Protective effect of dienogest on chemotherapy-induced reduced fertility in female rats

Hideaki Tsuyoshi, Makoto Orisaka, Shin Fukuda, Katsushige Hattori, Benjamin K. Tsang, Yoshio Yoshida
Steroids · 2014 · vol. 93 , pp. 1–7 · doi:10.1016/j.steroids.2014.10.010 · PMID:25449767 · W2012660781
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Dienogest administration protected female rats from chemotherapy-induced ovarian damage and subsequent reduced fertility by preserving ovarian follicle numbers and reducing apoptosis.

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Abstract

Reduced fertility is one of the main long-term consequences of chemotherapy given for lymphoma, leukemia, and other malignancies in young women. We examined with a female rat model whether and how dienogest, a fourth-generation progestin, modulates reduced fertility following exposure to gonadotoxic chemotherapy. Female rats were administered cyclophosphamide with or without GnRH agonist and different concentrations of dienogest for 20 days. Animals were sacrificed on Day 29, and the numbers of follicle at primordial, preantral and antral stage in the ovaries were counted histologically. Rats treated with sterile saline solution (as control), cyclophosphamide, cyclophosphamide plus GnRH agonist, and cyclophosphamide plus dienogest were also mated with male rats to evaluate their fertility and pregnancy outcomes. Cyclophosphamide significantly reduced the number of primordial follicles, whereas dienogest suppressed depletion of primordial follicle pool induced by chemotherapy. Although the rats exposed to cyclophosphamide alone failed to deliver live births, co-treatment with dienogest improved the pregnancy outcomes of treated rats. The protective effect of dienogest on chemotherapy-induced ovarian damage and reduced fertility was comparable to that of GnRH agonist. The present results suggest that the co-administration of dienogest and chemotherapy may be a useful strategy in preserving ovarian function and fertility in premenopausal women facing gonadotoxic chemotherapy.

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MeSH descriptors

Antineoplastic Agents, Alkylating Cyclophosphamide Fertility Agents Infertility, Female Nandrolone Animals Antineoplastic Agents, Alkylating Cyclophosphamide Drug Evaluation, Preclinical Female Fertility Agents Fertility Agents Gonadotropin-Releasing Hormone Gonadotropin-Releasing Hormone Infertility, Female Infertility, Female Male Nandrolone Nandrolone Nandrolone

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