PLOS ONE Medicine&Health

The injectable contraceptives depot medroxyprogesterone acetate and norethisterone enanthate substantially and differentially decrease testosterone and sex hormone binding globulin levels: A secondary study from the WHICH randomized clinical trial

by Chanel Avenant, Mandisa Singata-Madliki, Alexis J. Bick, Donita Africander, Yusentha Balakrishna, Karl-Heinz Storbeck, Johnson M. Moliki, Sigcinile Dlamini, Salndave Skosana, Jenni Smit, Mags Beksinska, Ivana Beesham, Ishen Seocharan, Joanne Batting, George J. Hofmeyr, Janet P. Hapgood

HIV acquisition risk with norethisterone (NET) enanthate (NET-EN) is reportedly less than for depo-medroxyprogesterone acetate intramuscular (DMPA-IM). We investigated the effects of these progestin-only injectable contraceptives on serum testosterone and sex hormone binding globulin (SHBG) levels, since these may play a role in sexual behavior and HIV acquisition. The open-label WHICH clinical trial, conducted at two sites in South Africa from 2018–2019, randomized HIV-negative women aged 18–40 years to 150 mg DMPA-IM 12-weekly (n = 262) or 200 mg NET-EN 8-weekly (n = 259). We measured testosterone by UHPLC-MS/MS and SHBG by immunoassay in matched pairs of serum samples collected at baseline (D0) and at peak serum progestin levels at 25 weeks post initiation (25W) (n = 214–218 pairs). Both contraceptives substantially decreased, from D0 to 25W, the total testosterone [DMPA-IM D0 0.560, 25W 0.423 nmol/L, -24.3% (p