SAT-219 A Novel 1-Year Contraceptive Vaginal System Delivering Segesterone Acetate and Ethinyl Estradiol: Effects on Lipids and other Hepatic Proteins

Abstract

Annovera™ is an FDA-approved contraceptive vaginal system (CVS) releasing 150 mcg segesterone acetate (SA), a new chemical entity, and 13 mcg ethinyl estradiol (EE) per day.1 We postulate that as a non-androgenic progestin, SA is unlikely to adversely affect lipids versus androgenic progestins. Here we review the effects of this CVS on lipids, glucose, coagulation factors and sex hormone-binding globulin (SHBG). Two pivotal, open-label, phase 3 trials and one PK trial evaluated women (18-40 years) who received the CVS for 13 cycles of 28 days over 12 months; one phase 3 study examined hepatic proteins in a substudy. The CVS was self-inserted, left in place for 21 days and removed for 7 days in each 28-day cycle. Lipids and glucose were measured at baseline and study end in the 3 trials. As previously reported, factor VIII, protein S (PS), fibrinogen, and SHBG were measured in the hepatic factors substudy.2 A total of 2308 women used the SA/EE CVS. Participants had a mean age of 26.7 years and mean BMI of 24.1 kg/m2. Most women were white (71%) and 14% were black. Women in the substudy (n=129) had similar mean ages and BMIs; 69% were white and 28% were black. In an integrated analysis of the phase 3 and PK studies, levels of total cholesterol increased by a mean +0.236 mmol/L from baseline to study end, as did HDL cholesterol (+0.162 mmol/L) and triglycerides (+0.193 mmol/L). At study end, LDL cholesterol decreased from baseline by a mean of -0.003 mmol/L. Glucose levels increased from baseline to study end by a mean +0.074 mmol/L. A prior study using the CVS showed lipid changes similar in direction and magnitude to other combined oral contraceptives (COC).3 Hepatic protein substudy results showed significant mean changes from baseline to study end for fibrinogen (+0.2±0.66 mg/mL [SD]; P=0.0052), factor VIII activity (+21%±55; P=0.0005), and PS activity (-8%±19; P=0.0043). Mean SHBG levels also significantly increased from baseline to study end by +81.7±94.3 nmol/L (P<0.0001).2 Another study comparing the CVS to an oral COC showed that the CVS had a hemostatic profile corresponding closely with that of the oral COC.4 Integrated safety data from two clinical studies, a hepatic substudy from one of the trials, and prior reports showed no clinically significant impact of the SA/EE CVS on lipids or glucose. The impact of the CVS on coagulation factors mirrored that of oral COCs. The significant increase in SHBG levels with the CVS was consistent with changes seen with other COCs containing EE and a non-androgenic progestin. The SA/EE CVS with a low dose of EE and the novel progestin, SA, has an acceptable metabolic profile with up to one year of use. 1. AnnoveraTM Prescribing Information. 2. Archer DF, et al. Contraception 2016;93(1):58-64. 3. Sitruk-Ware RL, et al. Contraception 2007;75(6):430-437. 4. Rad M, et al. Am J Obstet Gynecol 2006;195(1):72-77.