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Impact of hormone therapy on the bone density of women with premature ovarian insufficiency: A systematic review

  • Giulia Paiva Oliveira Costa
    Affiliations
    Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, Room 10166, Cerqueira Cesar, Sao Paulo, SP 05403-000, Brazil
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  • Edson Santos Ferreira-Filho
    Affiliations
    Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, Room 10166, Cerqueira Cesar, Sao Paulo, SP 05403-000, Brazil
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  • Ricardo dos Santos Simoes
    Affiliations
    Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, Room 10166, Cerqueira Cesar, Sao Paulo, SP 05403-000, Brazil
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  • José Maria Soares-Junior
    Affiliations
    Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, Room 10166, Cerqueira Cesar, Sao Paulo, SP 05403-000, Brazil
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  • Edmund Chada Baracat
    Affiliations
    Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, Room 10166, Cerqueira Cesar, Sao Paulo, SP 05403-000, Brazil
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  • Gustavo Arantes Rosa Maciel
    Correspondence
    Corresponding author at: Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
    Affiliations
    Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, Room 10166, Cerqueira Cesar, Sao Paulo, SP 05403-000, Brazil
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      Highlights

      • Women with premature ovarian insufficiency tend to have lower bone mineral density.
      • Hormone therapy can improve the bone health of women with premature ovarian insufficiency.
      • Delay in the diagnosis can negatively influence treatment effectiveness in maintaining bone mass or restoring it to the normal range.
      • Higher doses of estrogen, with at least 2 mg estradiol or 1.25 mg conjugated equine estrogens, could better prevent bone loss in this population.

      Abstract

      Introduction

      Women with premature ovarian insufficiency (POI) are exposed to a long period of estrogenic deficiency, which potentially brings higher health risks, especially regarding bone health. We performed a systematic review of the literature to evaluate the effect of hormone therapy (HT) on bone mineral density (BMD) in women with POI.

      Materials and methods

      A systematic search was performed of the MEDLINE and EMBASE databases up to September 2021. We included studies that analyzed women with idiopathic (spontaneous) POI treated with HT, and those who had BMD evaluated. Analysis of risk of bias of studies selected was performed.

      Results

      We found 335 articles and selected 16 studies according to the inclusion criteria. Most of the studies revealed lower bone density in both the femoral neck and lumbar spine of women with POI compared with healthy women. Bone mass had the tendency to remain stable in women treated with estrogen + progestin therapy. However, in women already with bone mass loss, the therapy - in the doses most frequently used - was not able to revert the loss. Higher doses of estrogen seem to have a positive impact on BMD, as did combined oral contraceptives used continuously. Also, the interruption of HT for longer than one year was linked to significant bone loss.

      Conclusion

      Although HT brings clear benefits, further studies are needed to establish its long-term effects, as well as doses and formulations with better protective effects on the bone mass of these women.

      Abbreviations:

      POI (premature ovarian insufficiency), HT (hormone therapy), BMD (bone mineral density), CEE (conjugated equine estrogens), EE (ethinylestradiol), COC (combined oral contraceptive)

