Improvements of Vaginal Atrophy without Systemic Side Effects after Topical Application of Pueraria mirifica, a Phytoestrogen-rich Herb, in Postmenopausal Cynomolgus Macaques

The estrogenic efficacy of topical vaginal application of Pueraria mirifica extract (PM) on the restoration of vaginal atrophy. Topical vaginal treatment with PM stimulated the maturation of the vaginal epithelium without causing systemic side effects in postmenopausal monkeys. The implication is that PM could be a safer alternative to treat vaginal atrophy in postmenopausal women.

Together with vaginal atrophy, a decrease in vaginal secretion and increase in vaginal pH also occurs, which leads to an increased incidence of vaginitis, vaginal dryness, itching, burning and irritation . Most vaginal atrophic patients complain of dyspareunia during sexual intercourse. Conjugated equine estrogens (CEE) cream, which contained a mixture of estrone, equilin, 17β-dihydroequilin,17α-estradiol and 17α-dihydroequilin at 0.625 mg/g cream, is currently the most common choice of vaginal product for the treatment of vaginal atrophy. However, the reported side effects of CEE cream include an increased occurrence of endometrial hyperplasia, endometrial stimulation, breast tenderness and uterine bleeding . Therefore, the use of synthetic phytoestrogens or an extract of phytoestrogen containing plants for the treatment of vaginal atrophy has become attractive as a potentially safer alternative . Pueraria mirifica (PM) is an endemic herb of Thailand, and its tuberous root contains a high amount of phytoestrogens.

If daily topical application of a vaginal cream containing PM extract showed a similar efficacy to that of CEE cream using vaginal tissue proliferation and the vaginal pH as markers, (ii) if vaginally administered PM and CEE creams could be absorbed through the vaginal mucosa into the blood circulation and have a systemic side effect using the decrease in plasma luteinizing hormone (LH) as an indicator and (iii) if changes in sex skin reddening in postmenopausal cynomolgus macaques can reflect the systemic effects of vaginal application of CEE and PM.

Preparation of PM extract and phytoestrogen analysis

The PM cultivar SARDI 190, from Kasetsart University, Kampangsan campus (lot no. 0070317), was used as the source material. Tuberous roots of 3-year-old plants were harvested in March 2007.

Together with the increased proportion of vaginal superficial cells, treatment with the PM extract also resulted in a decrease in vaginal pH to a slightly acidic level similar to that observed in the CEE-treated group. Indeed, estrogens and phytoestrogens stimulate vaginal epithelial maturation and subsequent glycogen production. Glycogen-consuming Lactobacilli can then colonize the vagina and lower the vaginal pH by catabolism of glycogen into lactic acid.

A 28-day topical vaginal treatment with PM extract could stimulate maturation of the vaginal epithelium and lead to an acidic vaginal pH in cynomolgus macaques at least 5 years postmenopause. By using topical vaginal application, PM did not induce any discernible systemic side effects, as indicated by the absence of detected changes in the plasma LH levels and sex skin coloration. With respect to previous findings in postmenopausal women, the oral consumption of PM was reported to also ameliorate other postmenopausal symptoms, such as hot flushes, frustration, sleep disorder, skin dryness, high blood cholesterol levels and dyspareunia. In addition, oral administration of PM also maintained the bone mass in ovariectomized rats and had beneficial cardiovascular effects in ovariectomized rabbits . Taken together, these results suggest that PM should be a safer alternative choice for treatment of vaginal atrophy in postmenopausal women.

In conclusion, these results clearly demonstrate that topical vaginal treatment with PM plays a key role in the maturation of the vaginal epithelium in postmenopausal monkeys. Additionally, PM should be applicable to treatment of vaginal atrophy and reduce the incidence of related symptoms in menopausal women.

Received: December 26, 2013

Accepted: March 15, 2014

Published online in J-STAGE: April 21, 2014

©2014 by the Society for Reproduction and Development

Correspondence: S Jaroenporn (e-mail: [email protected] or [email protected])

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NCBI website: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085389/