The Current Place of Progestins in the Treatment of Endometriosis

Karl-Werner Schweppe

Disclosures

Expert Rev of Obstet Gynecol. 2012;7(2):141-148. 

In This Article

Abstract and Introduction

Abstract

Endometriosis is a chronic disease that has a variety of symptoms and reduces quality of life in affected women. The patient complaints require surgical treatment, medical treatment, or both. Often long-term or repeated medication is necessary. Therefore, not only the efficacy, but also the tolerability and costs of a drug are relevant. Oral progestins with or without an estrogen component have been described as being effective in the treatment of endometriosis. A number of different substances have been tried; derivatives of natural progesterone or of C17-OH-progesterone, or derivatives of C19-nortestosterone. Their common characteristic is the secretory transformation of estrogen-primed uterine endometrium for which different doses are necessary because of the different biological activities of these derivatives. They differ with respect to their profile and potency of action on the hypothalamic–pituitary axis, metabolic processes, breast tissue and genital organs. They are similarly effective in the treatment of endometriosis-related complaints if sufficient doses are administered. Different routes of application (depot injections of medroxyprogesterone acetate, intrauterine release of levonorgestrel and subcutaneous implants of medroxyprogesterone acetate) are reported, with similar effects on symptoms. No effects are seen on reduced fertility in endometriotic patients and the data are inconsistent concerning direct effects on endometriotic cells in humans. Effects have been shown on proliferation and inflammatory reactions of endometrial stromal cells both in vitro and in vivo.

Introduction

For over 40 years, oral progestins lacking an estrogen component have been demonstrated to be effective in the treatment of endometriosis. Different derivatives of the progesterone (medroxyprogesteron acetate [MPA] and dydrogesterone) or derivatives of C19-nortestosterone (norethisterone, lynestrenol, desogestrel and dienogest, for example) have been used in treatment. They differ with respect to their profile and potency of action on the hypothalamic–pituitary axis, metabolic processes, breast tissue and genital organs. Secretory transformation of estrogen-primed uterine endometrium is their common characteristic, but the doses required to achieve this differ amongst the different derivatives. Progestins reduce the frequency and increase the amplitude of pulsatile gonadotropin-releasing hormone (GnRH) release, resulting in a reduction in follicle-stimulating hormone and luteinizing hormone secretion. Therefore, their continuous application leads to a suppression of ovarian steroidogenesis with anovulation and low serum levels of ovarian steroids. The hypoestrogenic and hypergestagenic status causes decidual transformation of the eutopic endometrium, and to some degree, in ectopic lesions too. In order to induce decidual transformation with resultant necrosis and resorption of the implant, however, concomitant estrogen action is required.[1] As continuous progestin therapy results in low serum estradiol levels, breakthrough bleeding is a common occurence.

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