Cosima Brucker, M.D.
Professor, Section Head, Section for Gynaecologic Endocrinology and Reproductive Medicine, Attending Physician, University Women's Hospital, Ulm, Germany

A randomized, multicenter trial comparing a once-monthly combined injectable contraceptive to an oral contraceptive has been completed in Europe. The injectable, to be marketed under the name Lune or Lunella, is a combination of medroxyprogesterone (MPA) and ethinyl cypionate (E₂C). The contraceptive is administered to the anterior thigh, deltoid, or gluteus maximus muscle every 28 to 30 days not to exceed an interval of 33 days. The analysis of the controlled trial demonstrates a very high rate of efficacy, safety, and patient satisfaction. The results of the European trial are comparable to a previous trial conducted in the U.S., where MPA/E₂C has already been licensed for use by the Food and Drug Administration. In both trials, more than 85% of women were satisfied or very satisfied with this form of contraception. Results of the European study are also consistent with clinical trials conducted by the World Health Organization. In those studies, more than 7000 women were evaluated on this form of contraception over at least one year. All of the clinical trials indicate that MPA/E₂C offers a degree of protection against pregnancy that is comparable with surgical sterilization. There are no serious adverse events, and the majority of women achieve one predictable withdrawal bleed per treatment cycle. The combined injectable is expected to significantly expand contraceptive options, offering a highly effective option independent of once daily compliance

Lee Shulman, MD
Professor, Departments of Obstetrics and Gynecology and Molecular Genetics Deputy Head, Department of Obstetrics and Gynecology, Directory, Division of Reproductive Genetics, University of Illinois at Chicago, Chicago, Illinois

A multicenter U.S. trial of 1,103 women comparing 5 mg estradiol cypionate/25mg medroxyprogesterone acetate (Lunella), a once-monthly injectable combination hormone contraceptive, to a combination oral contraceptive has shown that the monthly injectable demonstrates comparable contraceptive efficacy and safety as low dose oral contraceptives. The trial is one of the largest direct comparisons of these two forms of contraception ever undertaken). The safety and efficacy findings of the monthly injectable are encouraging in view of its potential advantages, including considerable compliance benefits and a more physiological dosing of sex hormones. This monthly injectable, which contains estradiol cypionate and medroxyprogesterone acetate, may also have a more favorable effect on lipid metabolism than other currently available hormone contraceptives. Coupled with other phase III trial evidence that the high degree of contraceptive efficacy associated with Lunelle is associated with high patient acceptance and rapid return to fertility after discontinuation, the U.S. trial data are consistent with the conclusion that this monthly injectable method will be a mainstream, first-start method amenable for use by the vast majority of women.

Background: To review the innate and adaptive immune systems and their roles in the establishment and progression of endometriotic lesions and to discuss the rationale for anti-inflammatory medications as approaches treatment.

Methods: Case-control clinical studies and laboratory- based in vitro analyses of primary cell cultures derived from normal human endometrium and ovarian endometriotic implants.

Results: Several cytokines, chemokines and growth factors (including vascular growth factors) are found in increased numbers in women with endometriosis. These appear to allow the peritoneal attachment and establishment of endometriotic lesions, which themselves become inflammatory foci. Defective immunosurveilance in women destined to develop endometriosis also may allow for the survival of ectopic endometrial tissue. Endometriotic stromal cells do not express the nonclassical HLA-G protein, however, resistance to apoptosis may be mediated through the secretion of FasL proteins which could impair phagocytotic function of Fas-bearing immune cells. Chronic progestin treatment of cells in vitro mitigates expression of a chemokine gene, and this treatment also reduces symptoms of inflammation in clinical trials.

Conclusions: A complex network of locally produced cytokines protect the survival and promote the inflammatory behavior of ectopic endometrial implants. Chemokines and other proinflammatory proteins secreted by endometriotic lesions recruit and activate peritoneal immune cells that contribute to the enhanced inflammatory reaction associated with endometriosis. Long-term progestins may be of therapeutic benefit as anti-inflammatory agents.