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Hormone Replacement Therapy in Premature Ovarian Insufficiency

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Menstrual Cycle Related Disorders

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Abstract

Early loss of ovarian function can present insidiously with occasional periods of recovery. This occurs in the great majority of cases, and it should be identified as premature ovarian insufficiency (POI). Cases with sudden, definitive onset (due to bilateral ovariectomy or treatments usually related to oncological conditions) should be considered premature ovarian failure (POF). Therapy aims at treating hormone deficits and other underlying causes. POI symptoms include the classic short-term ones (vasomotor symptoms, insomnia, joint pain, mood changes, low energy and low libido, impaired memory, and concentration difficulties) as well as various repercussions on the lower genital tract, the cardiovascular system, bone mass (osteopenia, osteoporosis, increased fracture risk, arthrosis), cognitive function (cognitive dysfunction, especially memory and concentration problems, plus increased risk of dementia), mood, and loss of reproductive capacity.

The two main lines of treatment are so-called physiological sex steroid replacement (pSSR), involving administration of transdermal E2 (100–200 mcg) together with micronized natural progesterone in women who still have their uterus, and standard hormone replacement therapy (sHRT), comprising ECE + progestin and combined hormone contraceptive. Another good choice for both adult POI patients and adolescents who want to avoid pregnancy is a progestogen intrauterine device (IUD) combined with continuous 17β-estradiol (transdermal or oral). Treatment should be started as early as possible, and pSSR is the preferred first-line treatment given its favorable metabolic profile and influence on bone mass. Dosage should be individually tailored, depending on patient age. Younger patients who experience POI soon after menarche and have not achieved peak bone mass require adequate dosages (see the protocols for hypergonadotropic primary amenorrhea). Therapy must always be accompanied by good lifestyle and adequate intake of calcium and vitamin D. Patients can use a combined hormone contraceptive if there are no contraindications. This usually has a positive psychological impact on adolescents, but it does not exercise any substantial effect on acquisition of or increase in peak bone mass. Treatment must be continued until the patient arrives at the age of normal menopause, as recommended in all international guidelines.

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References

  1. Izhar R, Husain S, Tahir S, et al. Occult form of premature ovarian insufficiency in women with infertility and oligomenorrhea as assessed by poor ovarian response criteria. J Reprod Infertil. 2017;18(4):361–7.

    PubMed  PubMed Central  Google Scholar 

  2. Guzel Y, Aba YA, Yakin K, Oktem O. Menstrual cycle characteristics of young females with occult primary ovarian insufficiency at initial diagnosis and one-year follow-up with serum AMH level and antral follicle count. PLoS One, 2017. https://doi.org/10.1371/journal.pone.0188334.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Bruni V, Bucciantini S, Ambroggio S. From primary hypergonadotropic amenorrhea to POI: aetiology and therapy. In: Sultan C, Genazzani AR, editors. Frontiers in gynecological endocrinology, ISGE series, Volume 4: Pediatric and adolescent gynecological endocrinology, 2017, pp. 67–110. https://doi.org/10.1007/78933194143317.

  4. Bidet M, Bachelot A, Bissuage E, et al. Resumption of ovarian function and pregnancies in 358 patients with premature ovarian failure. J Clin Endocrinol Metab. 2011;96:3864–72.

    Article  CAS  PubMed  Google Scholar 

  5. Fortuño C, Labarta E. Genetics of primary ovarian insufficiency: a review. J Assist Reprod Genet. 2014;31:1573–85.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Klenov V, Cooper AR. The genetics of POI. In: Santoro NF, Cooper AR, editors. Primary ovarian insufficiency. Switzerland: Springer; 2016. p. 51–73.

    Chapter  Google Scholar 

  7. Hamoda H. The British Menopause Society and Women’s Health Concern recommendations on the management of women with premature ovarian insufficiency. Post Reprod Health. 2017;23(1):22–35.

    Article  PubMed  Google Scholar 

  8. Rossetti R, Ferrari I, Bonomi M, Persani L. Genetics of primary ovarian insufficiency. Clin Genet. 2017;91(2):183–98.

    Article  CAS  PubMed  Google Scholar 

  9. Tucker EJ, Grover SR, Bachelot A, et al. Premature ovarian insufficiency: new perspectives on genetic cause and phenotypic spectrum. Endocr Rev. 2016;37(6):609–35.

    Article  PubMed  Google Scholar 

  10. Jiao X , Ke H, Qin Y, Chen ZJ. Molecular genetics of premature ovarian insufficiency. Trends Endocrinol Metab. 2018. https://doi.org/10.1016/j.tem.2018.07.002. pii: S1043-2760(18)30130-9.

