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Hormonal Contraception and Bone

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Female and Male Contraception

Part of the book series: Trends in Andrology and Sexual Medicine ((TASM))

Abstract

Newer progestins possess a strong anti-gonadotropic activity. Combined oral hormonal contraceptives (COCs) containing 15–20 μg EE and a newer progestin suppress the hypothalamic-pituitary-ovarian axis despite the low EE content, so that in adolescents, endogenous oestradiol production is decreased to peri- and postmenopausal levels and reduces bone formation. Therefore, low-dose oral contraceptive use might interfere with normal acquisition of peak bone mass when given early after menarche. Adolescent girls using low-dose COCs (15–20 μg EE daily) have been shown to possess a lower mean gain in bone density and to reach only a subnormal peak bone mass compared to users of 30 μg EE pills or untreated controls. In consequence, COCs containing 15–20 μg EE should be avoided in adolescents before peak bone mass has been acquired. However, this evidence should not lead to the consequence that a safe contraceptive method is refused to young women: in adolescents, 30 μg EE pills are safe for the acquisition of a normal peak bone mass. Combined oral contraception has no adverse impact on BMD when given during adulthood and might prevent the bone loss occurring in perimenopause. Oral contraceptive past use is associated with an increased risk of fracture in adult women if COC intake has been started below the age of 30 years.

There is strong evidence from longitudinal data showing that depot medroxyprogesterone acetate (DMPA) compromises BMD in adult current users. If DMPA is administered to adolescent girls, bone formation and peak bone mass are reduced. The decrease in bone density appears to be at least partially reversible in both adult and adolescent women. DMPA has to be reserved for patients where no alternative contraceptive method is possible.

For all other hormonal contraceptive methods, good evidence is missing concerning their effect on bone. However, pilot studies suggest in some an adverse effect on peak bone mass.

The supply of sufficient calcium, vitamin D through food or with substitutes and proteins is important for the bone health in women of all ages needing contraception.

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References

  1. Benagiano G, Bastianelli C, Farris M. Contraception: a social revolution. Eur J Contracept Reprod Health Care. 2007;12(1):3–12.

    Article  PubMed  Google Scholar 

  2. Szarewski A, Mansour D, Shulman LP. 50 years of “The Pill”: celebrating a golden anniversary. J Fam Plann Reprod Health Care. 2010;36(4):231–8.

    Article  PubMed  Google Scholar 

  3. Chadwick KD, Burkman RT, Tornesi BM, Mahadevan B. Fifty years of “the Pill”: risk reduction and discovery of benefits beyond contraception, reflections and forecast. Toxicol Sci. 2012;125(1):2–9.

    Article  CAS  PubMed  Google Scholar 

  4. Horsman A, Jones M, Francis R, et al. The effect of estrogen dose on postmenopausal bone loss. N Engl J Med. 1983;309:1405–7.

    Article  CAS  PubMed  Google Scholar 

  5. Chew CK, Clarke BL. Causes of low peak bone mass in women. Maturitas. 2018;111:61–8.

    Article  PubMed  Google Scholar 

  6. Berger C, Goltzman D, Langsetmo L, Joseph L, Jackson S, Kreiger N, Tenenhouse A, Davison KS, Josse RG, Prior JC, Hanley DA, The CaMos Research Group. Peak bone mass from longitudinal data: implications for the prevalence, pathophysiology, and diagnosis of osteoporosis. J Bone Miner Res. 2010;25(9):1948–57.

    Article  PubMed  PubMed Central  Google Scholar 

  7. De Leo V, Musacchio MC, Cappelli V, Piomboni P, Morgante G. Hormonal contraceptives: pharmacology tailored to women’s health. Hum Reprod Update. 2016;22(5):634–46.

    Article  PubMed  CAS  Google Scholar 

  8. Sitruk-Ware R, Nath A. Characteristics and metabolic effects of estrogen and progestins contained in oral contraceptive pills. Best Pract Res Clin Endocrinol Metab. 2013;27:13–24.