      Keywords

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      References

        • Webber L.
        • Davies M.
        • Anderson R.
        • Bartlett J.
        • Braat D.
        • Cartwright B.
        • Cifkova R.
        • de Muinck Keizer-Schrama S.
        • Hogervorst E.
        • Janse F.
        • Liao L.
        • Vlaisavljevic V.
        • Zillikens C.
        • Vermeulen N.
        ESHRE guideline: management of women with premature ovarian insufficiency.
        Hum. Reprod. 2016; 31: 926-937https://doi.org/10.1093/humrep/dew027
        • Nelson L.M.
        Clinical practice. Primary ovarian insufficiency.
        N. Engl. J. Med. 2009; 360: 606-614https://doi.org/10.1056/NEJMcp0808697
        • Kok H.S.
        • van Asselt K.M.
        • van der Schouw Y.T.
        • van der Tweel I.
        • Peeters P.H.M.
        • Wilson P.W.F.
        • Pearson P.L.
        • Grobbee D.E.
        Heart disease risk determines menopausal age rather than the reverse.
        J. Am. Coll. Cardiol. 2006; 47: 1976-1983https://doi.org/10.1016/j.jacc.2005.12.066
        • Committee Opinion No. 698
        Hormone therapy in primary ovarian insufficiency.
        Obstet. Gynecol. 2017; 129: e134-e141https://doi.org/10.1097/AOG.0000000000002044
        • Davies J.H.
        • Evans B.A.J.
        • Gregory J.W.
        Bone mass acquisition in healthy children. 2005: 373-379https://doi.org/10.1136/adc.2004.053553
        • Cartwright B.
        • Robinson J.
        • Seed P.T.
        • Fogelman I.
        • Rymer J.
        Hormone replacement therapy versus the combined oral contraceptive pill in premature ovarian failure: a randomized controlled trial of the effects on bone mineral density.
        J. Clin. Endocrinol. Metab. 2016; 101: 3497-3505https://doi.org/10.1210/jc.2015-4063
        • Popat V.B.
        • Calis K.A.
        • Kalantaridou S.N.
        • Vanderhoof V.H.
        • Koziol D.
        • Troendle J.F.
        • Reynolds J.C.
        • Nelson L.M.
        Bone mineral density in young women with primary ovarian insufficiency: results of a three-year randomized controlled trial of physiological transdermal estradiol and testosterone replacement.
        J. Clin. Endocrinol. Metab. 2014; 99: 3418-3426https://doi.org/10.1210/jc.2013-4145
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        BMJ. 2009; 339: 332-336https://doi.org/10.1136/bmj.b2535
        • Higgins J.P.T.
        • Altman D.G.
        • Gøtzsche P.C.
        • Jüni P.
        • Moher D.
        • Oxman A.D.
        • Savović J.
        • Schulz K.F.
        • Weeks L.
        • Sterne J.A.C.
        The Cochrane collaboration's tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343: 1-9https://doi.org/10.1136/bmj.d5928
        • Wells P.T.G.A.
        • Shea B.
        • O’Connell D.
        • Peterson J.
        • Welch V.
        • Losos M.
        The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomized Studies in Meta-analyses.
        Ottawa Hosp. Res. Institute, 2014
        • Luchini C.
        • Stubbs B.
        • Solmi M.
        • Veronese N.
        Assessing the quality of studies in meta-analyses: advantages and limitations of the Newcastle Ottawa scale.
        World J. Meta-Anal. 2017; 5: 80https://doi.org/10.13105/wjma.v5.i4.80
        • Gao B.
        • Dwivedi S.
        • Milewski M.D.
        • Cruz Jr., A.I.
        Chronic lack of sleep is associated with increased sports injury in adolescents: a systematic review and meta-analysis.
        Orthop. J. Sport. Med. 2019; 7 (2325967119S00132)https://doi.org/10.1177/2325967119S00132
        • Han J.
        • Guo X.
        • Yu X.
        • Liu S.
        • Cui X.
        • Zhang B.
        • Liang H.
        25-hydroxyvitamin D and Total cancer incidence and mortality: a meta-analysis of prospective cohort studies.
        Nutrients. 2019; 11: 2295https://doi.org/10.3390/nu11102295
        • Mittal M.
        • Kreatsa M.
        • Narvekar N.
        • Savvas M.
        • Hamoda H.
        Fertility desires, choice of hormone replacement and the effect of length of time since menopause on bone density in women with premature ovarian insufficiency: a review of 223 consecutive new referrals to a tertiary centre., post.
        Reprod. Heal. 2014; 20: 104-111https://doi.org/10.1177/2053369114539151
        • Amarante F.
        • Vilodre L.C.
        • Maturana M.A.
        • Spritzer P.M.
        Women with primary ovarian insufficiency have lower bone mineral density.
        Braz. J. Med. Biol. Res. 2011; 44: 78-83
        • Crofton P.M.
        • Evans N.
        • Bath L.E.
        • Warner P.
        • Whitehead T.J.
        • Critchley H.O.D.
        • Kelnar C.J.H.
        • Wallace W.H.B.
        Physiological versus standard sex steroid replacement in young women with premature ovarian failure: effects on bone mass acquisition and turnover.
        Clin. Endocrinol. 2010; 73: 707-714https://doi.org/10.1111/j.1365-2265.2010.03868.x
        • Lana M.B.P.
        • Straminsky V.
        • Onetto C.
        • Amuchastegui J.M.
        • Blanco G.
        • Galluzzo L.
        • Provenzano S.
        • Nolting M.
        What is really responsible for bone loss in spontaneous premature ovarian failure? A new enigma.
        Gynecol. Endocrinol. 2010; 26: 755-759https://doi.org/10.3109/09513590.2010.487599
