Barbara Boughton

May 17, 2012

May 17, 2012 (San Diego, California) — A 1-year randomized study of postmenopausal women who took the new oral selective estrogen-receptor modulator (SERM) ospemifene (Ophena, Shionogi) for vulvovaginal atrophy suggests that the medication has no detrimental effects on the endometrium, according to researchers here the American Congress of Obstetricians and Gynecologists 60th Annual Clinical Meeting.

Shionogi filed a New Drug Application with the US Food and Drug Administration for the ospemifene 60 mg oral tablet as treatment for vulvovaginal atrophy in late April.

Phase 3 clinical trial results on the use of ospemifene 60 mg have revealed that treatment improves the symptoms of dyspareunia and vaginal dryness and decreases vaginal pH in postmenopausal women.

Although this long-term study of 140 postmenopausal women is unlikely to be the last word on the safety of ospemifene, it does provide initial information on the impact of this medication on the endometrium, the researchers report.

"Our study results indicate that only 2% of patients showed any degree of endometrial proliferation, and there were no cases of hyperplasia or cancer," said presenter Steven Goldstein, MD, from New York University School of Medicine in New York City.

At 1 year, the incidence of endometrial proliferation and hyperplasia in this American study is comparable to that seen in a similar European study (no cases of hyperplasia or cancer and a 1.6% rate of proliferative tissue). It also compares favorably to the 3% rate of endometrial proliferation in studies of raloxifene (Evista), Dr. Goldstein noted.

In the study, postmenopausal women from 51 sites across the United States were randomized to ospemifene 30 mg or 60 mg or to placebo. Endometrial safety was assessed with transvaginal ultrasound at 6 and 12 months and with endometrial biopsy at 12 months.

One year after biopsy, the ospemifene groups (n = 55) had a 1.8% rate (n = 1) of endometrial proliferation of the disordered type, according to Dr. Goldstein. Three subjects in the ospemifene groups experienced several days of bleeding, but in all cases the endometrial biopsy was reported as atrophic.

There was a fairly high dropout rate in the study, probably related to frustration with the lack of efficacy of placebo, Dr. Goldstein speculated. Although 180 subjects began the study, only 140 completed treatment at 1 year. The dropout rate was particularly high in the placebo group (30.6%), compared with the 30 mg and 60 mg ospemifene groups (21% and 17.4%, respectively).

Because SERMs can have estrogenic effects on the endometrium, long-term therapy for vulvovaginal atrophy with any of these medications should be carefully evaluated for endometrial safety, Dr. Goldstein noted.

"Our study supports the potential use of ospemifene for vulvovaginal atrophy," Dr. Goldstein concluded.

"Vulvovaginal atrophy is an unmet need in postmenopausal women," said Vivian von Gruenigen, MD, chair of obstetrics and gynecology and a specialist in gynecologic oncology at the Summa Health System in Akron, Ohio.

"We need drug development for vulvovaginal atrophy," she said, "but the challenge we have with SERMs is their side-effect profile. Any time you dispense this type of medication, the potential concern is side effects such as endometrial hyperplasia, endometrial cancer, and pulmonary embolism," Dr. von Gruenigen explained.

Dr. von Gruenigen noted that this study was limited by the fact that it only focused on endometrial biopsy. "They didn't look at other long-term outcomes, such as lab parameters, that might indicate coagulation, which can be a surrogate for thromboembolic outcomes," she said.

"The study doesn't give us enough information, but it does give me hope and encouragement that this type of platform will continue to be studied. That's important because vulvovaginal atrophy really affects quality of life," Dr. von Gruenigen said.

Dr. Goldstein reports receiving consulting fees, honoraria, and equipment loans from Amgen, Bayer, Cook ObGyn, Lilly, Novo Nordisk A/S, Merck & Co., Pfizer, Philips Ultrasound, Shionogi, and Warner Chilcott. Dr. von Gruenigen has disclosed no relevant financial relationships.

American Congress of Obstetricians and Gynecologists (ACOG) 60th Annual Clinical Meeting. Presented May 7, 2012.

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