Progestogens for endometriosis: forward to the past.

We performed a MEDLINE and EMBASE search to identify all studies published in the last decade in the English language literature on the use of progestogens for the treatment of endometriosis. Our aim was to clarify the biological rationale for treatment and define the drugs that can be used with their doses, routes of administration, efficacy and tolerability. Progestogens may prevent implantation and growth of regurgitated endometrium inhibiting expression of matrix metalloproteinases and angiogenesis, and they have several anti-inflammatory in-vitro and in-vivo effects that may reduce the inflammatory state generated by the metabolic activity of the ectopic endometrium, and the consequent immune response. Oral contraceptives increase the abnormally low apoptotic activity of the endometrium of women with endometriosis. Moreover, anovulation, decidualization, amenorrhoea and the establishment of a steady estrogen-progestogen milieu contribute to disease quiescence. Progestogens are effective in the control of pain symptoms in approximately three out of four women with endometriosis. Their effect does not seem to be inferior to that of other drugs used for the disease. Different compounds can be administered by the oral, intramuscular, subcutaneous, intravaginal or intrauterine route, each with specific advantages or disadvantages. Medical treatment plays a role in the therapeutic strategy when administered over a prolonged period of time. Given their good tolerability, minor metabolic effects and low cost, progestogens must therefore be considered drugs of choice and are currently the only safe and economic alternative to surgery. However, their contraceptive effectiveness limits their use to women who do not wish to have children in the short term.