    Article  CAS  PubMed  Google Scholar 

  9. Christin-Maitre S, Serfaty D, Chabbert-Buffet N, Ochsenbein E, Chassard D, Thomas J-L. Comparison of a 24-day and a 21-day pill regimen for the novel combined oral contraceptive, nomegestrol acetate and 17beta-estradiol (NOMAC/E2): a double-blind, randomized study. Hum Reprod. 2011;26(6):1338–47.

    Article  CAS  PubMed  Google Scholar 

  10. Sitruk-Ware R, Nath A. Metabolic effects of contraceptive steroids. Rev Endocr Metab Disord. 2011;12:63–75.

    Article  CAS  PubMed  Google Scholar 

  11. Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005;8(Suppl. 1):3–63.

    Article  CAS  PubMed  Google Scholar 

  12. Goldzieher JW, Brody SA. Pharmacokinetics of ethinyl estradiol and mestranol. Am J Obstet Gynecol. 1990;163(6 Pt 2):2114–9.

    Article  CAS  PubMed  Google Scholar 

  13. Trémolières FA, Capilla F, Cigagna F, Ribot C. Augmentation de la prolifération cellulaire par l’acétate de nomégestrol dans des cultures d’ostéoblastes humains. Reprod Hum Horm. 1997;10(3):118–24.

    Google Scholar 

  14. Trémollières F. Contraception orale estro-progestative: quelle différence entre éthinylestradiol et estradiol? [Oral combined contraception: is there any difference between ethinyl-estradiol and estradiol?]. Gynecol Obstet Fertil. 2012;40(2):109–15.

    Article  PubMed  Google Scholar 

  15. Allaway HCM, Misra M, Southmayd EA, Stone MS, Weaver CM, Petkus DL, De Souza MJ. Are the effects of oral and vaginal contraceptives on bone formation in young women mediated via the growth hormone-IGF-I Axis? Front Endocrinol. 2020;11:334–46.

    Article  Google Scholar 

  16. Apter D, Zimmerman Y, Beekman L, Mawet M, Maillard C, Foidart J-M, Coelingh Bennink HJT. Estetrol combined with drospirenone: an oral contraceptive with high acceptability, user satisfaction, well-being and favourable body weight control. The Eur J Contracept Reprod Health Care. 2017;22(4):260–7.

    Article  CAS  PubMed  Google Scholar 

  17. Mawet M, Maillard C, Klipping C, Zimmerman Y, Foidart J-M, Coelingh Bennink HJT. Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives. Eur J Contracept Reprod Health Care. 2015;20(6):463–75.

    PubMed  PubMed Central  Google Scholar 

  18. Coelingh Bennink HJT, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11(Suppl 1):47–58.

    Article  CAS  PubMed  Google Scholar 

  19. Coelingh Bennink HJ, Skouby S, Bouchard P, et al. Ovulation inhibition by estetrol in an in vivo model. Contraception. 2008;77:186–90.

    Article  CAS  PubMed  Google Scholar 

  20. Foidart J-M, Lobo RA, Rosing J, Taziaux M, Jost M, Douxfils J, Gaspard U. Estetrol is a unique native estrogen that does not modify coagulation markers in postmenopausal women and maintains sensitivity to activated protein C (APC), presented at the 2019 Annual Meeting of the North American Menopause Society, Chicago, United States (25 Sep 2019 to 28 Sep 2019).

    Google Scholar 

  21. Regidor P-A. The clinical relevance of progestogens in hormonal contraception: present status and future developments. Oncotarget. 2018;9(77):34628–38.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Regidor PA, Schindler AE. Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone. Oncotarget. 2017;8:83334–42.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Birkhaeuser M. Grundlagen zur Gestagen-Komponente in der hormonalen Kontrazeption. Ther Umsch. 2009;66:71–87.

    Article  Google Scholar 

  24. Trémollieres FA, Strong DD, Baylink DJ, Mohan S. Progesterone and promegestone stimulate bone cell proliferation and insulin-like growth factor-2 production. Acta Endocrinol. 1992;126:329–37.

    Article  Google Scholar 

  25. Ishida Y, Heersche JN. Progesterone stimulates proliferation and differentiation of osteoprogenitor cells in bone cell populations derived from adult female but not from adult male rats. Bone. 1997;20:17–25.

