Impact Of Long-acting Reversible Contraceptives On Bone Density During Simulated Microgravity

Abstract

Hormonal contraception is routinely used by premenopausal women, including female astronauts, to suppress ovarian function and menstrual cycling. Combined oral contraceptive pill (COC, ethinyl estradiol and progestin) use leads to a suppression of bone turnover and reduced bone mineral density (BMD) gain with long-term exercise. Long-acting, reversible contraceptives (LARC, progestin-only) provide many practical advantages over COC. With increasing numbers of women in the US astronaut corps, we risk sending female crew members into microgravity without a clear understanding of the impact of LARC use on bone health. PURPOSE: We hypothesize that LARC use will blunt decreases in BMD associated with hindlimb unloading (HU). METHODS: Virgin female Sprague-Dawley rats (n=26; 4-mo-old) were singly housed and randomly assigned to placebo and LARC groups, via a slow-release etonogestrel pellet (0.00ug/d vs. 0.30ug/d) implanted under the skin. Animals were further randomized into ambulatory and HU subgroups (n=6-7/subgroup), with HU initiated a week following pellet insertion and lasting for 6 weeks. Pre/post HU, proximal tibia metaphysis (PTM) were scanned in vivo with peripheral quantitative computed tomography (pQCT). Univariate and repeated measures 2-way ANOVA were used. RESULTS: There was a time*loading group interaction (p<0.01) for body weight and food consumption. HU animals weighed less over the last 4 weeks of the study but consumed more food over 6 weeks of HU vs. ambulatory animals. Soleus wet weights were significantly lower in HU compared to ambulatory animals (p<0.001). There was a main effect of time for (p<0.001) PTM total, cancellous, and cortical volumetric BMD and total and cortical areas. For marrow area at the PTM there was a time*loading group interaction (p=0.044), such that over time the HU animals had a decrease in marrow area compared to the ambulatory animals. No impact of LARC on these outcomes was detected. CONCLUSIONS: Early results indicate that LARC use does not alter the PTM bone response to mechanical unloading of simulated microgravity assessed by in vivo pQCT. This work is supported by the Translational Research Institute for Space Health through Cooperative Agreement NNX16AO69A.