Hormonal Contraception and Bone Metabolism: Emerging Evidence from a Systematic Review and Meta-Analysis of Studies on Post-Pubertal and Reproductive-Age Women
Background/Objectives: This study aims to assess the effects of combined hormonal contraceptives (CHCs) on bone metabolism markers. It primarily measures osteocalcin and additionally examines other bone health markers, seeking to determine their responses to estrogen–progestogen treatments. Methods:...
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2025-01-01
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| author | Alice Tassi Ambrogio P Londero Anjeza Xholli Giulia Lanzolla Serena Bertozzi Luca Savelli Federico Prefumo Angelo Cagnacci |
| author_facet | Alice Tassi Ambrogio P Londero Anjeza Xholli Giulia Lanzolla Serena Bertozzi Luca Savelli Federico Prefumo Angelo Cagnacci |
| author_sort | Alice Tassi |
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| description | Background/Objectives: This study aims to assess the effects of combined hormonal contraceptives (CHCs) on bone metabolism markers. It primarily measures osteocalcin and additionally examines other bone health markers, seeking to determine their responses to estrogen–progestogen treatments. Methods: This study involved a comprehensive evaluation of the pertinent literature and a meta-analysis explicitly conducted on data describing women of reproductive age. The analysis encompassed accessible papers ranging to December 2024 (i.e., those listed in PubMed/Medline, Embase, Scopus, the Cochrane Database, International Clinical Trials Registry, and ClinicalTrials.gov). We examined published randomized controlled trials (RCTs) and prospective studies. The quality of the studies was assessed using the Cochrane tool for RCTs and the Newcastle–Ottawa Scale for prospective studies. The selected indicators for primary and secondary outcomes were ascertained by standardized mean change (SMC), displaying the difference between conditions before and after treatment. Trends were evaluated using meta-regressions. Results: Ultimately, 34 articles out of 1924 identified items met the inclusion criteria, covering 33 unique studies. In EE/E4 combinations, osteocalcin dropped significantly (SMC −0.54 (CI.95 −0.64/−0.43) and −0.43 (CI.95 −0.76/−0.10)). Similar effects were observed for other bone-formation and reabsorption markers, with less significant reductions observed in E2-containing CHC (e.g., alkaline phosphatase (bone) EE combinations, SMC −0.39 (CI.95 −0.67/−0.11); P1NP E2 combination, 0.12 (CI.95 −0.10/0.33); and EE combinations, −0.55 (CI.95 −0.83/−0.26)). The reduction patterns also exhibited differences according to the women’s age (e.g., osteocalcin in EE combinations ≤21, SMC −0.63 (CI.95 −0.77/−0.49) and >21, SMC −0.42 (CI.95 −0.61/−0.24); alkaline phosphatase (bone) EE combinations ≤21, SMC −0.55 (CI.95 −0.86/−0.24) and >21, SMC −0.06 (CI.95 −0.47/0.35)). This analysis found that CHC maintains or reduces bone turnover in childbearing women, with effects varying by age and hormone combination. Moreover, bone-formation and reabsorption markers correlated positively to pro-androgenic progestins (<i>p</i> < 0.05). Thus, estrogen–progestogen combinations reduce bone turnover less when weak estrogens and a pro-androgenic or neutral progestin are present. Conclusions: This study found that CHCs reduce bone turnover, with natural estrogens and androgenic progestins appearing to be more beneficial than EE and anti-androgenic types. These findings would potentially influence decisions relevant to CHC prescriptions during a woman’s reproductive phases, emphasizing the need for additional research to tailor CHC usage to bone health. |
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| institution | Kabale University |
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| spelling | doaj-art-407bf5020b2f47c79fea11b446b69af82025-01-24T13:45:14ZengMDPI AGPharmaceuticals1424-82472025-01-011816110.3390/ph18010061Hormonal Contraception and Bone Metabolism: Emerging Evidence from a Systematic Review and Meta-Analysis of Studies on Post-Pubertal and Reproductive-Age WomenAlice Tassi0Ambrogio P Londero1Anjeza Xholli2Giulia Lanzolla3Serena Bertozzi4Luca Savelli5Federico Prefumo6Angelo Cagnacci7Obstetrics and Gynecology Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, ItalyDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Infant Health, University of Genoa, 16132 Genova, ItalyAcademic Unit of Obstetrics and Gynecology, IRCCS Ospedale San Martino, 16132 Genoa, ItalyDepartment of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, 56126 Pisa, ItalyBreast Unit, University Hospital of Udine, 33100 Udine, ItalyObstetrics and Gynecology Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, ItalyObstetrics