    Article  CAS  Google Scholar 

  11. Katari S, Aarabi M, Kintigh A, et al. Chromosomal instability in women with primary ovarian insufficiency. Hum Reprod. 2018;33(3):531–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bakalov VK, Anasti JN, Calis KA, et al. Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46XX spontaneous premature ovarian failure. Fertil Steril. 2005;84(4):958–65.

    Article  PubMed  Google Scholar 

  13. Doyle N, Banks NK, Wolff EF. Mechanisms of primary ovarian insufficiency. In: Santoro NF, Cooper AR, editors. Primary ovarian insufficiency. Switzerland: Springer; 2016. p. 75–100.

    Chapter  Google Scholar 

  14. Foyouzi N, Green LJ, Camper SA. Etiologies of primary ovarian insufficiency. In: Santoro NF, Cooper AR, editors. Primary ovarian insufficiency. Switzerland: Springer; 2016. p. 19–35.

    Chapter  Google Scholar 

  15. Fowler FA, Bellingham M, Sinclair KD, et al. Impact of endocrine-disrupting compounds (EDCs) on female reproductive health. Mol Cell Endocrinol. 2012;355:231–9.

    Article  CAS  PubMed  Google Scholar 

  16. Hoyer PB, Keating AF. Xenobiotic effects in the ovary: temporary versus permanent infertility. Expert Opin Drug Metab Toxicol. 2014;10:511–23.

    Article  CAS  PubMed  Google Scholar 

  17. Brown S. Endocrine disrupting chemicals associated with earlier menopause. Post Reprod Health. 2015;1:5–6.

    Google Scholar 

  18. Grindler NM, Allsworth JN, Macones GA, et al. Persistent organic pollutants and early menopause in U.S. women. PLoS One. 2015;10(1):e0116057. https://doi.org/10.1371/journal.pone.0116057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sadrzadeh S, Painter RC, van Kasteren YM, et al. Premature ovarian insufficiency and perinatal parameters: a retrospective case-control study. Maturitas. 2017;96:72–6.

    Article  CAS  PubMed  Google Scholar 

  20. Kannel WB. The Framingham study. Br Med J. 1976;2(6046):1255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Rivera CM, Grossardt BR, Rhodes DJ, et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause. 2009;16(1):15–23.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Faubion SS, Kuhle CL, Shuster LT, Rocca WA. Long-term health consequences of premature or early menopause and considerations for management. Climacteric. 2015;18(4):483–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rocca WA, Gazzuola-Rocca L, Smith CY, et al. Accelerated accumulation of multimorbidity after bilateral oophorectomy: a population-based cohort study. Mayo Clin Proc. 2016;91(11):1577–89.

    Article  PubMed  Google Scholar 

  24. Roeters van Lennep JE, Heida KY, Bots ML, Hoek A. Cardiovascular disease risk in women with premature ovarian insufficiency: a systematic review and meta-analysis. Eur J Prev Cardiol. 2016;23(2):178–86.

    Article  PubMed  Google Scholar 

  25. Tao XY, Zuo AZ, Wang JQ, et al. Effect of primary ovarian insufficiency and early natural menopause on mortality: a meta-analysis. Climacteric. 2016;19(1):27–36.

    Article  PubMed  Google Scholar 

  26. Gandhi J, Chen A, Dagur G, et al. Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol. 2016;215(6):704–11.

    Article  PubMed  Google Scholar 

  27. Gibson-Helm MI, Teede H, Vincent A. Symptoms, health behavior and understanding of menopause therapy in women with premature menopause. Climacteric. 2014;17(6):666–73.

    Article  CAS  PubMed  Google Scholar 

  28. Van der Stege JG, Groen H, van Zadelhoff SJ, et al. Decreased androgen concentrations and diminished general and sexual well-being in women with premature ovarian failure. Menopause. 2008;15:23–31.

    Article  PubMed  Google Scholar 

  29. de Almeida DM, Benetti-Pinto CL, Makuch MY. Sexual function of women with premature ovarian failure. Menopause. 2011;18:262–6.

    Article  PubMed  Google Scholar 

  30. Allshouse AA, Semple AL. Signs and symptoms of primary ovarian insufficiency. In: Santoro NF, Cooper AR, editors. Primary ovarian insufficiency. Switzerland: Springer; 2016. p. 37–49.

    Chapter  Google Scholar 

  31. Lett C, Valadares ALR, Baccaro LF, Pedro AO, Filho JL, Lima M, Costa-Paiva L. Is the age at menopause a cause of sexual dysfunction? A Brazilian population-based study. Menopause. 2018;25(1):70–6.

    Article  PubMed  Google Scholar 

  32. Graziottin A, Koachaki PE, Rodenberg CA, Donnerstein L. The prevalence of sexual active desire disorder in surgically menopausal women: an epidemiological study of women in four European countries. J Sex Med. 2009;6(8):2143–53.