    Article  CAS  PubMed  Google Scholar 

  26. Verhaar HJ, Damen CA, Duursma SA, et al. A comparison of the action of progestins and estrogen on the growth and differentiation of normal adult human osteoblast-like cells in vitro. Bone. 1994;15:307–11.

    Article  CAS  PubMed  Google Scholar 

  27. Verhaar HJ, Damen CA, Duursma SA, et al. Comparison of the action of 17β-estradiol and progestins with insulin-like growth factors-I/-II and TGF-β-1 on the growth of normal adult human bone forming cells. Maturitas. 1995;21:237–43.

    Article  CAS  PubMed  Google Scholar 

  28. Lau KH, Wang SP, Linkhart TA, et al. Picomolar norethindrone in vitro stimulates the cell proliferation and activity of a human osteosarcoma cell line and increases bone collagen synthesis without an effect on bone resorption. J Bone Miner Res. 1994;9:695–704.

    Article  CAS  PubMed  Google Scholar 

  29. Chen L, Scholler J, Foged NT. Effects of progesterone on proliferation and differentiation of fetal rat calvarial osteoblasts in vitro. Zhonghua Fu Chan Ke Za Zhi. 1997;32:538–40.

    CAS  PubMed  Google Scholar 

  30. Thijssen JHH. Overview on the effects of progestins on bone. Maturitas. 2003;46(S1):S77–87.

    Article  CAS  PubMed  Google Scholar 

  31. Eleftheriades MI, Lambrinoudaki IV, Christodoulakos GE, Gregoriou OV, Economou EV, Kouskouni EE, Antoniou AG, Perrea DN, Dontas IA, Raptou PD, Lyritis GP, Creatsas GC. Effect of oral contraceptive treatment on bone mass acquisition in skeletally immature young female rats. Contraception. 2005;71:362–71.

    Article  CAS  PubMed  Google Scholar 

  32. Register TC, Jayo MJ, Jerome CP. Oral contraceptive treatment inhibits the normal acquisition of bone mineral in skeletally immature young adult female monkeys. Osteoporos Int. 1997;7:348–53.

    Article  CAS  PubMed  Google Scholar 

  33. Hosking DJ, MR MC, Ravn P, Wasnich RD, Thompson OE, Dalev MS, Yates AJ, for the EPIC Study Group. Alendronate in the prevention of osteoporosis: EPIC study two-year results. J Bone Min Res. 1996;11(S1):133.

    Google Scholar 

  34. Naessen T, Olsson SE, Gudmundson J. Differential effects on bone density of progestogen-only methods for contraception in premenopausal women. Contraception. 1995;52:35–9.

    Article  CAS  PubMed  Google Scholar 

  35. Gargano V, Massaro M, Morra I, Formisano C, Di Carlo C, Nappi C. Effects of two low-dose combined oral contraceptives containing drospirenone on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study. Contraception. 2008;78:10–5.

    Google Scholar 

  36. Liu SL, Lebrun CM. Effect of oral contraceptives and hormone replacement therapy on bone mineral density in premenopausal and perimenopausal women: a systematic review. Br J Sports Med. 2006;40:11–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lopez LM, Grimes DA, Schulz KF, Curtis KM, Chen M. Steroidal contraceptives: effect on bone fractures in women (Review). Cochrane Library. 2014;(6)

    Google Scholar 

  38. Cromer BA. Bone mineral density in adolescent and young adult women on injectable or oral contraception. Bone mineral density in adolescent and young adult women on injectable or oral contraception. Curr Opin Obstet Gynecol. 2003;15:353–7. Erratum in: Curr Opin Obstet Gynecol. 2003 Dec;15(6):543

    Article  PubMed  Google Scholar 

  39. Cooper C, Hannaford P, Croft P, Kay CR. Oral contraceptive pill use and fractures in women: a prospective study. Bone. 1993;14:41–5.

    Article  CAS  PubMed  Google Scholar 

  40. Vessey M, Mant J, Painter R. Oral contraception and other factors in relation to hospital referral for fracture. Findings in a large cohort study. Contraception. 1998;57:231–5.

