, Wai K, Liu Q, Yu BX. A randomized, double-blind, controlled trial of a Chinese herbal formula (Er-Xian decoction) for menopausal symptoms in Hong Kong perimenopausal women. Menopause. 2013;20(7):767-76. PubMed PMID: 23793167
2. Wang Y, Lou XT, Shi YH, Tong Q, Zheng GQ. Erxian decoction, a Chinese herbal formula, for menopausal syndrome: An updated systematic review. J Ethnopharmacol. 2019;234:8-20. PubMed PMID: 30658181
3. Chen HY, Cho WC, Sze SC, Tong Y. Treatment of menopausal symptoms with Er-xian decoction: a systematic review. Am J Chin Med. 2008;36(2):233-44. PubMed PMID: 18457358
4. Chen GC, Hu SJ, Yan YY, Song ZL, Hu M, Liu TT, Zhang QL, Xu JL, Qin LP, Zhang QY. Er-xian Decoction: A comprehensive review on chemical constituents, quality control, pharmacokinetics, pharmacological properties and clinical applications. Phytomedicine. 2026;157:158298. PubMed PMID: 42184498
5. Li JJ, Li JT, Fu JP. Erxian tang--introduction of a Chinese herbal formula, clinical practice, and experimental studies. Chin J Integr Med. 2007;13(1):67-73. PubMed PMID: 17578324
6. Wang S, Tong Y, Ng TB, Lao L, Lam JK, Zhang KY, Zhang ZJ, Sze SC. Network pharmacological identification of active compounds and potential actions of Erxian decoction in alleviating menopause-related symptoms. Chin Med. 2015;10:19. PubMed PMID: 26191080
7. Xiong X, Yang X, Li X, Yue G, Xing Y, Cho WC. Efficacy and safety of Chinese herbal medicine for patients with postmenopausal hypertension: A systematic review and meta-analysis. Pharmacol Res. 2019;141:481-500. PubMed PMID: 30639372
8. Li JY, Jia YS, Chai LM, Mu XH, Ma S, Xu L, Wei X. Effects of Chinese herbal formula Erxian decoction for treating osteoporosis: a systematic review. Clin Interv Aging. 2017;12:45-53. PubMed PMID: 28115834
9. Pyun J, Hwang M, Yang T, Kwon S, Jung Y, Yeum C, Ko E, Cho SH. Erxian decoction for postmenopausal osteoporosis: An updated systematic review and meta-analysis. J Clin Densitom. 2026;29(3):101714. PubMed PMID: 42155162
10. Li K, Yu H, Lin X, Su Y, Gao L, Song M, Fan H, Krokosz D, Yang H, Lipowski M. The Effects of Er Xian Decoction Combined with Baduanjin Exercise on Bone Mineral Density, Lower Limb Balance Function, and Mental Health in Women with Postmenopausal Osteoporosis: A Randomized Controlled Trial. Evid Based Complement Alternat Med. 2022;2022:8602753. PubMed PMID: 35815264
11. Nian H, Qin LP, Zhang QY, Zheng HC, Yu Y, Huang BK. Antiosteoporotic activity of Er-Xian Decoction, a traditional Chinese herbal formula, in ovariectomized rats. J Ethnopharmacol. 2006;108(1):96-102. PubMed PMID: 16765003
12. Xue L, Wang Y, Jiang Y, Han T, Nie Y, Zhao L, Zhang Q, Qin L. Comparative effects of er-xian decoction, epimedium herbs, and icariin with estrogen on bone and reproductive tissue in ovariectomized rats. Evid Based Complement Alternat Med. 2012;2012:241416. PubMed PMID: 23227099
13. Wong KC, Lee KS, Luk HK, Wan HY, Ho CK, Zhang Y, Wong MS. Er-xian Decoction exerts estrogen-like osteoprotective effects in vivo and in vitro. Am J Chin Med. 2014;42(2):409-26. PubMed PMID: 24707871
14. Wang SW, Wu FH, Zhang YB, Zhang L, Su J, Wong HK, Liu AH, Cheung HP, Ng TB, Tong Y, Sze SC. Ameliorating effect of Erxian decoction combined with Fructus Schisandrae chinensis (Wu Wei Zi) on menopausal sweating and serum hormone profiles in a rat model. Chin Med. 2016;11:47. PubMed PMID: 27895702