    Article  PubMed  Google Scholar 

  33. Madalinska JB, van Beurden M, Bleiker EM, et al. The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy. J Clin Oncol. 2006;24:3576–82.

    Article  PubMed  Google Scholar 

  34. Løkkegaard E, Jovanovic Z, Heitmann BL, et al. The association between early menopause and risk of ischaemic heart disease: influence of hormone therapy. Maturitas. 2006;53(2):226–33.

    Article  CAS  PubMed  Google Scholar 

  35. Wellons M, Ouyang P, Schreiner PJ, Herrington DM, Vaidya D. Early menopause predicts future coronary heart disease and stroke: the multi-ethnic study of atherosclerosis. Menopause. 2012;19(10):1081–7.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Rahman I, Åkesson A, Wolk A. Relationship between age at natural menopause and risk of heart failure. Menopause. 2015;22(1):12–6.

    Article  PubMed  Google Scholar 

  37. Kalantaridou SN, Naka KK, Bechlioulis A, et al. Premature ovarian failure, endothelial dysfunction and estrogen-progestogen replacement. Trends Endocrinol Metab. 2006;17(3):101–9.

    Article  CAS  PubMed  Google Scholar 

  38. Yorgun H, Tokgözoğlu L, Canpolat U, et al. The cardiovascular effects of premature ovarian failure. Int J Cardiol. 2013;168(1):506–10.

    Article  PubMed  Google Scholar 

  39. Moreau KL, Hildreth KL, Meditz AL, et al. Endothelial function is impaired across the stages of the menopause transition in healthy women. J Clin Endocrinol Metab. 2012;97(12):4692–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ates S, Yesil G, Sevket O, et al. Comparison of metabolic profile and abdominal fat distribution between karyotypically normal women with premature ovarian insufficiency and age matched controls. Maturitas. 2014;79(3):306–10.

    Article  PubMed  Google Scholar 

  41. Daan N, Muka T, Koster M, et al. Cardiovascular risk in women with premature ovarian insufficiency compared to premenopausal women at middle age. J Clin Endocrinol Metab. 2016;101:3306–15.

    Article  CAS  PubMed  Google Scholar 

  42. Knauff EA, Westerveld HE, Goverde AJ, et al. Lipid profile of women with premature ovarian failure. Menopause. 2008;15(5):919–23.

    Article  PubMed  Google Scholar 

  43. Senöz S, Direm B, Gülekli B, Gökmen O. Estrogen deprivation, rather than age, is responsible for the poor lipid profile and carbohydrate metabolism in women. Maturitas. 1996;25(2):107–14.

    Article  PubMed  Google Scholar 

  44. Gulhan I, Bozkaya G, Uyar I, Oztekin D, Pamuk BO, Dogan E. Serum lipid levels in women with premature ovarian failure. Menopause. 2012;19(11):1231–4.

    Article  PubMed  Google Scholar 

  45. Sari N, Engin-Üstün Y, Kiyak Çağlayan E, et al. Evaluation of cardiovascular disease risk in women with surgically induced menopause. Gynecol Endocrinol. 2016;32(6):498–501.

    Article  PubMed  Google Scholar 

  46. Muka T, Asllanaj E, Avazverdi N, et al. Age at natural menopause and risk of type 2 diabetes: a prospective cohort study. Diabetologia. 2017;60(10):1951–60.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Rocca W, Gazzuola Rocca L, Smith C, et al. Cohort profile: the Mayo Clinic cohort study of oophorectomy and aging-2 (MOA-2) in Olmsted County, Minnesota (USA). BMJ Open. 2017;7(11):e018861.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Rosendahl M, Simonsen MK, Kjer JJ, et al. The influence of unilateral oophorectomy on the age of menopause. Climacteric. 2017;20(6):540–4.

    Article  CAS  PubMed  Google Scholar 

  49. Pirimoglu ZM, Arslan C, Buyukbayrak EE, et al. Glucose tolerance of premenopausal women after menopause due to surgical removal of ovaries. Climacteric. 2011;14(4):453–7.

    Article  CAS  PubMed  Google Scholar 

  50. Appiah D, Schreiner PJ, Nwabuo CC, et al. The association of surgical versus natural menopause with future left ventricular structure and function: the coronary artery risk development in young adults (CARDIA) study. Menopause. 2017;24(11):1269–76.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Anasti JN, Kalantaridou SN, Kimzey LM, et al. Bone loss in young women with karyotypically normal spontaneous premature ovarian failure. Obstet Gynecol. 1998;91(1):12–5.

