HERBS WITH OESTROGENIC (Estrogenic) ACTIVITY

The following is from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360864/

It lists 3 herbs – Yin Yang Huo (Xian Ling Pi), Dang Gui and Ren Shen (Ginseng).

Epimedium (Herba epimedii, Yin Yang Huo 淫羊藿)

Epimedium is classified as a ‘kidney-yang tonifying’ herb that is frequently used to treat disorders such as impotence, premature ejaculation and infertility, in combination with other herbs. Various preclinical studies have found that epimedium extract or its specific constituents (e.g. icaritin and icariside) have a selective oestrogen receptor modulator effect on breast cancer and uterine growth in nude mice.() Icariin, the major compound in epimedium, promotes oestrogen biosynthesis in human ovarian granulosa cells through aromatase, which converts androgens to oestrogens.() Another animal study found that icariin could exert anabolic effects on bone by activating oestrogen receptors (ER) and prevent ovariectomy-induced bone loss without inducing uterotrophic effects.()

These oestrogenic activities led to clinical studies using epimedium for menopausal symptoms. A randomised, placebo-controlled trial on 90 postmenopausal women, who consumed either 300 mL of aqueous herb extract or water daily for six months, reported significantly increased serum levels of oestradiol in the herbal group compared to the group that consumed only water. However, no recurrence of menstruation was reported in any of the subjects.() Another clinical trial on 50 late postmenopausal women, who were randomised to take either herb-derived phyto-oestrogen flavonoids (60 mg icariin, 15 mg genistein and 3 mg daidzein) or a placebo daily for 24 months, reported no significant increase in the treatment group’s serum oestradiol level. Interestingly, as with animal data, bone mineral density was maintained in the treatment group but was significantly reduced in the placebo group, without a concurrent hyperplasia effect on endometrium thickness.()

Ginseng (Radix Panax ginseng, Ren Shen 人参)

Ginseng is capable of restoring the oestrus cycle, interfering with the atrophy of reproductive target tissues caused by ovariectomy. These oestrogenic effects may be mediated by stimulating the biosynthesis of oestrogen in circulation and increasing the quantity of ER in the target organs.() It has also been suggested that the structural similarity between ginsenosides and oestradiol could be a contributing factor to the oestrogenic activity of ginseng.() An animal study reported the oestrogenic activity of ginseng on reproductive tissues in ovariectomised mice.() In a case report, a 12-year-old Korean-Japanese boy was diagnosed with gynaecomastia after taking 500 mg/day of red ginseng extract for one month for its strengthening effect; the gynaecomastia resolved upon cessation of the ginseng supplement. However, the boy’s oestradiol and testosterone levels were within normal levels.() A small number of case reports also showed an association between ginseng and postmenopausal vaginal bleeding and mastalgia. However, the exact source and ingredients consumed by the case subjects were not specified in these reports.(,)

In a placebo-controlled, double-blind clinical trial conducted in 72 postmenopausal women who were randomised to take either 3 g of red ginseng (including ginsenosides 60 mg/day) or a placebo daily for 12 weeks, no significant difference in serum oestradiol level was found between the treatment and placebo groups. However, subjects in the treatment group showed a significant improvement in menopausal symptoms, total cholesterol and low-density lipoprotein.()

Chinese angelica (Radix Angelicae sinensis, Dang Gui 当归)

Chinese angelica is a ‘blood-nourishing’ herb often used in gynaecological conditions such as perimenopausal syndrome and menstrual disorders. Chinese angelica extract or its constituent, ferulic acid, exhibits oestrogenic activity via various mechanisms: it stimulates the growth of both ER-positive and ER-negative breast cancer cells in vitro; competitively inhibits binding of oestradiol to ER in vitro; induces transcription activity in oestrogen-responsive cells in vitro; suppresses luteinising hormone (LH) secretion; and influences uterine growth and vaginal cytology in ovariectomised rats.(,) Its oestrogenic activity in humans is implicated by a case report of a 35-year-old man who developed gynaecomastia after ingesting ‘Dong Quai’ pills daily for a month (specific dosage unknown). His hormonal results (oestradiol, testosterone, follicle-stimulating hormone and LH levels) were all within normal range. His gynaecomastia regressed completely three months after he discontinued the pills.() However, this oestrogenic activity was not demonstrated in a double-blind, randomised, placebo-controlled trial in which 71 postmenopausal women were randomised to take either 4.5 g Chinese angelica or a placebo daily for 24 weeks. The study showed that the herb did not significantly increase the serum oestradiol level compared with the placebo, nor did it promote endometrial proliferation or increase the maturation of vaginal epithelial cells.()

Table I summarises the aforementioned herbs, the steroidal compounds identified in these herbs, and the highest level of evidence supporting or refuting their steroidal activities.