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

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.