    Article  CAS  PubMed  Google Scholar 

  41. Mallmin H, Ljunghall S, Persson I, Bergström R. Risk factors for fractures of the distal forearm: a population-based case-control study. Osteop Int. 1994;4:298–304.

    Article  CAS  Google Scholar 

  42. Lopez LM, Chen M, Mullins Long S, Curtis KM, Helmerhorst FM. Steroidal contraceptives and bone fractures in women: evidence from observational studies. Cochrane Database Syst Rev. 2015;(7):CD009849.

    Google Scholar 

  43. Memon S, Iversen L, Hannaford PC. Is the oral contraceptive pill associated with fracture in later life? New evidence from the Royal College of General Practitioners Oral Contraception Study. Contraception. 2011;84(1):40–7.

    Article  CAS  PubMed  Google Scholar 

  44. Barad D, Kooperberg C, Wactawski-Wende J, Liu J, Hendrix SL, Watts NB. Prior oral contraception and postmenopausal fracture: a Women‘s Health Initiative observational cohort study. Fertil Steril. 2005;84:374–83.

    Article  PubMed  Google Scholar 

  45. Meier C, Brauchli YB, Jick SS, Kraenzlin ME, Meier CR. Use of depot medroxyprogesterone acetate and fracture risk. J Clin Endocrinol Metab. 2010;95:4909–16.

    Article  CAS  PubMed  Google Scholar 

  46. Vestergaard P, Rejnmark L, Mosekilde L. Oral contraceptive use and risk of fractures. Contraception. 2006;73(6):571–6.

    Article  CAS  PubMed  Google Scholar 

  47. Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk in very young women using combined oral contraceptives. Contraception. 2008a;78(5):358–64.

    Article  CAS  PubMed  Google Scholar 

  48. Dombrowski M, Jacob L, Hadji P, Kostev K. Oral contraceptive use and fracture risk—a retrospective study of 12,970 women in the UK. Osteop Int. 2017;28:2349–55.

    Article  CAS  Google Scholar 

  49. Pasco JA, Kotowicz MA, Henry MJ, Panahi S, Seeman E, Nicholson GC. Oral contraceptives and bone mineral density: a population-based study. Am J Obstet Gynecol. 2000;182:265–9.

    Article  CAS  PubMed  Google Scholar 

  50. Petitti DB, Piaggio G, Mehta S, Cravioto MC, Meirik O. for the who study of hormonal contraception and bone health Steroid hormone contraception and bone mineral density: a cross-sectional study in an international population. The WHO Study of Hormonal Contraception and Bone Health. Obstet Gynecol. 2000;95:736–44.

    CAS  PubMed  Google Scholar 

  51. Gambacciani M, Cappagli B, Lazzarini V, Ciaponi M, Fruzzetti F, Genazzani AR. Longitudinal evaluation of perimenopausal bone loss: effects of different low dose oral contraceptive preparations on bone mineral density. Maturitas. 2006;54:176–80.

    Article  CAS  PubMed  Google Scholar 

  52. Hartard M, Kleinmond C, Luppa P, Zelger O, Egger K, Wisemann M, Weissenbacher ER, Erben RG. Comparison of the skeletal effects of the progestogens desogestrel and levonorgestrel in oral contraceptive preparations in young women: controlled, open, partly randomized investigation over 13 cycles. Contraception. 2006;74:367–75.

    Article  CAS  PubMed  Google Scholar 

  53. Pikkarainen E, Lehtonen-Veromaa M, Möttönen T, Kautiainen H, Viikari J. Estrogen-progestin contraceptive use during adolescence prevents bone mass acquisition: a 4-year follow-up study. Contraception. 2008;78:226–31.

    Article  CAS  PubMed  Google Scholar 

  54. Allali F, El Mansouri L, Abourazzak F, Ichchou L, Khazzani H, Bennani L, Abouqal R, Hajjaj-Hassouni N. The effect of past use of oral contraceptive on bone mineral density, bone biochemical markers and muscle strength in healthy pre- and post-menopausal wo-men. BMC Womens Health. 2009;9:31–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Scholes D, Ichikawa L, LaCroix AZ, Spangler L, Beasley J, Reed S, Ott SM. Oral contraceptive use and bone density in adolescent and young adult women. Contraception. 2010;81:35–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wei S, Jones G, Thomson R, Dwyer T, Venn A. Oral contraceptive use and bone mass in women aged 26–36 years. Osteoporos Int. 2011;22:351–5.

