AUTHOR=Allaway Heather C. M. , Misra Madhusmita , Southmayd Emily A. , Stone Michael S. , Weaver Connie M. , Petkus Dylan L. , De Souza Mary Jane 

TITLE=Are the Effects of Oral and Vaginal Contraceptives on Bone Formation in Young Women Mediated via the Growth Hormone-IGF-I Axis?

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00334

DOI=10.3389/fendo.2020.00334

ISSN=1664-2392

ABSTRACT=<p><bold>Purpose:</bold> Combined hormonal contraceptive therapy has been associated with negative bone mineral density outcomes that may be route-dependent [i.e., combined oral contraception (COC) vs. contraceptive vaginal ring (CVR)] and involve the hepatic growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. The objective of the pilot study was to assess the impact of route of contraceptive administration on IGF-I and procollagen type I N-terminal propeptide (PINP) responses to an IGF-I Generation Test. We hypothesized that the peak rise in IGF-I and PINP concentration and area under the curve (AUC) would be attenuated following COC, but not CVR, use.</p><p><bold>Methods:</bold> Healthy, premenopausal women not taking hormonal contraception were recruited. Women were enrolled in the control group (<italic>n</italic> = 8) or randomly assigned to COC (<italic>n</italic> = 8) or CVR (<italic>n</italic> = 8) for two contraceptive cycles. IGF-I Generation Tests were used as a probe to stimulate IGF-I release and were completed during the pre-intervention and intervention phases. Serum IGF-I and PINP were measured during both IGF-I Generation Tests. The study was registered at <ext-link ext-link-type="uri" xlink:href="https://www.ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link> (<ext-link ext-link-type="DDBJ/EMBL/GenBank" xlink:href="NCT02367833" xmlns:xlink="http://www.w3.org/1999/xlink">NCT02367833</ext-link>).</p><p><bold>Results:</bold> Compared to the pre-intervention phase, peak IGF-I concentration in response to the IGF-I Generation Test in the intervention phase was suppressed in the COC group (<italic>p</italic> &lt; 0.001), but not the CVR or Control groups (<italic>p</italic> &gt; 0.090). Additionally, compared to the pre-intervention phase, PINP AUC during the intervention phase was suppressed in both COC and CVR groups (<italic>p</italic> &lt; 0.001), while no difference was observed in the control group (<italic>p</italic> = 0.980).</p><p><bold>Conclusion:</bold> These data suggest that changes in recombinant human GH-stimulated hepatic IGF-I synthesis in response to combined hormonal contraception (CHC) use are dependent on route of CHC administration, while the influence on PINP is route-independent. Future research is needed to expand these results with larger randomized control trials in all age ranges of women who utilize hormonal contraception.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://www.ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.ClinicalTrials.gov</ext-link> registration <ext-link ext-link-type="DDBJ/EMBL/GenBank" xlink:href="NCT02367833" xmlns:xlink="http://www.w3.org/1999/xlink">NCT02367833</ext-link>.</p>