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Objective: To evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen. Study design: We pooled efficacy outcomes from 2 pivotal phase 3 contraceptive trials with E4/DRSP con-ducted in the United States/Canada and Europe/Russia. We assessed Pearl Index (PI; pregnancies per 100 participant-years) and 13-cycle life-table pregnancy rates in at-risk cycles (confirmed intercourse and no other contraceptive use) among participants 16 to 35 years. We calculated PI by age and further subcate-gorization (contraceptive history and body mass index [BMI]). We performed multivariable analysis using Cox regression to assess impact of potential confounding factors. Results: Analyses included 3027 participants, of whom 451 (14.9%) had a BMI >30 kg/m2. The pooled PI was 1.52 (95% confidence interval 1.04 -2.16) and the 13-cycle life-table pregnancy rate was 1.28% (0.83%- 1.73%). We calculated unadjusted pooled PI in participants 16 to 25 years and 26 to 35 years of 1.61 (0.94-2.57) and 1.43 (0.78-2.40), respectively; in new starters and switchers of 1.88 (1.09-3.00) and 1.24 (0.68-2.08), respectively; and by BMI < 25 kg/m2, 25 to 29.9 kg/m2, and >30 kg/m2 of 1.14 (0.64-1.88), 2.19 (1.05-4.03), and 2.27 (0.83-4.94), respectively. In multivariable analysis, we found associations of prior pregnancy (hazard ratio [HR] 3.61[1.56-8.38]), Black race (HR 4.61[1.97-10.80]), age 16 to 25 years (HR 2.37[1.09-5.15]) and compliance < 99% of expected pills (HR 4.21[2.04-8.66]) with conception. Conclusion: E4/DRSP is an effective oral contraceptive overall and across subgroups stratified by age, con-traceptive history, and BMI. Other than compliance, predictors of contraceptive failure are nonmodifiable. Implications Statement: Pooled results from two phase 3 trials demonstrate high contraceptive efficacy of the novel estetrol-drospirenone oral contraceptive. Several non-modifiable risk factors, including prior pregnancy, race, and age, are associated with higher pregnancy risk. Additional research is needed to better understand predictors of combined oral contraceptive failure. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Objective: To update and expand the 2013 position statement of The North American Menopause Society (NAMS) on the management of the genitourinary syndrome of menopause (GSM), of which symptomatic vulvovaginal atrophy (VVA) is a component. Methods: A Panel of acknowledged experts in the field of genitourinary health reviewed the literature to evaluate new evidence on vaginal hormone therapies as well as on other management options available or in development for GSM. A search of PubMed was conducted identifying medical literature on VVA and GSM published since the 2013 position statement on the role of pharmacologic and nonpharmacologic treatments for VVA in postmenopausal women. The Panel revised and added recommendations on the basis of current evidence. The Panel's conclusions and recommendations were reviewed and approved by the NAMS Board of Trustees. Results: Genitourinary syndrome of menopause affects approximately 27% to 84% of postmenopausal women and can significantly impair health, sexual function, and quality of life. Genitourinary syndrome of menopause is likely underdiagnosed and undertreated. In most cases, symptoms can be effectively managed. A number of over-the-counter and government-approved prescription therapies available in the United States and Canada demonstrate effectiveness, depending on the severity of symptoms. These include vaginal lubricants and moisturizers, vaginal estrogens and dehydroepiandrosterone (DHEA), systemic hormone therapy, and the estrogen agonist/antagonist ospemifene. Long-term studies on the endometrial safety of vaginal estrogen, vaginal DHEA, and ospemifene are lacking. There are insufficient placebo-controlled trials of energy-based therapies, including laser, to draw conclusions on efficacy and safety or to make treatment recommendations. Conclusions: Clinicians can resolve many distressing genitourinary symptoms and improve sexual health and the quality of life of postmenopausal women by educating women about, diagnosing, and appropriately managing GSM. Choice of therapy depends on the severity of symptoms, the effectiveness and safety of treatments for the individual patient, and patient preference. Nonhormone therapies available without a prescription provide sufficient relief for most women with mild symptoms. Low-dose vaginal estrogens, vaginal DHEA, systemic estrogen therapy, and ospemifene are effective treatments for moderate to severe GSM. When low-dose vaginal estrogen or DHEA or ospemifene is administered, a progestogen is not indicated; however, endometrial safety has not been studied in clinical trials beyond 1 year. There are insufficient data at present to confirm the safety of vaginal estrogen or DHEA or ospemifene in women with breast cancer; management of GSM should consider the woman's needs and the recommendations of her oncologist.