    Article  CAS  PubMed  Google Scholar 

  57. Polatti F, Perotti F, Filippa N, Gallina D, Nappi RE. Bone mass and long-term monophasic oral contraceptive treatment in young women. Contraception. 1995;51:221–4.

    Article  CAS  PubMed  Google Scholar 

  58. La Vecchia C, Tavani A, Gallus S. Oral contraceptives and risk of hip fractures. Lancet. 1999;354:335–6.

    Article  PubMed  Google Scholar 

  59. Berenson AB, Breitkopf CR, Grady JJ, Rickert VI, Thomas A. Effects of hormonal contraception on bone mineral density after 24 months of use. Obstet Gynecol. 2004;103:899–906.

    Article  CAS  PubMed  Google Scholar 

  60. Foth DT, Römer T, Ahrendt H-J. Hormonelle Kontrazeption mit östradiol-haltigen Kombinationspräparaten. Gynäkol Endokrinol. 2013;11:162–7.

    Article  CAS  Google Scholar 

  61. Fruzzetti F, Trémollieres F, Bitzer J. An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate/dienogest. Gynecol Endocrinol. 2012;28(5):400–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Mansour D, Verhoeven C, Sommer W, Weisberg E, Taneepanichskul S, Melis GB, Sundstroem-Poromaa I, Korver T. Efficacy and tolerability of a monophasic combined oral contraceptive containing nomegestrol acetate and 17 β -oestradiol in a 24/4 regimen, in comparison to an oral contraceptive containing ethinylestradiol and drospirenone in a 21/7 regimen. Eur J Contracept Reprod Health Care. 2011;16:430–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Endrikat J, Mih E, Dusterberg B, Land K, Gerlinger C, Schmidt W, Felsenberg D. A 3-year double-blind, randomized, controlled study on the influence of two oral contraceptives containing either 20 μg or 30 μg ethinylestradiol in combination with levonorgestrel on bone mineral density. Contraception. 2004;69:179–87.

    Article  CAS  PubMed  Google Scholar 

  64. Nappi C, Di Spiezio SA, Acunzo G, Bifulco G, Tommaselli GA, Guida M, Di Carlo C. Effects of a low-dose and ultra-low-dose combined oral contraceptive use on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study. Contraception. 2003;67:355–9.

    Article  CAS  PubMed  Google Scholar 

  65. Paoletti AM, Orru M, Floris S, Mannias M, Vacca AMB, Ajossa S, Guerriero S, Melis GB. Evidence that treatment with monophasic oral contraceptive formulations containing ethinylestradiol plus gestodene reduces bone resorption in young women. Contraception. 2000;61:259–63.

    Article  CAS  PubMed  Google Scholar 

  66. Cromer BA, Stager M, Bonny A, Lazebnik R, Rome E, Ziegler J, Debanne SM. Depot medroxyprogesterone acetate, oral contraceptives and bone mineral density in a cohort of adolescent girls. J Adolesc Health. 2004;2004(35):434–41.

    Article  Google Scholar 

  67. Almstedt HC, Cook MM, Bramble LF, Dabir DV, LaBrie JW. Oral contraceptive use, bone mineral density, and bone turnover markers over 12 months in college-aged females. J Bone Miner Metab. 2020;38:544–54.

    Article  CAS  PubMed  Google Scholar 

  68. Goshtasebi A, Brajic S, Delia Scholes D, Lederer Goldberg TB, Berenson A, Prior JC. Adolescent use of combined hormonal contraception and peak bone mineral density accrual: a meta-analysis of international prospective controlled studies. Clin Endocrinol. 2019;90:517–24.

    Article  CAS  Google Scholar 

  69. Rizzo AC, Goldberg TB, Biason TB, Kurokawa CS, Silva CC, Corrente JE, Nunes HRC. One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives. J Pediatr. 2019;95:567–74.

