Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 Sep:137:110475.
doi: 10.1016/j.contraception.2024.110475. Epub 2024 Apr 24.

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  1 , Alison Edelman  2 , Carolyn L Westhoff  3 , Coutney A Schreiber  4 , David F Archer  5 , Stephanie Teal  6 , Michael Thomas  7 , Jill Brown  8 , Diana L Blithe  8
Affiliations
Randomized Controlled Trial

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 et al. Contraception. 2024 Sep.

Abstract

Objectives: 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 chemiluminescent assays to evaluate endogenous hormones (estradiol, progesterone, follicle stimulating hormone, luteinizing hormone) and liquid chromatography-tandem triple quadrupole mass spectrometry to simultaneously analyze concentrations of ethinylestradiol, dienogest, norelgestromin (NGMN), norethindrone (NET), gestodene, levonorgestrel (LNG), etonogestrel (ENG), segesterone acetate, medroxyprogesterone acetate (MPA), and drospirenone in serum samples obtained at the time of enrollment in a recent study comparing oral ulipristal acetate and LNG EC in women with weight ≥80 kg 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 progestin (MPA [n = 58, 11.2%], LNG [50, 9.6%], ENG [11, 2.1%], NET [5, 0.96%], NGMN [3, 0.06%], or drospirenone [1, 0.02%]). LNG was co-detected in all three participants with samples containing NGMN. Multiple progestins were detected in eight other women: ENG/MPA (1), ENG/LNG (2), and MPA/LNG (5). Samples from 55 (10.6%) had concentrations of one or more progestin considered above the minimum level for contraceptive (MPA ≥ 0.1 ng/mL, n = 19; NGMN/LNG ≥ 0.2 ng/mL, n = 31; ENG ≥ 0.09 ng/mL, n = 8; NET ≥ 0.35 ng/mL, n = 4). We detected concentrations of serum progesterone ≥ 3 ng/mL, indicative of luteal phase (postovulation) status, in an additional 194 (37.3%) samples.

Conclusions: More than one-third of enrolled in our clinical trial of oral EC had evidence of prior ovulation at the time of enrollment. Additionally, about 23% had evidence of recent use of hormonal contraception. These 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 noninferiority designs or historical controls.

Keywords: Compliance; Emergency contraception; Levonorgestrel; Progestins; Ulipristal acetate.

PubMed Disclaimer

Conflict of interest statement

CW – Consultant to Merck, Bayer, AbbVie, Therapeutics MD. Has also received research support from Estetra SPRL, Sebela, Chemoresearch Exeltis, and Medicines360, all managed through Columbia University.

DA- Grants from Bayer Healthcare, Mithra, Myovant, ObsEva, TherapeuticsMD; consultant to Agile Therapeutics, Mayne, Mithra, TherapeuticsMD; Investments in Agile Therapeutics, InnovaGyn, Inc.

AE- reports travel reimbursements from ACOG, WHO, and CDC for committee activities and honoraria for data safety monitoring committee from Gynuity. She receives royalties from UpToDate, Inc. Oregon Health & Science University (OHSU) receives research funding from OHSU Foundation, Gates, Merck, Organon, HRA Pharma, and NIH for which Alison Edelman is the principal investigator.

CS-Reports grants and contracts to the University of Pennsylvania (Schreiber) from NICHD, Independence Blue Cross, Society of Family Planning, Sebela and Athenium Pharmaceuticals. She receives royalties from UpToDate, Inc and thought the University of Pennsylvania for a data license agreement with Athenium Pharmaceuticals.

JJ – Dr. Jensen has received payments for consulting from Bayer Healthcare, Evofem, Hope Medicine, Foundation Consumer Healthcare, Mayne Pharma, Myovant, ViiV Healthcare, and TherapeuticsMD. OHSU has received research support from Abbvie, Bayer Healthcare, Daré, Estetra SPRL, Hope Medicine, Organon, Medicines360, Merck, Myovent, and Sebela. These companies and organizations may have a commercial or financial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by OHSU.

ST- No conflicts to report

MT-Dr. Thomas is the Vice President for ASRM and serves on the Board of Directors for ABOG

DB-NICHD has two Cooperative Research and Development Agreements (CRADAs) with industry HRA Pharma and Daré in which Dr. Blithe has served as Principal Investigator. Joint inventions resulting from the CRADA with HRA Pharma have generated royalty payments to NICHD and to Dr. Blithe as a co-inventor of therapeutic indications for Ulipristal Acetate

JB- no conflicts of interest

Figures

Figure 1.
Figure 1.
Results of testing baseline blood samples obtained from participants enrolled in a multicenter study of oral emergency contraception efficacy for contraceptive progestins. Percentages refer to all enrolled participants. LLQ = lower limit of quantification; MLCE = minimal level for contraceptive effect (see Box 1).
Figure 2:
Figure 2:
Evaluation of pregnancy risk among women enrolled in a multicenter study of oral emergency contraception emergency contraception based on progesterone (P4) concentration and presence of contraceptive progestins in a blood sample collected at enrollment. LNG = levonorgestrel, UPA = ulipristal acetate; LH = luteinizing hormone; E2 = estradiol (E2); LLQ = lower limit of quantification; MLCE = minimal level for contraceptive effect1. 1 See Box 1 2 One sample missing for evaluation of ovarian steroids and LH had no detectable progestin
See this image and copyright information in PMC

References

    1. Creinin MD. A reassessment of efficacy of the Yuzpe regimen of emergency contraception. Human reproduction (Oxford, England). 1997;12(3):496–8. - PubMed
    1. Glasier A. Emergency postcoital contraception. The New England journal of medicine. 1997;337(15):1058–64. - PubMed
    1. Trussell J, Ellertson C, von Hertzen H, Bigrigg A, Webb A, Evans M, et al. Estimating the effectiveness of emergency contraceptive pills. Contraception. 2003;67(4):259–65. - PubMed
    1. Wilcox AJ, Dunson DB, Weinberg CR, Trussell J, Baird DD. Likelihood of conception with a single act of intercourse: providing benchmark rates for assessment of post-coital contraceptives. Contraception. 2001;63(4):211–5. - PubMed
    1. Edelman A, Jensen JT, Brown J, Thomas M, Archer D, Schreiber C, et al. Emergency contraception for individuals weighing 80kg or greater: a randomized trial of 30 mg ulipristal 2 acetate and 1.5 mg or 3.0 mg levonorgestrel. Contraception. 2024;in review. - PMC - PubMed

Publication types

LinkOut - more resources