The injectable contraceptives depot medroxyprogesterone acetate and norethisterone enanthate substantially and...

Area of Science:

• Endocrinology
• Reproductive Health
• HIV Prevention

Background:

• Injectable progestin-only contraceptives like DMPA-IM and NET-EN are widely used globally.
• Concerns exist regarding their potential impact on sexual behavior and HIV acquisition risk, possibly mediated by hormonal changes.
• Previous research suggested lower HIV acquisition risk with NET-EN compared to DMPA-IM.

Purpose of the Study:

• To investigate the effects of DMPA-IM and NET-EN on serum testosterone and sex hormone binding globulin (SHBG) levels in HIV-negative women.
• To determine if observed changes in these hormones correlate with sexual behavior or function.
• To explore the role of endogenous testosterone and SHBG in the context of contraceptive-induced hormonal shifts.

Main Methods:

• An open-label randomized clinical trial (WHICH study) involving HIV-negative women aged 18-40 years.
• Participants received either DMPA-IM (150 mg, 12-weekly) or NET-EN (200 mg, 8-weekly).
• Serum testosterone and SHBG levels were measured at baseline and 25 weeks post-initiation using UHPLC-MS/MS and immunoassay, respectively.

Main Results:

• Both DMPA-IM and NET-EN significantly decreased total testosterone, SHBG, and calculated free testosterone levels from baseline to 25 weeks.
• NET-EN induced a more substantial decrease in testosterone (-54.1%) and SHBG (-65.1%) compared to DMPA-IM (-24.3% and -29.8%, respectively).
• Despite hormonal changes, no decrease in risky sexual behavior or sexual function was observed, suggesting other factors, like the androgenic nature of the progestins themselves, may dominate effects.

Conclusions:

• DMPA-IM and NET-EN significantly alter endogenous testosterone and SHBG levels, with NET-EN having a more pronounced effect.
• The observed hormonal changes do not appear to explain the sexual behavior or function in users of these contraceptives.
• The inherent androgenic properties of DMPA (medroxyprogesterone) and NET likely outweigh the impact of decreased endogenous testosterone on brain-mediated sexual effects.