    Article  Google Scholar 

  70. Brajic TS, Berger C, Schlammerl K, Macdonald H, Kalyan S, Hanley DA, Adachi JD, Kovacs CS, Prior JC, The CaMos Research Group. Combined hormonal contraceptives use and bone mineral density changes in adolescent and young women in a prospective population-based Canada-wide observational study. J Musculoskelet Neuronal Interact. 2017;18(2):227–36.

    Google Scholar 

  71. Gersten J, Hsieh J, Weiss H, Ricciotti MA. Effect of extended 30 μg ethinyl estradiol with continuous low-dose ethinyl estradiol and cyclic 20 μg ethinyl estradiol oral contraception on adolescent bone density: a randomized trial. J Pediatr Adolesc Gynecol. 2016;29(6):635–542.

    Article  PubMed  Google Scholar 

  72. Berenson AB, Rahman M, Breitkopf CR, Bi LX. Effects of depot medroxyprogesterone acetate and 20 μg oral contraceptives on bone mineral density. Obstet Gynecol. 2008;112(4):788.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Gai L, Jia Y, Zhang M, Gai P, Wang S, Shi H, Yu X, Liu Y. Effect of two kinds of different combined oral contraceptives use on bone mineral density in adolescent women. Contraception. 2012;86(4):332–6.

    Article  CAS  PubMed  Google Scholar 

  74. Biason TP, Goldberg T, Kurokawa CS, Moretto MR, Teixeira AS, de Carvalho Nunes HR. Low-dose combined oral contraceptive use is associated with lower bone mineral content variation in adolescents over a 1-year period. BMC Endocr Disord. 2015;15(1):15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Lattakova M, Borovsky M, Payer J, Killinger Z. Oral contraception usage in relation to bone mineral density and bone turnover in adolescent girls. Eur J Contracept Reprod Health Care Volume. 2009;14(3):207–14.

    Article  CAS  Google Scholar 

  76. Scholes D, Hubbard RA, Ichikawa LE, LaCroix AZ, Spangler L, Beasley JM, Reed SM, Ott SM. Oral contraceptive use and bone density change in adolescent and young adult women: a prospective study of age, hormone dose, and discontinuation. J Clin Endocrinol Metab. 2011;96(9):E1380–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lara-Torre E, Edwards CP, Perlman S, Hertweck SP. Bone mineral density in adolescent females using depot medroxyprogesterone acetate. J Pediatr Adolesc Gynecol. 2004;17(1):17–21.

    Article  PubMed  Google Scholar 

  78. Cromer BA, Stager M, Bonny A, Lazebnik R, Rome E, Ziegler J, Debanne SM. Depot medroxyprogesterone acetate, oral contraceptives and bone mineral density in a cohort of adolescent girls. J Adolesc Health. 2004;35:434–41.

    Article  PubMed  Google Scholar 

  79. Birkhaeuser M, Hadji P, Mueck AO, Neulen J, Thaler C, Wiegratz I, Wildt L. Zuercher Gesprächskreis. Kontrazept Knochen Frauenarzt. 2013;54:34–40.

    Google Scholar 

  80. Polatti F, Perotti F, Filippa N, Galina D, Nappi RE. Bone mass and long-term monophasic oral contraceptive treatment in young women. Contraception. 1995;51:221–4.

    Google Scholar 

  81. Gordon CM, Zemel BS, Wren TAL, Leonard MB, Bachrach LK, Rauch F, Gilsanz V, Rosen CJ, Winer KK. The determinants of peak bone mass. (downloaded June 16th, 2020).

    Google Scholar 

  82. Massai R, Mäkäräinen L, Kuukankorpi A, Klipping C, Duijkers I, Dieben T. The combined contraceptive vaginal ring and bone mineral density in healthy pre-menopausal women. Hum Reprod. 2005;20:2764–8.

    Article  CAS  PubMed  Google Scholar 

  83. Massaro M, Di Carlo C, Gargan V, Formisano C, Bifulco G, Nappi C. Effects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: a prospective, con-trolled, randomized study. Contraception. 2010;81:209–14.