and Gynecology Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, ItalyDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Infant Health, University of Genoa, 16132 Genova, ItalyBackground/Objectives: This study aims to assess the effects of combined hormonal contraceptives (CHCs) on bone metabolism markers. It primarily measures osteocalcin and additionally examines other bone health markers, seeking to determine their responses to estrogen–progestogen treatments. Methods: This study involved a comprehensive evaluation of the pertinent literature and a meta-analysis explicitly conducted on data describing women of reproductive age. The analysis encompassed accessible papers ranging to December 2024 (i.e., those listed in PubMed/Medline, Embase, Scopus, the Cochrane Database, International Clinical Trials Registry, and ClinicalTrials.gov). We examined published randomized controlled trials (RCTs) and prospective studies. The quality of the studies was assessed using the Cochrane tool for RCTs and the Newcastle–Ottawa Scale for prospective studies. The selected indicators for primary and secondary outcomes were ascertained by standardized mean change (SMC), displaying the difference between conditions before and after treatment. Trends were evaluated using meta-regressions. Results: Ultimately, 34 articles out of 1924 identified items met the inclusion criteria, covering 33 unique studies. In EE/E4 combinations, osteocalcin dropped significantly (SMC −0.54 (CI.95 −0.64/−0.43) and −0.43 (CI.95 −0.76/−0.10)). Similar effects were observed for other bone-formation and reabsorption markers, with less significant reductions observed in E2-containing CHC (e.g., alkaline phosphatase (bone) EE combinations, SMC −0.39 (CI.95 −0.67/−0.11); P1NP E2 combination, 0.12 (CI.95 −0.10/0.33); and EE combinations, −0.55 (CI.95 −0.83/−0.26)). The reduction patterns also exhibited differences according to the women’s age (e.g., osteocalcin in EE combinations ≤21, SMC −0.63 (CI.95 −0.77/−0.49) and >21, SMC −0.42 (CI.95 −0.61/−0.24); alkaline phosphatase (bone) EE combinations ≤21, SMC −0.55 (CI.95 −0.86/−0.24) and >21, SMC −0.06 (CI.95 −0.47/0.35)). This analysis found that CHC maintains or reduces bone turnover in childbearing women, with effects varying by age and hormone combination. Moreover, bone-formation and reabsorption markers correlated positively to pro-androgenic progestins (<i>p</i> < 0.05). Thus, estrogen–progestogen combinations reduce bone turnover less when weak estrogens and a pro-androgenic or neutral progestin are present. Conclusions: This study found that CHCs reduce bone turnover, with natural estrogens and androgenic progestins appearing to be more beneficial than EE and anti-androgenic types. These findings would potentially influence decisions relevant to CHC prescriptions during a woman’s reproductive phases, emphasizing the need for additional research to tailor CHC usage to bone health.https://www.mdpi.com/1424-8247/18/1/61estrogensprogestinsbone turnoverosteocalcinstandardized mean changeprogestins |
| spellingShingle | Alice Tassi Ambrogio P Londero Anjeza Xholli Giulia Lanzolla Serena Bertozzi Luca Savelli Federico Prefumo Angelo Cagnacci Hormonal Contraception and Bone Metabolism: Emerging Evidence from a Systematic Review and Meta-Analysis of Studies on Post-Pubertal and Reproductive-Age Women Pharmaceuticals estrogens progestins bone turnover osteocalcin standardized mean change progestins |
| title | Hormonal Contraception and Bone Metabolism: Emerging Evidence from a Systematic Review and Meta-Analysis of Studies on Post-Pubertal and Reproductive-Age Women |
| title_full | Hormonal Contraception and Bone Metabolism: Emerging Evidence from a Systematic Review and Meta-Analysis of Studies on Post-Pubertal and Reproductive-Age Women |
| title_fullStr | Hormonal Contraception and Bone Metabolism: Emerging Evidence from a Systematic Review and Meta-Analysis of Studies on Post-Pubertal and Reproductive-Age Women |
| title_full_unstemmed | Hormonal Contraception and Bone Metabolism: Emerging Evidence from a Systematic Review and Meta-Analysis of Studies on Post-Pubertal and Reproductive-Age Women |
| title_short | Hormonal Contraception and Bone Metabolism: Emerging Evidence from a Systematic Review and Meta-Analysis of Studies on Post-Pubertal and Reproductive-Age Women |
| title_sort | hormonal contraception and bone metabolism emerging evidence from a systematic review and meta analysis of studies on post pubertal and reproductive age women |
| topic | estrogens progestins bone turnover osteocalcin standardized mean change progestins |
| url | https://www.mdpi.com/1424-8247/18/1/61 |
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