Cervical and systemic concentrations of long acting hormonal contraceptive (LARC) progestins depend on delivery method: Implications for the study of HIV transmission

Abstract

Progestin-only long-acting reversible contraceptives (LARCs) are increasingly popular among women seeking contraception; however, recent epidemiological studies suggest that systemically administered medroxyprogesterone acetate (MPA) may increase HIV acquisition. In order to determine the exact mechanisms underlying increases in transmission specific to MPA use and to test safer, alternative contraceptive progestin types and delivery methods, in vitro modeling studies must be performed. To achieve this, it is imperative that accurate hormone concentrations be utilized when modeling progestin-mediated outcomes, as the down-stream effects are dose-dependent. The local concentrations of progestins to which the lower female genital tract tissues are exposed after initiation of LARCs are unknown, but they likely differ from peripheral concentrations, dependent upon the progestin type and delivery method. Here, we measured in vivo endocervical and plasma concentrations of (1) systemically-delivered depo MPA (DMPA), (2) levonorgestrel (LNG) delivered via intrauterine system (IUS) and (3) etonogestrel (ETG) delivered via vaginal ring in women who recently initiated contraception treatment. Levels of ETG and LNG in cervical secretions were 100–200 fold higher than plasma levels. In contrast, measurable MPA levels were approximately 10-fold higher in plasma compared to cervical secretions. These results will inform the design of accurate in vitro studies on the influence of progestins on epithelial cells, tissue explants, and peripheral blood cells, to be able to better predict in vivo outcomes. Subsequent observations will aid in determining how MPA might influence HIV acquisition and may facilitate identification of optimal progestin-containing LARC alternatives for women at high risk for HIV infection.

Safety and continued use of the levonorgestrel intrauterine system as compared with the copper intrauterine device among women living with HIV in South Africa: A randomized controlled trial

“…In this cohort, neither reported oral contraceptive (aOR = 1.57, 95% CI 0.75-3.27) nor DMPA use (aOR = 1.32, 95% CI 0.42-4.16) was associated with detectable gVL in analysis adjusted for pVL. Our findings bear distinction from a mucosal immunology standpoint, as the LNG-IUS has markedly higher LNG concentrations in genital tract mucosa, reflecting its largely localized effect, in contrast to the LNG implant and DMPA [41]. When compared with the C-IUD, LNG does not appear to drive shedding via gVL; neither IUC appears to increase gVL through hypothesized inflammatory response from foreign body effect.…”

Effects of Different Progesterone Containing Contraceptive Methods on Safety and Endogenous Progesterone Level: A Prospective Cohort Study

“…Endometrium thickness was insigni cantly different among the four groups at 1st month till 6th month. Figure 3 Discussion are increasingly prevalent among females looking for contraception [15]. Progestogens are the primary active ingredient in hormonal contraception due to their three primary modes of action.…”

Effects of Different Progesterone Containing Contraceptive Methods on Safety and Endogenous Progesterone Level

“…Table 5 Endometrium thickness was insigni cantly different among the four groups at 1 st month till 6 th month. Figure 3 Discussion LARCs are increasingly prevalent among females looking for contraception [15] . Progestogens are the primary active ingredient in hormonal contraception, as they have essentially three modes of action, their structure and the action pro le are different, they show a multifocal form of action in contraception.…”