    Article  CAS  PubMed  Google Scholar 

  84. Rice CF, Killick SR, Dieben T, Coelingh BH. A comparison of the inhibition of ovulation achieved by desogestrel 75 micrograms and levonorgestrel 30 micrograms daily. Hum Reprod. 1999;14(4):982–5.

    Article  CAS  PubMed  Google Scholar 

  85. Bahamondes L, Monteiro-Dantas C, Espejo-Arce X, et al. A prospective study of the forearm bone density of users of etonogestrel- and levonorgestrel-releasing contraceptive implants. Hum Reprod. 2006;21:466–70.

    Article  CAS  PubMed  Google Scholar 

  86. Pongsatha S, Ekmahachai M, Suntornlimsiri N, Morakote N, Chaovisitsaree S. Bone mineral density in women using the subdermal contraceptive implant Implanon for at least 2 years. Int J Gynecol Obstet. 2010;109:223–5.

    Article  CAS  Google Scholar 

  87. Di X, Li Y, Zhang C, Jiang J, Gu S. Effects of levonorgestrel-releasing subdermal contraceptive implants on bone density and bone metabolism. Contraception. 1999;60:161–6.

    Article  CAS  PubMed  Google Scholar 

  88. Cromer BA, Blair JM, Mahan JD, Zibners L, Naumovski Z. A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant), or oral contraceptives. J Pediatr. 1996;129(5):671–6.

    Google Scholar 

  89. Vestergaard P, Rejnmark L, Mosekilde L. The effects of depot medroxyprogesterone acetate and intrauterine device use on fracture risk in Danish women. Contraception. 2008b;78(6):459–64.

    Article  CAS  PubMed  Google Scholar 

  90. Johnson CC, Burkman RT, Gold MA, Brown RT, Harel Z, Bruner A, Stager M, Bachrach LK, Hertweck SP, Nelson AL, Nelson DA, Coupey SM, McLeod A, Bone HG. Longitudinal study of depot medroxyprogesterone acetate (Depo-Provera) effects on bone health in adolescents: study design, population characteristics and base-line bone mineral density. Contraception. 2008;77:239–48.

    Article  CAS  PubMed  Google Scholar 

  91. Kyvernitakis I, Kostev K, Nassour T, Thomasius F, Hadji P. The impact of depot medroxyprogesterone acetate on fracture risk: a case-control study from the UK. Osteop Int. 2017;28:291–7.

    Article  CAS  Google Scholar 

  92. Beksinska ME, Smit JA. Hormonal contraception and bone mineral density. Exp Rev Obstet Gynecol. 6(3):305–19.

    Google Scholar 

  93. Berenson AB, Radecki CM, Grady JJ, et al. A prospective, controlled study of the effects of hormonal contraception on bone mineral density. Obstet Gynecol. 2001;98:576–82.

    Google Scholar 

  94. Kaunitz AM, Miller PD, Rice VM, Ross D, McClung MR. Bone mineral density in women aged 25–35 years receiving depot medroxyprogesterone acetate: recovery following discontinuation. Contraception. 2006;74:90–9.

    Article  CAS  PubMed  Google Scholar 

  95. Harel Z, Johnson CC, Gold MA, Cromer B, Peterson E, Burkman R, Stager M, Brown R, Bruner A, Coupey SM, Hertweck SP, Bone GH, Wolter K, Nelson AL, Marshall S, Bachrach BK. Recovery of bone mineral density in adolescents following the use of depot medroxyprogesterone acetate contraceptive injections. Contraception. 2010;81(4):281–91.

    Article  CAS  PubMed  Google Scholar 

  96. Kaunitz AM. Presented at the 7th World Congress on Controversies in Obstetrics and Gynecology and Infertility Athens, Greece, from April 14, 2005.

    Google Scholar 

  97. Kaunitz AM, Darney PD, Ross D, Wolter KD, Speroff L. Subcutaneous DMPA vs. intramuscular DMPA: a 2-year randomized study of contraceptive efficacy and bone mineral density. Contraception. 2009;80:7–17.