    Article  CAS  PubMed  Google Scholar 

  52. Uygur D, Sengül O, Bayar D, et al. Bone loss in young women with premature ovarian failure. Arch Gynecol Obstet. 2005;273(1):17–9.

    Article  PubMed  Google Scholar 

  53. Popat VB, Calis KA, Vanderhoof VH, et al. Bone mineral density in estrogen-deficient young women. J Clin Endocrinol Metab. 2009;94(7):2277–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Amarante F, Vilodre LC, Maturana MA, Spritzer PM. Women with primary ovarian insufficiency have lower bone mineral density. Braz J Med Biol Res. 2011;44(1):78–83.

    Article  CAS  PubMed  Google Scholar 

  55. Francucci CM, Romagni P, Camilletti A, et al. Effect of natural early menopause on bone mineral density. Maturitas. 2008;59(4):323–8.

    Article  CAS  PubMed  Google Scholar 

  56. van Der Voort DJ, van Der Weijer PH, Barentsen R. Early menopause: increased fracture risk at older age. Osteoporos Int. 2003;14(6):525–30.. Epub 2003 Apr 30

    Article  Google Scholar 

  57. Yoshida T, Takahashi K, Yamatani H, et al. Impact of surgical menopause on lipid and bone metabolism. Climacteric. 2011;14(4):445–52.

    Article  CAS  PubMed  Google Scholar 

  58. Bahar S, Abali R, Guzel S, et al. Comparison of the acute alterations in serum bone turnover markers and bone mineral density among women with surgical menopause. Eur J Obstet Gynecol Reprod Biol. 2011;159(1):194–7.

    Article  PubMed  Google Scholar 

  59. Faienza MF, Brunetti G, Ventura A, et al. Mechanisms of enhanced osteoclastogenesis in girls and young women with Turner’s syndrome. Bone. 2015;81:228–36.

    Article  CAS  PubMed  Google Scholar 

  60. Ross JL, Long LM, Feuillan P, et al. Normal bone density of the wrist and spine and increased wrist fractures in girls with Turner’s syndrome. J Clin Endocrinol Metab. 1991;73:355–9.

    Article  CAS  PubMed  Google Scholar 

  61. Gravholt CH, Vestergaard P, Hermann AP, et al. Increased fracture rates in Turner’s syndrome: a nation-wide questionnaire survey. Clin Endocrinol. 2003;59:89–96.

    Article  Google Scholar 

  62. Peralta López M, Miras M, Silvano L, et al. Vitamin D receptor genotypes are associated with bone mass in patients with Turner syndrome. J Pediatr Endocrinol Metab. 2011;24(5–6):307–12.

    PubMed  Google Scholar 

  63. Roman-Blas JA, Castañeda S, Largo R, Herrero-Beaumont G. Osteoarthritis associated with estrogen deficiency. Arthritis Res Ther. 2009;11(5):241.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Quinelato V, Bonato LL, Vieira AR, et al. Association between polymorphisms in the genes of estrogen receptors and the presence of temporomandibular disorders and chronic arthralgia. J Oral Maxillofac Surg. 2018;76(2):314.e1–9.

    Article  Google Scholar 

  65. Blümel JE, Chedraui P, Baron G, et al. Menopause could be involved in the pathogenesis of muscle and joint aches in mid-aged women. Maturitas. 2013;75(1):94–100.

    Article  PubMed  Google Scholar 

  66. Xiao Y-P, Tian F-M, Dai M-W, et al. Are estrogen-related drugs new alternatives for the management of osteoarthritis? Arthritis Res Ther. 2016;18:151.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Talsania M, Scofield RH. Menopause and rheumatic disease. Rheum Dis Clin North Am. 2017;43(2):287–302.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Fenton A, Panay N. Estrogen, menopause and joints. Climacteric. 2016;19(2):107–8.

    Article  PubMed  Google Scholar 

  69. Packham JC, Hall MA. Premature ovarian failure in women with juvenile idiopathic arthritis (JIA). Clin Exp Rheumatol. 2003;21(3):347–50.

    CAS  PubMed  Google Scholar 

  70. Wong LE, Huang WT, Pope JE, et al. Effect of age at menopause on disease presentation in early rheumatoid arthritis: results from the Canadian Early Arthritis Cohort. Arthritis Care Res (Hoboken). 2015;67(5):616–23.

    Article  Google Scholar 

  71. Pikwer M, Nilsson J-Å, Bergström U, et al. Early menopause and severity of rheumatoid arthritis in women older than 45 years. Arthritis Res Ther. 2012;14:R190.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Podfigurna-Stopa A, Czyzyk A, Grymowicz M et al. Premature ovarian insufficiency: the context of long-term effects. J Endocrinol Investig 2016. https://doi.org/10.1007/s40618-016-0467.

