Use of serum evaluation of contraceptive and ovarian hormones to assess reduced risk of pregnancy among women presenting for emergency contraception in a multicenter clinical trial

Jeffrey T Jensen; Alison Edelman; Carolyn L Westhoff; Coutney A Schreiber; David F Archer; Stephanie Teal; Michael Thomas; Jill Brown; Diana L Blithe

doi:10.1016/j.contraception.2024.110475

Use of serum evaluation of contraceptive and ovarian hormones to assess reduced risk of pregnancy among women presenting for emergency contraception in a multicenter clinical trial

Contraception. 2024 Apr 24:110475. doi: 10.1016/j.contraception.2024.110475. Online ahead of print.

Authors

Jeffrey T Jensen¹, Alison Edelman², Carolyn L Westhoff³, Coutney A Schreiber⁴, David F Archer⁵, Stephanie Teal⁶, Michael Thomas⁷, Jill Brown⁸, Diana L Blithe⁸

Affiliations

¹ Oregon Health and Science University. Electronic address: jensenje@ohsu.edu.
² Oregon Health and Science University.
³ Columbia University.
⁴ University of Pennsylvania.
⁵ Clinical Research Center, Department of Obstetrics and Gynecology, Eastern Virginia Medical School.
⁶ University of Colorado.
⁷ University of Cincinnati.
⁸ Eunice Kennedy Shriver National Institute of Child Health and Human Development.

PMID: 38670302
DOI: 10.1016/j.contraception.2024.110475

Abstract

Objective: To evaluate ovulation risk among women enrolling in an emergency contraception (EC) study by measuring contraceptive steroids and ovarian hormones.

Study design: We used standard chemoluminescent assays to evaluate endogenous hormones [estradiol (E2), progesterone (P4), FSH, LH] and liquid chromatography-tandem triple quadrupole mass spectrometry (LC-MS/MS) to simultaneously analyze concentrations of ethinylestradiol (EE), dienogest (DNG), norelgestromin (NGMN), norethindrone (NET), gestodene (GSD), levonorgestrel (LNG), etonogestrel (ENG), segesterone acetate (NES), medroxyprogesterone acetate (MPA), and drospirenone (DRSP), in serum samples obtained at the time of enrollment in a recent study comparing oral ulipristal acetate and LNG EC in women with weight ≥ 80kg reporting no recent use of hormonal contraception.

Results: We enrolled 532 and obtained a valid baseline blood sample from 520 women. Of these, 117 (22.5%) had detectable concentrations of a progestin [MPA (n=58, 11.2%), LNG (50, 9.6%), ENG (11, 2.1%), NET (5, 0.96%), NGMN (3, 0.06%), or DRSP (1, 0.02%)]. LNG was co-detected in all three participants with samples containing NGMN. Multiple progestins were detected in 8 other women: ENG/MPA (1); ENG/LNG (2); MPA/LNG (5). Samples from 55 (10.6%) had concentrations of one or more progestin considered above the minimum level for contraceptive [MPA ≥ 0.1ng/mL, n = 19; NGMN/LNG ≥ 0.2ng/mL, n = 31; ENG ≥ 0.09 ng/mL, n = 8; NET ≥ 0.35 ng/mL, n = 4]. We detected concentrations of serum P4 ≥ 3ng/mL, indicative of luteal phase (post-ovulation) status, in an additional 194 (37.3%) samples.

Conclusions: More than one third of enrolled in our clinical trial of oral emergency contraception had evidence of prior ovulation at the time of enrollment. Additionally, about 23% had evidence of recent use of hormonal contraception recent use of hormonal contraception. This results would have decreased the expected risk of pregnancy in the study.

Implications: Many participants in a recent clinical trial of oral emergency contraception did not appear to be at risk for pregnancy or would not have benefited from intervention due to cycle timing. Investigators should consider the effects of these findings on expected pregnancy rates when determining sample size in future EC clinical trials, particularly when using non-inferiority designs or historical controls.

Keywords: compliance; emergency contraception; levonorgestrel; progestins; ulipristal acetate.