Changing concepts of medical treatment of endometriosis

Abstract

Studies on the natural history of endometriosis have demonstrated that the majority of endometriosis implants tend to progress, a finding that indicates eradication of the lesions by medical and/or surgical approaches. Infertility and dysmenorrhea are other indications for medical therapy in this disease. In recent prospective and controlled studies, progestin (at high doses), gestrinone and GnRH agonist analogues have been equally effective as regards elimination of endometriosis and relief of endometriosis-associated symptoms, compared to danazol, a standard treatment in endometriosis. These four classes of drugs differ, however, in their adverse effects and as regards compliance. Danazol is a steroid with androgenic and anabolic effects and it adversely affects lipid metabolism. Gestrinone and 17-OH progestins are weaker, and GnRH agonist analogues and some progestins neutral in these respects. GnRH agonist analogues induce a hypo-estrogenic state with associated climacteric symptoms and mineral loss from the bones. The clinical value of combinations of GnRH analogue and steroid(s), used to prevent these side-effects, is so far unclear. Laparoscopic microsurgery has revolutionized the treatment of endometriosis lesions. Hence, hormone treatment as a supplement to microsurgical approaches may become a dominant form of medical therapy in endometriosis. The definitive value of pre- or post-operative hormonal treatment in this disease should, however, be tested in controlled trials. Such studies have proved antiprostaglandins to be useful in the treatment of dysmenorrhea secondary to endometriosis. Because each of the four drugs was ineffective in the treatment of infertility associated with endometriosis it is a waste of time to expose patients desiring pregnancy to long-term hormonal therapy. Ovarian hyperstimulation with IVF and other methods of assisted fertilisation are promising alternatives, but their definitive value is so far unproven in this disease. Conclusively, the significance of medical therapy in endometriosis is only partly resolved, and therefore, many therapeutic problems await prospective randomised trials and new innovations.

Reappraisal of progestins in endometriosis therapy

“…Other methods are complementary. The observations showing that suppressive endocrine treatment does not improve the prospects of infertile endometriosis patients have further diminished the significance and use of such therapy (3,6). Recent data showing that laparoscopic elimination of minimal or mild endometriosis enhances fecundity of infertile women (12) is in line with this trend.…”

“…During the past decade, different GnRH agonist analogues have completed the list of drugs inducing antiproliferative effects on endometriosis tissue. Comparisons with danazol have repeatedly failed to reveal any significant difference in their ability to abolish endometriosis implants or to alleviate pelvic pain and other subjective symptoms of endometriosis (3). It is also significant that MPA at doses up to 100 mg a day induces less harmful changes in lipid and lipoprotein metabolism than androgenic danazol.…”

“…The 40-year history of conservative medical therapy of endometriosis demonstrates that many substances and their combinations have been tested, including low-dose oral contraceptives, progestin alone (several candidates), danazol, gestrinone and gonadotrophin-releasing hormone (GnRH) agonist analogues (2,3). Unfortunately, the clinical efficacy of different treatment modalities was investigated mostly retrospectively or in uncontrolled trials until the late 1980s (2,3). The more recent studies on the efficacy of drug therapy have been prospective and based on adequate study designs with control therapy and endoscopic confirmation of endometriosis and its behaviour.…”

Dominant Expression of Progesterone Receptor Form B mRNA in Ovarian Endometriosis

“…The hormonal responsiveness of endometriosis is evidenced by growth stimulation with steroid hormone, regression with surgical castration, and growth-suppressive effects of danazol, medroxyprogesterone acetate [1], and gonadotropin-releasing hormone analogs [2]. In addition, the implicated presence of sex steroid receptors is consistent with the steroidal growth of endometriosis [3, 4], and PR mRNA is present in ectopic endometriotic endometrium [5]as well as in normal uterine endometrium.…”

Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats

“…For the control of adverse effects due to hypoestrogenism induced by GnRH-a, combination therapy with GnRH-a and a gestagen (e.g. MPA) has been proposed for the treatment of endometriosis (25). Because dienogest has progestational activity and no effect on BMD, we also evaluated the effect of a combination of dienogest with buserelin on experimental endometriosis.…”