  73. Nappi RE, Sinforiani E, Mauri M, et al. Memory functioning at menopause: impact of age in ovariectomized women. Gynecol Obstet Investig. 1999;47:29–36.

    Article  CAS  Google Scholar 

  74. Farrag AK, Khedr EM, Abdel-Aleem H, Rageh TA. Effect of surgical menopause on cognitive functions. Dement Geriatr Cogn Disord. 2002;13:193–8.

    Article  CAS  PubMed  Google Scholar 

  75. Rocca WA, Shuster LT, Grossardt BR, et al. Long-term effects of bilateral oophorectomy on brain aging: unanswered questions from the Mayo Clinic Cohort Study of Oophorectomy and Aging. Womens Health. 2009;5(1):39–48.

    Google Scholar 

  76. Phung TK, Waltoft BL, Laursen TM, et al. Hysterectomy, oophorectomy and risk of dementia: a nationwide historical cohort study. Dement Geriatr Cogn Disord. 2010;30(1):43–50.

    Article  PubMed  Google Scholar 

  77. Bove R, Secor E, Chibnik LB, Barnes LL, et al. Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women. Neurology. 2014;82(3):222–9.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Soni M, Hogervost E. Premature ovarian insufficiency and neurological function. Minerva Endocrinol. 2014;39(3):189–99.

    CAS  PubMed  Google Scholar 

  79. Kangas M, Henry JL, Bryant RA. Post-traumatic stress disorder following cancer. A conceptual and empirical review. Clin Psychol Rev. 2002;22(4):499–524.

    Article  PubMed  Google Scholar 

  80. Halbreich U, Rojansky N, Palter S, et al. Estrogen augments serotonergic activity in postmenopausal women. Biol Psychiatry. 1995;37(7):434–41.

    Article  CAS  PubMed  Google Scholar 

  81. Morton TL, Gattermeir DJ, Petersen CA, et al. Steady-state pharmacokinetics following application of a novel transdermal estradiol spray in healthy postmenopausal women. J Clin Pharmacol. 2009;49(9):1037–46.

    Article  CAS  PubMed  Google Scholar 

  82. Kovács G, Zelei T, Vokó Z. Comparison of efficacy and local tolerability of estradiol metered-dose transdermal spray to estradiol patch in a network meta-analysis. Climacteric. 2016;19(5):488–95.

    Article  PubMed  CAS  Google Scholar 

  83. Bhavnani BR, Stanczyk FZ. Pharmacology of conjugated equine estrogens: efficacy, safety and mechanism of action. J Steroid Biochem Mol Biol. 2014;142:16–29.

    Article  CAS  PubMed  Google Scholar 

  84. Apter D, Zimmerman Y, Beekman L, et al. Bleeding pattern and cycle control with estetrol-containing combined oral contraceptives: results from a phase II, randomised, dose-finding study (FIESTA). Contraception. 2016;94(4):366–73.

    Article  CAS  PubMed  Google Scholar 

  85. Kluft C, Zimmerman Y, Mawet M, et al. Reduced hemostatic effects with drospirenone-based oral contraceptives containing estetrol vs. ethinyl estradiol. Contraception. 2017;95(2):140–7.

    Article  CAS  PubMed  Google Scholar 

  86. Valéra MC, Noirrit-Esclassan E, Dupuis M et al. Effect of estetrol, a selective nuclear estrogen receptor modulator, in mouse models of arterial and venous thrombosis. Mol Cel Endocrinol. 2018. https://doi.org/10.1016/j.mce.2018.06.010.

    Article  PubMed  CAS  Google Scholar 

  87. Sitruk-Ware R. 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 

  88. Scarabin PY. Hormone therapy and venous thromboembolism among postmenopausal women. Front Horm Res. 2014;43:21–32.

    Article  PubMed  Google Scholar 

  89. Cicinelli E, de Ziegler D, Bulletti C, et al. Direct transport of progesterone from vagina to uterus. Obstet Gynecol. 2000;95(3):403–6.

    CAS  PubMed  Google Scholar 

  90. Archer DF, Fahy GE, Viniegra-Sibal A, et al. Initial and steady-state pharmacokinetics of a vaginally administered formulation of progesterone. Am J Obstet Gynecol. 1995;173(2):471–7.

    Article  CAS  PubMed  Google Scholar 

  91. Levy T, Gurevitch S, Bar-Hava I, et al. Pharmacokinetics of natural progesterone administered in the form of a vaginal tablet. Hum Reprod. 1999;14(3):606–10.

    Article  CAS  PubMed  Google Scholar 

  92. Maxson WS, Hargrove JT. Bioavailability of oral micronized progesterone. Fertil Steril. 1985;44:622–6.

    Article  CAS  PubMed  Google Scholar 

  93. Nahoul K, Dehennin L, Scholler R. Radioimmunoassay of plasma progesterone after oral administration of micronized progesterone. J Steroid Biochem. 1987;26:241–9.