15. Cheung HP, Wang SW, Ng TB, Zhang YB, Lao LX, Zhang ZJ, Tong Y, Chung FW, Sze SC. Comparison of chemical profiles and effectiveness between Erxian decoction and mixtures of decoctions of its individual herbs: a novel approach for identification of the standard chemicals. Chin Med. 2017;12:1. PubMed PMID: 28053654
16. Wong KY, Zhou L, Yu W, Poon CC, Xiao H, Chan CO, Mok DK, Wong MS. Water extract of Er-xian decoction selectively exerts estrogenic activities and interacts with SERMs in estrogen-sensitive tissues. J Ethnopharmacol. 2021;275:114096. PubMed PMID: 33823166
17. Tan K, Yang W, Pang L, Hou F. Differences in clinical characteristics among 726 patients with Chinese herbal medicine- or Western medicine-induced liver injury. Medicine (Baltimore). 2022;101(32):e29909. PubMed PMID: 35960048
18. Wang D, Jia DX, Li ZZ, Niu MY, Xie WC, Wang XK, Gao XM, Wang JX. [Discussion on safety evaluation and risk control measures of Epimedii Folium]. Zhongguo Zhong Yao Za Zhi. 2019;44(8):1715-1723. (Article in Chinese.) PubMed PMID: 31090340
19. Wang J, Cao Y, Sun M, Zhang T, Yu G, Xu H, Li T, Zhang C, Sun Y. Integrating metabolomics and bioinformatics to reveal the mechanism of Epimedium-induced liver injury. Biomed Chromatogr. 2024;38(9):e5948. PubMed PMID: 38981997
20. Shi W, Li H, Liu T, Hlbiyat U, Yang J, Liu Z, Gao Y, Bai Z, Xiao X. Novel strategies for identification and prevention of idiosyncratic liver injury caused by TCM compatibility: Exemplification by Epimedii Folium and Psoraleae Fructus. Phytomedicine. 2026;153:157841. PubMed PMID: 41655541
21. Wang Z, Xu G, Wang H, Zhan X, Gao Y, Chen N, Li R, Song X, Guo Y, Yang R, Niu M, Wang J, Liu Y, Xiao X, Bai Z. Icariside Ⅱ, a main compound in Epimedii Folium, induces idiosyncratic hepatotoxicity by enhancing NLRP3 inflammasome activation. Acta Pharm Sin B. 2020;10(9):1619-1633. PubMed PMID: 33088683
22. Zhao JQ, Zhao Z, Zhang C, Sun JX, Liu FJ, Yu T, Jiang Y, Li HJ. Long-term oral administration of Epimedii Folium induced cholestasis in mice by interfering with bile acid transport. J Ethnopharmacol. 2022;293:115254. PubMed PMID: 35381309
23. Yue M, Liu Y, Feng X, Cao B, Fei X, Li G, Li C. Epimedii Folium flavonoids: A double-edged sword effect on the liver, a dual exploration of efficacy and toxicity. J Pharm Anal. 2025;15(10):101269. PubMed PMID: 41208921

PubMed Topic Searches

1. PubMed: Er Xian Decoction and menopause
2. PubMed: Er Xian Decoction and osteoporosis trials
3. PubMed: Er Xian Decoction and estrogen activity
4. PubMed: Epimedium and liver injury

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Connections

• Epimedium (Horny Goat Weed) Benefits — the hub for these articles
• Epimedium (Horny Goat Weed) — the main herb page
• Traditional Use in Chinese Medicine — the formula’s place in Chinese medical theory
• Bone Density and Menopause — the 24-month trial of an Epimedium flavonoid blend
• Safety, Adulteration and Product Quality — Epimedium’s other safety questions
• Dong Quai and Menopause: An Evidence Review — one of the formula’s six herbs, studied on its own
• Hot Flashes and Night Sweats — the symptom the placebo trial measured
• Black Cohosh for Menopause and Hot Flashes — another herbal option with its own trial record
• Osteoporosis — treatments with fracture data
• Liver Injury from Supplements — herb-induced liver injury in general
• He Shou Wu Liver Health and Hepatotoxicity Warning — the herb named most often in the Beijing liver-injury series

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