Effects of Depot Medroxyprogesterone Acetate Intramuscular Injection, Copper Intrauterine Device and Levonorgestrel Implant Contraception on Estradiol Levels: An Ancillary Study of the ECHO Randomized Trial

Abstract

IntroductionHormonal contraception affects endogenous sex steroid levels. Robust evidence from randomized trials of the relative effects of different contraceptive methods is scarce. We compared the effects of three contraceptive methods on serum estradiol levels using data from women (18–35 years) requesting contraception in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial.MethodsWomen were randomly allocated to the depot medroxyprogesterone acetate intramuscular (DMPA-IM) injection, copper intrauterine device (IUD) or levonorgestrel (LNG) implant. In this sub-study, stored baseline and 6-month serum samples were analyzed in 401 participants from East London, South Africa (DMPA-IM: 131, IUD: 135 and LNG: 135).ResultsBaseline median (interquartile range, IQR) estradiol levels were similar between the three groups [DMPA-IM 229 (152–455), IUD 235 (168–426) and LNG 216 (153–419 pmol/L)]. At 6-months, median estradiol in the IUD group was unchanged (298 (163–467) pmol/L), whilst levels in the DMPA-IM and implant groups were significantly reduced from baseline. The median estradiol level in the DMPA-IM group [139 (97–193) pmol/L] was significantly lower than in both IUD (p < 0.0001) and implant (p = 0.005) groups; and level in the implant group [156 (112–250) pmol/L] was significantly lower than in the IUD group (p = 0.004).ConclusionsAt 6-months (DMPA-IM nadir), median estradiol with DMPA-IM was 53% lower and with the LNG implant, 48% lower than with the IUD. The greater reduction in estradiol levels with the DMPA-IM injection compared to the LNG implant and IUD has implications for the relative psychological, sexual as well as physiological side-effects of these contraceptive methods.ECHO Study RegistrationClinicalTrials.gov, identifier: NCT02550067.

Effects of injectable contraception with depot medroxyprogesterone acetate or norethisterone enanthate on estradiol levels and menstrual, psychological and behavioral measures relevant to HIV risk: The WHICH randomized trial

“…The effects were not significantly different between groups. Our findings of estradiol serum concentrations for DMPA-IM of 76.5 pmol/L (IQR 54.1 to 104.2) are similar to values reported in the literature, which range from 37-367 pmol/L [32,36,[49][50][51][52][53][54]. However, our findings of estradiol serum concentrations for NET-EN of 69.8 pmol/L (55.1 to 89.3), are lower than some but not all of those usually reported, which range from 135-2820 pmol/L [35,[55][56][57].…”

“…The latter likely include effects on vaginal microbiome composition, genital tract integrity, immune function and susceptibility to and transmission of HIV and other infections [ 12 , 13 ]. DMPA-IM use is associated with lower estrogen levels compared with no HC, as well as users of other HCs such as the LNG intrauterine system, and the etonogestrel and LNG implants [ 12 , 13 , 32 ]. Some reports suggest that DMPA-IM results in hypoestrogenic effects with estradiol levels similar to postmenopausal levels [ 13 , 33 ].…”

Sexual behaviour among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Data from the ECHO randomized trial

“…This is biologically plausible because of the known effects of DMPA-IM on suppression of endogenous estrogen and testosterone, both of which are considered to enhance libido. Ancillary hormonal studies of the ECHO Trial at the East London, South Africa site found lower estradiol levels at 6 months in women randomized to DMPA-IM than those randomized to the Cu-IUD and the LNG implant, and the implant group were significantly lower than with the Cu-IUD [18]. Free testosterone was significantly lower with DMPA-IM than with the LNG implant, with the Cu-IUD being intermediate.…”