    Article  CAS  PubMed  Google Scholar 

  94. Hargrove JT, Maxson WS, Wentz AC. Absorption of oral progesterone is influenced by vehicle and particle size. Am J Obstet Gynecol. 1989;161:948–51.

    Article  CAS  PubMed  Google Scholar 

  95. Stute P, Neulen J, Wild L. The impact of micronized progesterone on the endometrium: a systematic review. Climacteric. 2016;19(4):316–28.

    Article  CAS  PubMed  Google Scholar 

  96. Rosano GM, Vitale C, Silvestri A, Fini M. Metabolic and vascular effect of progestins in post-menopausal women. Implications for cardioprotection. Maturitas. 2003;10(46 Suppl 1):S17–29.

    Article  CAS  Google Scholar 

  97. Mittal M, Savvas M, Arya R. A randomised controlled trial comparing the effects of micronized progesterone to medroxyprogesterone acetate on cardiovascular health, lipid metabolism and the coagulation cascade in women with premature ovarian insufficiency: study protocol and review of the literature. Menopause. 2013;19(3):127–32.

    Article  Google Scholar 

  98. Campagnoli C, Ambroggio S, Lotano MR, Peris C. Progestogen use in women approaching the menopause and breast cancer risk. Maturitas. 2009;62(4):338–42.

    Article  CAS  PubMed  Google Scholar 

  99. Asi N, Mohammed K, Haydour Q, et al. Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis. Syst Rev. 2016;5:121.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Gompel A, Plu-Bureau G. Progesterone, progestins and the breast in menopause treatment. Climacteric. 2018. https://doi.org/10.1080/13697137.2018.1476483.

    Article  CAS  PubMed  Google Scholar 

  101. Stute P, Wildt L, Neulen J. The impact of micronized progesterone on breast cancer risk: a systematic review. Climacteric. 2018;21(2):111–22.

    Article  CAS  PubMed  Google Scholar 

  102. Rižner TL, Brožič P, Doucette C, et al. Selectivity and potency of the retroprogesterone dydrogesterone in vitro. Steroids. 2011;76(6):607–15.

    Article  PubMed  CAS  Google Scholar 

  103. Scholer HF, Reerink EH, Westerhof P. The progestational effect of a new series steroids. Acta Physiol Pharmacol Neerl. 1960;9:134–6.

    CAS  PubMed  Google Scholar 

  104. Carp HJ. Progestogens in the threatened miscarriage. In: Carp HJ, editor. Progestogens in obstetrics and gynecology. Switzerland: Springer; 2015. p. 65–78.

    Chapter  Google Scholar 

  105. Barbosa MW, Silva LR, Navarro PA, et al. Dydrogesterone versus progesterone for luteal-phase support: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2015;48(2):161–70.

    Article  Google Scholar 

  106. Stevenson JC, Panay N, Pexman-Fieth C. Oral estradiol and dydrogesterone combination therapy in postmenopausal women: review of efficacy and safety. Maturitas. 2013;76(1):10–21.

    Article  CAS  PubMed  Google Scholar 

  107. Tomic V, Tomic J, Klaic DZ, et al. Oral dydrogesterone versus vaginal progesterone gel in the luteal phase support: randomized controlled trial. Eur J Obstet Gynecol Reprod Biol. 2015;186:49–53.

    Article  CAS  PubMed  Google Scholar 

  108. deValkdeRoo GW, Netelenbos JC, Peters-Muller IR, et al. Continuously combined hormone replacement therapy and bone turnover: the influence of dydrogesterone dose, smoking and initial degree of bone turnover. Maturitas. 1997;28:153–62.

    Article  CAS  PubMed  Google Scholar 

  109. Schindler AE, Campagnoli C, Druckmann R, et al. Classification and pharmacology of progestins. Maturitas. 2003;46(Suppl 1):S7–S16.

    Article  CAS  PubMed  Google Scholar 

  110. Stanczyk FZ, Hapgood JP, Winer S, Mishell DR Jr. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr Rev. 2013;34(2):171–208.

    Article  CAS  PubMed  Google Scholar 

  111. Panay N, Kalu E. Management of premature ovarian failure. Best Pract Res Clin Obstet Gynaecol. 2009;23(1):129–40.

    Article  PubMed  Google Scholar 

  112. Tønnes Pedersen A, Cleemann L, Main KM, Juul A. Transition in pediatric and adolescent hypogonadal girls: gynecological aspects, estrogen replacement therapy, and contraception. Endocr Dev. 2018;33:113–27.

