Ulipristal acetate for emergency contraception: postmarketing experience after use by more than 1 million women.

OBJECTIVE: To describe the safety of ulipristal acetate in emergency contraception. STUDY DESIGN: Postmarketing pharmacovigilance data collection. RESULTS: A total of 553 women experienced 1049 adverse drug reactions. The most frequent (n,%) were pregnancies (282, 6.8%); nausea, abdominal pain and vomiting (139, 13.3%); headache, dizziness (67, 6.4%); and metrorrhagia, menses delay and breast symptoms (84, 8.0%). Including data from clinical trials, 376 pregnancies have been reported in total, 232 (62%) with a known outcome: 28 live births (29 newborns), 34 miscarriages, 151 induced abortions, 4 ectopics and 15 which are ongoing. CONCLUSIONS: No safety concern emerges from a sizable database of reported adverse reactions following ulipristal acetate exposure among varying ethnicities and regions. Postapproval data confirm the safety profile described during the clinical trials. IMPLICATIONS: Use of ulipristal acetate for emergency contraception in a variety of settings and among diverse populations indicate that it is safe and without unexpected or serious adverse events.

Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel.

BACKGROUND: Emergency contraception (EC) does not always work. Clinicians should be aware of potential risk factors for EC failure. STUDY DESIGN: Data from a meta-analysis of two randomized controlled trials comparing the efficacy of ulipristal acetate (UPA) with levonorgestrel were analyzed to identify factors associated with EC failure. RESULTS: The risk of pregnancy was more than threefold greater for obese women compared with women with normal body mass index (odds ratio (OR), 3.60; 95% confidence interval (CI), 1.96-6.53; p<.0001), whichever EC was taken. However, for obese women, the risk was greater for those taking levonorgestrel (OR, 4.41; 95% CI, 2.05-9.44, p=.0002) than for UPA users (OR, 2.62; 95% CI, 0.89-7.00; ns). For both ECs, pregnancy risk was related to the cycle day of intercourse. Women who had intercourse the day before estimated day of ovulation had a fourfold increased risk of pregnancy (OR, 4.42; 95% CI, 2.33-8.20; p<.0001) compared with women having sex outside the fertile window. For both methods, women who had unprotected intercourse after using EC were more likely to get pregnant than those who did not (OR, 4.64; 95% CI, 2.22-8.96; p=.0002). CONCLUSIONS: Women who have intercourse around ovulation should ideally be offered a copper intrauterine device. Women with body mass index >25 kg/m(2) should be offered an intrauterine device or UPA. All women should be advised to start effective contraception immediately after EC.

Pregnane progestin contraception in systemic lupus erythematosus: a longitudinal study of 187 patients.

BACKGROUND: Systemic lupus erythematosus (SLE) affects women of child-bearing age. Combined oral contraceptives can worsen the course and increase the risk of thrombosis. The objectives of this study were to provide an alternative contraception and thus evaluate the gynecological tolerability of pregnane progestins (PPs) in SLE patients. Systemic lupus erythematosus disease activity and vascular tolerance were also reported. STUDY DESIGN: We used two PP with antigonadotropic potencies, chlormadinone acetate (CMA, 10 mg/day) and cyproterone acetate (CPA, 50 mg/day), administered orally for contraception in 187 SLE patients observed for 46±34.6 months (mean±S.E.), i.e., 6854 women-months. RESULTS: The gynecological tolerability was satisfactory: breakthrough bleeding was reported in 17.7% patients using CPA and 12.6% patients using CMA. No pregnancy was observed in the women followed in this cohort study. One deep vein thrombosis, one myocardial infarction, and one tibial posterior arterial occlusion were observed, giving an incidence for venous thromboembolism of 1.39/year×1000 women (95% CI 0-4.12) and for macroarterial disease an incidence of 2.79/year×1000 women (95% CI 0-6.65). Disease activity was less than before progestins. CONCLUSIONS: Pregnane progestin contraception is effective and well tolerated, thus providing SLE patients an excellent contraceptive alternative to the currently used methods.

Death-associated protein kinase loss of expression is a new marker for breast cancer prognosis.

PURPOSE: Death-associated protein (DAP)-kinase is a new Ser/Thr kinase involved in cell apoptosis and tumor suppression, the expression of which has been correlated to invasive potential and metastasis in several human neoplastic tissues. We analyzed the level of DAP-kinase expression in breast cancer specimens and its correlation with survival. EXPERIMENTAL DESIGN: One hundred twenty-eight breast cancer specimens were analyzed by immunohistochemistry. Patient records were studied retrospectively for demographic characteristics, clinical data, hormonal treatment, outcome, and survival. DAP-kinase protein expression was also studied in normal breast cells primary cultures under estrogen and antiestrogen treatment. RESULTS: Among the 128 patients, 30 showed a DAP-kinase staining < or = 20%, whereas 98 had a staining over 20%. Mean follow-up time was 62 months. The association between tumor Scarff-Bloom and Richardson grade (P = 0.009), estrogen receptor and progesterone receptor expression (P = 0.002 and 0.001, respectively), tumor size (P = 0.05), Bcl-2 expression (P = 0.004), and DAP-kinase immunostaining in the ductal carcinoma group was highly significant. Overall (64 months) and disease-free (63 months) survival in the high DAP-kinase expression group were significantly longer compared with the women whose tumors showed a loss of DAP-kinase expression (51 and 43 months, respectively). DAP-kinase protein was strongly expressed in normal breast tissue and in human breast epithelial cells primary cultures. Estradiol decreased DAP-kinase expression in these cells, arguing for hormonal regulation of the protein. CONCLUSIONS: Loss of DAP-kinase expression negatively correlates to survival and positively correlates to the probability of recurrence in a very significant manner. DAP-kinase thus constitutes a novel and independent prognosis marker for breast cancer.

Surfing on the morning after: analysis of an emergency contraception website.

The introduction of widespread nonprescription delivery of hormonal emergency contraception (EC) calls for development of innovative tools to provide information to and gather feedback from EC users. Individuals seeking confidential information on sexual health and contraception are increasingly turning to the Internet as the resource of choice. This study employed analytical software and manual content analysis to examine the use of a website dedicated to an EC product (www.norlevo.com) over the course of 2 years. Frequency of visits to and pageviews of the site increased consistently over the 2-year time period, and the bulk of the visitors to the site were EC users seeking responses to frequently asked questions. The most common concern raised by users was the occurrence of spotting and menstrual bleeding following EC use. This analysis reveals that within the context of nonprescription access to hormonal EC, a website can constitute a potent educational tool for health professionals and EC users and provide a valuable source of post-marketing feedback on product use.