    Article  CAS  PubMed  Google Scholar 

  98. Guilbert ER, Brown JP, Kaunitz AM, Wagner MS, Bérubé J, Charbonneau L, Francoeur D, Gilbert A, Roy G, Senikas V, Jacob R, Morin R. The use of depot-medroxyprogesterone acetate in contraception and its potential impact on skeletal health. Contraception. 2009;79:167–77.

    Article  CAS  PubMed  Google Scholar 

  99. Cromer BA. Bone mineral density in adolescent and young adult women on injectable or oral contraception. Curr Opin Obstet Gynecol. 2003;15:353–7.

    Article  PubMed  Google Scholar 

  100. Edwards CP, Hertweck SP, Perlman SE, et al. A prospective study evaluating the effects of Depo Provera on bone mineral density in adolescent females: a preliminary report [abstract]. J Pediat Adol Gynecol. 1998;11:201.

    Article  Google Scholar 

  101. Busen NH, Britt RB, Rianon N. Bone mineral density in a cohort of adolescent women using depot medroxyprogesterone acetate for one to two years. J Adolesc Health. 2003;32:257–9.

    Article  PubMed  Google Scholar 

  102. Cromer BA, McArdle Blair J, Mahan JD, Zibners L, Naumovski Z. A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant), or oral contraceptives. J Pediatr. 1996;129:671–6.

    Article  CAS  PubMed  Google Scholar 

  103. Cundy T, Ames R, Horne A, Clearwater J, Roberts H, Gamble G, Reid IR. A randomized controlled trial of estrogen replacement therapy in long-term users of depot medroxyprogesterone acetate. J Clin Endocrinol Metab. 2003;88:78–81.

    Article  CAS  PubMed  Google Scholar 

  104. Cromer BA, Bonny AE, Stager M, Lazebnik R, Rome E, Ziegler J, Camlin-Shingler K. Secic. Bone mineral density in adolescent females using injectable or oral contraceptives: a 24-month prospective study. Fertil Steril. 2008;90(6):2060–7.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Dennison E, Cole Z, Cooper C. Diagnosis and epidemiology of osteoporosis. Curr Opin Rheumatol. 2005;17:456–61.

    Article  PubMed  Google Scholar 

  106. Carr BR, Breslau NA, Peng N, Adams-Huet B, Bradshaw KD, Steinkampf MP. Effect of gonadotropin-releasing hormone agonist and medroxyprogesterone acetate on calcium metabolism: a prospective, randomized, double-blind, placebo-controlled, crossover trial. Fertil Steril. 2003;80:1216–23.

    Article  PubMed  Google Scholar 

  107. Pinter B, Kocijancic A, Marc J, Andolsek-Jeras L, Prezelj J. Vitamin D receptor gene polymorphism and bone metabolism during low-dose oral contraceptive use in young women. Contraception. 2003;67:33–7.

    Article  CAS  PubMed  Google Scholar 

  108. Clark MK, Sowers M, Levy BT, et al. Magnitude and variability of sequential estradiol and progesterone concentrations in women using depot medroxyprogesterone acetate for contraception. Fertil Steril. 2001;75:871–7.

    Article  CAS  PubMed  Google Scholar 

  109. Curtis KM, Martins SL. Progestogen-only contraception and bone mineral density: a systematic review. Contraception. 2006;73:470–87.

    Article  CAS  PubMed  Google Scholar 

  110. Speroff L, Glass R, Kase N. Clinical gynecologic endocrinology and infertility. Baltimore, MD: Williams & Wilkins; 1994.

    Google Scholar 

  111. Cromer BA, Lazebnik R, Rome E, Stager M, Bonny A, Ziegler J, et al. Double-blinded randomized controlled trial of estrogen supplementation in adolescent girls who receive depot medroxyprogesterone acetate for contraception. Am J Obstet Gynecol. 2005;192:42–7.

    Article  CAS  PubMed  Google Scholar 

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Birkhaeuser, M. (2021). Hormonal Contraception and Bone. In: Meriggiola, M.C., Gemzell-Danielsson, K. (eds) Female and Male Contraception. Trends in Andrology and Sexual Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-70932-7_21

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