    Article  PubMed  Google Scholar 

  113. van Kasteren YM, Schoemaker J. Premature ovarian failure: a systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy. Hum Reprod Update. 1999;5(5):483–92.

    Article  PubMed  Google Scholar 

  114. Bidet M, Bachelot A, Touraine P. Premature ovarian failure: predictability of intermittent ovarian function and response to ovulation induction agents. Curr Opin Obstet Gynecol. 2008;20(4):416–20.

    Article  PubMed  Google Scholar 

  115. Iversen L, Sivasubramaniam S, Lee AJ, et al. Lifetime cancer risk and combined oral contra-ceptives: the Royal College of General Practitioners’ Oral Contraception Study. Am J Obstet Gynecol. 2017;216(6):580.e1–9.

    Article  CAS  Google Scholar 

  116. Lidegaard Ø, Nielsen LH, Skovlund CW, et al. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001–2009. BMJ. 2011;343:d6423.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Manzoli L, De Vito C, Marzuillo C, et al. Oral contraceptives and venous thromboembolism: a systematic review and meta-analysis. Drug Saf. 2012;35(3):191–205.

    CAS  PubMed  Google Scholar 

  118. de Bastos M, Stegeman BH, Rosendaal FR, et al. Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev. 2014;3:CD010813.

    Google Scholar 

  119. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2015;350:h2135.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Dragoman MV, Tepper NK, Fu R, et al. A systematic review and meta-analysis of venous thrombosis risk among users of combined oral contraception. Int J Gynaecol Obstet. 2018;141(3):287–94.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Dinger J, Do Minh T, Heinemann K. Impact of estrogen type on cardiovascular safety of combined oral contraceptives. Contraception. 2016;94(4):328–39.

    Article  CAS  PubMed  Google Scholar 

  122. Raps M, Helmerhorst F, Fleischer K, et al. Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal contraceptives. J Thromb Haemost. 2012;10(6):992–7.

    Article  CAS  PubMed  Google Scholar 

  123. Fleischer K, van Vliet HA, Rosendaal FR, et al. Effects of the contraceptive patch, the vaginal ring and an oral contraceptive on APC resistance and SHBG: a cross-over study. Thromb Res. 2009;123(3):429–35.

    Article  CAS  PubMed  Google Scholar 

  124. Plu-Bureau G, Hugon-Rodin J, Maitrot-Mantelet L, Canonico M. Hormonal contraceptives and arterial disease: an epidemiological update. Best Pract Res Clin Endocrinol Metab. 2013;27(1):35–45.

    Article  CAS  PubMed  Google Scholar 

  125. Weill A, Dalichampt M, Raguideau F, et al. Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study. BMJ. 2016;353:i2002.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Roach RE, Helmerhorst FM, Lijfering WM, et al. Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke. Cochrane Database Syst Rev. 2015;8:CD011054.

    Google Scholar 

  127. Lidegaard Ø, Løkkegaard E, Jensen A, et al. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med. 2012;366(24):2257–66.

    Article  CAS  PubMed  Google Scholar 

  128. Dinger J, Möhner S, Heinemann K. Cardiovascular risks associated with the use of dro-spirenone-containing combined oral contraceptives. Contraception. 2016;93(5):378–85.

    Article  CAS  PubMed  Google Scholar 

  129. Luukkainen T. The levonorgestrel intrauterine system: therapeutic aspects. Steroids. 2000;65(10–11):699–702.

    Article  CAS  PubMed  Google Scholar 

  130. Apter D, Gemzell-Danielsson K, Hauck B, et al. Pharmacokinetics of two low-dose levonorgestrel-releasing intrauterine systems and effects on ovulation rate and cervical function: pooled analyses of phase II and III studies. Fertil Steril. 2014;101(6):1656–62.

    Article  CAS  PubMed  Google Scholar 

  131. Benecerraf BR, Shipp TD, Lyons JG, Brombley B. Width of the normal uterine cavity in premenopausal women and effect of parity. Obstet Gynecol. 2010;116(2 Pt 1):305–10.

    Article  Google Scholar 

  132. Gemzell-Danielsson K, Apter D, Lukkari-Laxc E, et al. Overcoming barriers to levonorgestrel-releasing intrauterine system placement: an evaluation of placement of LNG-IUS 8 using the modified EvoInserter® in a majority nulliparous population. Contraception. 2017;96:426–31.

    Article  PubMed  Google Scholar 

  133. Weisberg E, Ayton R, Darling G, et al. Endometrial and vaginal effect of low dose estradiol delivered by vaginal ring or vaginal tablet. Climacteric. 2005;8(1):83–92.

    Article  CAS  PubMed  Google Scholar 

  134. Bachmann G. Estradiol-releasing vaginal ring delivery system for urogenital atrophy. Experience over the past decade. J Reprod Med. 1998;43(11):991–8.