        • Podfigurna A.
        • Maciejewska-Jeske M.
        • Nadolna M.
        • Mikolajska-Ptas P.
        • Szeliga A.
        • Bilinski P.
        • Napierala P.
        • Meczekalski B.
        Impact of hormonal replacement therapy on bone mineral density in premature ovarian insufficiency patients.
        J. Clin. Med. 2020; 9https://doi.org/10.3390/jcm9123961
        • Gazarra L.B.C.
        • Bonacordi C.L.
        • Yela D.A.
        • Benetti-Pinto C.L.
        Bone mass in women with premature ovarian insufficiency: a comparative study between hormone therapy and combined oral contraceptives.
        Menopause. 2020; 27: 1110-1116https://doi.org/10.1097/GME.0000000000001592
        • Popat V.B.
        • Calis K.A.
        • Vanderhoof V.H.
        • Cizza G.
        • Reynolds J.C.
        • Sebring N.
        • Troendle J.F.
        • Nelson L.M.
        Bone mineral density in estrogen-deficient young women.
        J. Clin. Endocrinol. Metab. 2009; 94: 2277-2283https://doi.org/10.1210/jc.2008-1878
        • Uygur D.
        • Sengul O.
        • Bayar D.
        • Erdinc S.
        • Batioglu S.
        • Mollamahmutoglu L.
        Bone loss in young women with premature ovarian failure.
        Arch. Gynecol. Obstet. 2005; 273: 17-19https://doi.org/10.1007/s00404-005-0029-7
        • Metka M.
        • Holzer G.
        • Heytmanek G.
        • Huber J.
        Hypergonadotropic hypogonadic amenorrhea (World Health Organization III) and osteoporosis.
        Fertil. Steril. 1992; 57: 37-41
        • Gökmen O.
        • Seçkin N.C.
        • Sener A.B.
        • Ozakşit G.
        • Ekmekçi S.
        A study of premature ovarian failure in Turkish women.
        Gynecol. Endocrinol. Off. J. Int. Soc. Gynecol. Endocrinol. 1995; 9: 283-287https://doi.org/10.3109/09513599509160460
        • Kanj R.V.
        • Ofei-Tenkorang N.A.
        • Altaye M.
        • Gordon C.M.
        Evaluation and management of primary ovarian insufficiency in adolescents and young adults.
        J. Pediatr. Adolesc. Gynecol. 2018; 31: 13-18https://doi.org/10.1016/j.jpag.2017.07.005
        • Giraldo H.
        • Benetti-Pinto C.
        • Ferreira V.
        • Garmes H.
        • Yela D.
        • Giraldo P.
        Standard hormone therapy is inadequate for bone density in premature ovarian insufficiency.
        Gynecol. Endocrinol. 2017; 33: 283-286https://doi.org/10.1080/09513590.2016.1257602
        • Bachelot A.
        • Nicolas C.
        • Gricourt S.
        • Dulon J.
        • Leban M.
        • Golmard J.L.
        • Touraine P.
        Poor compliance to hormone therapy and decreased bone mineral density in women with premature ovarian insufficiency.
        PLoS One. 2016; 11e0164638https://doi.org/10.1371/journal.pone.0164638
        • Benetti-Pinto C.L.
        • Ferreira V.B.
        • Yela D.A.
        Long-term follow-up of bone density in women with primary ovarian insufficiency.
        Menopause. 2015; 22: 946-949https://doi.org/10.1097/GME.0000000000000445
        • Tella S.H.
        • Gallagher J.C.
        Prevention and treatment of postmenopausal osteoporosis.
        J. Steroid Biochem. Mol. Biol. 2014; 142: 155-170https://doi.org/10.1016/j.jsbmb.2013.09.008
        • Blake G.M.
        • Fogelman I.
        The role of DXA bone density scans in the diagnosis and treatment of osteoporosis.
        Postgrad. Med. J. 2007; 83: 509-517https://doi.org/10.1136/pgmj.2007.057505
        • Rossouw J.E.
        • Anderson G.L.
        • Prentice R.L.
        • LaCroix A.Z.
        • Kooperberg C.
        • Stefanick M.L.
        • Jackson R.D.
        • Beresford S.A.A.
        • Howard B.V.
        • Johnson K.C.
        • Kotchen J.M.
        • Ockene J.
        • Trial R.C.
        Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women's health initiative randomized controlled trial.
        JAMA. 2002; 288: 321-333
        • Rossouw J.E.
        • Prentice R.L.
        • Manson J.E.
        • Wu L.
        • Barad D.
        • Barnabei V.M.
        • Ko M.
        • Lacroix A.Z.
        • Margolis K.L.
        • Stefanick M.L.
        Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause.
        J. Am. Med. Assoc. 2007; 297: 1465-1477https://doi.org/10.1001/jama.297.13.1465
        • Webber L.
        • Anderson R.A.
        • Davies M.
        • Janse F.
        • Vermeulen N.
        HRT for women with premature ovarian insufficiency: a comprehensive review.
        Hum. Reprod. Open. 2017; 2017hox007https://doi.org/10.1093/hropen/hox007
        • Goswami D.
        • Conway G.S.
        Premature ovarian failure.
        Hum. Reprod. Update. 2005; 11: 391-410https://doi.org/10.1093/humupd/dmi012
        • Lambrinoudaki I.
        • Paschou S.A.
        • Lumsden M.A.
        • Faubion S.
        • Makrakis E.
        • Kalantaridou S.
        • Panay N.
        Premature ovarian insufficiency: a toolkit for the primary care physician.
        Maturitas. 2021; 147: 53-63https://doi.org/10.1016/j.maturitas.2020.11.004
        • Panay N.
        • Anderson R.A.
        • Nappi R.E.
        • Vincent A.J.
        • Vujovic S.
        • Webber L.
        • Wolfman W.
        Premature ovarian insufficiency: an international menopause society white paper.
        Climacteric. 2020; 23: 426-446https://doi.org/10.1080/13697137.2020.1804547