Reviewed: Chung D-J, Kim H-Y, Park K-H, et al. Black cohosh and St. John's wort (GYNO-plus_®) for climacteric symptoms. Yonsei Med J. 2007;48(2):289-294.

The Heart and Estrogen/Progestin Replacement Study and others have concluded that hormone replacement therapy (HRT) is effective for climacteric (menopausal) symptoms, but HRT also has serious side effects such as an increased risk of breast cancer and cardiovascular disease. Hence, many women choose to use alternative treatments such as black cohosh (Actaea racemosa syn. Cimicifuga racemosa, Ranunculaceae). Many climacteric symptoms have psychological components, and St. John's wort (Hypericum perforatum, Clusiaceae) is used to treat mild to moderate depression. The authors hypothesized that a fixed combination of black cohosh and St. John's wort may be more effective than monotherapy.

Korean peri- or post-menopausal women (n = 89; 77 completed the study) with typical climacteric symptoms, intact uteruses, and abstention from HRT for 3 months participated in this double-blind, placebo-controlled, multicenter study in Seoul, Korea. Patients received either Gyno-plus_® (n = 42; Jin-Yang Pharm, Seoul, Korea) or placebo (n = 35) for 12 weeks. Gyno-plus (264 mg tablet) contains 0.0364 mL black cohosh extract (equivalent to 1 mg terpene glycosides) and 84 mg St. John's wort dried extract (equivalent to 0.25 mg hypericin with 80% methanol). Climacteric complaints were evaluated with the Kupperman Index. In addition, vaginal maturation (to measure vaginal atrophy), serum hormone levels, cholesterol, and triglycerides were evaluated.

The mean Kupperman Index scores at 4 and 12 weeks were significantly lower in the Gyno-plus group than in the placebo group (P ≤ 0.002). At study end, the average decrease in Kupperman Index was 20.1 points in the Gyno-plus group and 8.2 points in the placebo group (P < 0.001). Vaginal dryness and reduced libido did not significantly improve. The mean hot flash score was significantly lower in Gyno-plus treated patients. There was no significant difference in vaginal atrophy, hormone profiles, total cholesterol, low density lipoprotein (LDL) cholesterol, or triglyceride levels between groups post-treatment. High density lipoprotein (HDL) cholesterol decreased in placebo-treated patients and increased in Gyno-plus-treated patients. The most common adverse event was gastrointestinal complaints (treatment group 12.85%; placebo 9.5%).

The authors conclude that the combination of black cohosh and St. John's wort in Gyno-plus was effective at improving typical climacteric symptoms in Korean peri- and post-menopausal women. The authors point out that efficacy can vary among different preparations. It is interesting that the authors hypothesized that the combination would be better than monotherapy but did not test this hypothesis by having a group of women taking only black cohosh. The manufacturer of Gyno-plus funded the study, which may explain why they did not include the monotherapy group. Hence, this study succeeds in demonstrating product efficacy, but it does not establish that the combination product is more efficacious than black cohosh monotherapy. However, efficacy of a combination product over monotherapy was shown recently in a large-scale (n= 6141), controlled, observational study over 6 months using an isopropanolic black cohosh extract (iCR, Remifemin; Schaper & Brmmer GmbH & Co KG, Salzgitter, Germany) or the herbal combination of iCR + St. John's wort (Remifemin plus).¹ By using the Menopause Rating Scale (MRS), the herbal combination (n= 3114 patients) was more effective in menopausal patients with pronounced mood complaints (MRS subscore Psyche: depressive moods, nervousness, irritability) compared to the black cohosh monotherapy (n= 3027).