Trials for development of once-a-month injectable, hormonal male contraceptive using dienogest plus testosterone undecanoate: dose standardization, efficacy and reversibility studies in rats.

Full Abstract

BACKGROUND: The study was conducted to test the potential of using dienogest (DNG) plus testosterone undecanoate (TU) in rats for development of a once-a-month injectable male hormonal contraceptive. STUDY DESIGN: Dose selection studies were initiated with administration of DNG in three different doses of 20, 30 and 40 mg/kg body weight (bw) per week plus TU 25 mg/kg bw once in every 6 weeks. Status of spermatogenesis and sperm count in epididymis was evaluated. The frequency of DNG intervention was later extended to every 2- and 4-week intervals. Mating studies, toxicity and reversibility of spermatogenesis following stoppage of treatment were carried out with DNG 40 mg/kg bw at 4-week intervals. RESULTS: Complete arrest of spermatogenesis was observed after 60 days of treatment at all doses of DNG (20, 30 and 40 mg/kg bw per week)+TU. However, weights of testis and accessory sex organs (epididymis, prostate and seminal vesicle) declined significantly 60 days post treatment compared to vehicle-treated controls. Epididymis in the treated animals was completely devoid of sperm. When the frequency of DNG injection (20 mg/kg bw) was extended to once every 15 days, a few immotile and decapitated sperm were observed in the epididymis. With TU treatment unchanged, animals receiving DNG (40 mg/kg bw) once either every 2- or 4-week intervals demonstrated good and uniform arrest of spermatogenesis. DNG 40 mg/kg per 4 weeks+TU also demonstrated a significant rise in germ cell apoptosis in the seminiferous epithelium. There was no significant increase in the serum high-density lipoprotein and low-density lipoprotein levels at the end of 120 days of treatment. Following withdrawal of treatment after 60 or 120 days, qualitative restoration of spermatogenesis was rapid in the former compared to the latter. CONCLUSION: Dienogest plus TU has the potential for development as a monthly injectable showing reversible hormonal male contraception with good efficacy.

Author information

Author/s: Misro, Man M (MM); Chaki, Shankar P (SP); Kaushik, Mahesh C (MC); Nandan, Deoki (D);

Affiliation: Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, New Delhi, India. mm_misro(-atsign-)yahoo.com

Journal and publication information

Publication Type: Journal Article

Journal: Contraception (Contraception), published in United States. (Language: eng)

Reference: 2009-Jun; vol 79 (issue 6) : pp 488-97

Dates: Created 2009/05/15; Completed 2009/08/19;

PMID: 19442786, status: MEDLINE (last retrieval date: 8/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Apoptosis - drug effects; physiology
Blood Chemical Analysis
Contraception - methods
Contraceptive Agents, Male - administration & dosage
Epididymis - drug effects; enzymology; metabolism
Female
Histocytochemistry
In Situ Nick-End Labeling
Injections, Intravenous
Litter Size

Litter Size
Male
Nandrolone - administration & dosage; analogs & derivatives
Pregnancy
Rats
Rats, Wistar
Sperm Count
Spermatogenesis - drug effects
Testis - drug effects; metabolism
Testosterone - administration & dosage; analogs & derivatives
alpha-Glucosidases - metabolism

Associated Chemicals: Contraceptive Agents, Male (0) ; Nandrolone (434-22-0) ; Testosterone (58-22-0) ; testosterone undecanoate (5949-44-0) ; dienogest (65928-58-7) ; alpha-Glucosidases (EC 3.2.1.20)

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