    CAS  PubMed  Google Scholar 

  135. Simon J, Nachtigall L, Gut R, et al. Effective treatment of vaginal atrophy with an ultra-low-dose estradiol vaginal tablet. Obstet Gynecol. 2008;112(5):1053–60.

    Article  CAS  PubMed  Google Scholar 

  136. Delgado JL, Estevez J, Radicioni M, et al. Pharmacokinetics and preliminary efficacy of two vaginal gel formulations of ultra-low-dose estriol in postmenopausal women. Climacteric. 2016;19(2):172–80.

    Article  CAS  PubMed  Google Scholar 

  137. Santos I, Clissold S. Urogenital disorders associated with oestrogen deficiency: the role of promestriene as topical oestrogen therapy. Gynecol Endocrinol. 2010;26:644–51.

    Article  CAS  PubMed  Google Scholar 

  138. Del Pup L, Postruznik D, Corona G. Effect of one-month treatment with vaginal promestriene on serum estrone sulfate levels in cancer patients: a pilot study. Maturitas. 2012;72(1):93–4.

    Article  PubMed  CAS  Google Scholar 

  139. Del Pup L, Di Francia R, Cavaliere C, et al. Promestriene, a specific topic estrogen. Review of 40 years of vaginal atrophy treatment: is it safe even in cancer patients? Anticancer Drugs. 2013;24:989–98.

    Article  PubMed  CAS  Google Scholar 

  140. Davis SR, McCloud P, Strauss BJ, Burger H. Testosterone enhances estradiol’s effects on postmenopausal bone density and sexuality. Maturitas. 2008;61(1–2):17–26.

    Article  PubMed  Google Scholar 

  141. Kingsberg S, Shifren J, Wekselman K, et al. Evaluation of the clinical relevance of benefits associated with transdermal testosterone treatment in postmenopausal women with hypoactive sexual desire disorder. J Sex Med. 2007;4(4 Pt 1):1001–8.

    Article  CAS  PubMed  Google Scholar 

  142. Zuckerman-Levin N, Frolova-Bishara T, Militianu D, et al. Androgen replacement therapy in Turner syndrome: a pilot study. J Clin Endocrinol Metab. 2009;94:4820–7.

    Article  CAS  PubMed  Google Scholar 

  143. Popat VB, Calis KA, Kalantaridou SN, et al. 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(9):3418–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Guerrieri GM, Martinez PE, Klug SP, et al. Effects of physiologic testosterone therapy on quality of life, self-esteem, and mood in women with primary ovarian insufficiency. Menopause. 2014;21(9):952–61.

    Article  PubMed  PubMed Central  Google Scholar 

  145. Soman M, Huang LC, Cai WH et al. Serum androgen profiles in women with premature ovarian insufficiency: a systematic review and meta-analysis. Menopause 2018. https://doi.org/10.1097/GME.0000000000001161.

    Article  PubMed  Google Scholar 

  146. Nagels HE, Rishworth JR, Siristatidis CS, Kroon B. Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction. Cochrane Database Syst Rev. 2015;11:CD009749.

    Google Scholar 

  147. Wong QHY, Yeung TWY, Yung SSF, et al. The effect of 12-month dehydroepiandrosterone supplementation on the menstrual pattern, ovarian reserve markers, and safety profile in women with premature ovarian insufficiency. J Assist Reprod Genet. 2018;35(5):857–62.

    Article  PubMed  PubMed Central  Google Scholar 

  148. Sullivan SD. Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertil Steril. 2016;106(7):1588–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Christ JP, Gunning MN, Palla G, Eijkemans MJC, et al. Estrogen deprivation and cardiovascular disease risk in primary ovarian insufficiency. Fertil Steril. 2018;109(4):594–600.

    Article  CAS  PubMed  Google Scholar 

  150. Strandberg TE, Ylikorkala O, Tikkanen MJ. Differing effects of oral and transdermal hormone replacement therapy on cardiovascular risk factors in healthy postmenopausal women. Am J Cardiol. 2003;92:212–4.

    Article  CAS  PubMed  Google Scholar 

  151. Cuadros JI, Fernandez-Alonso MA, Chedraui P, et al. Metabolic and hormonal parameters in post-menopausal women 10 years after transdermal oestradiol treatment, alone or combined to micronised oral pro-gesterone. Gynecol Endocrinol. 2011;27(3):156–62.

    Article  CAS  PubMed  Google Scholar 

  152. Ockner RK, Lysenko N, Manning JA, et al. Sex steroid modulation of fatty acid utilization and fatty acid binding protein concentration in rat liver. J Clin Invest. 1980;65:1013–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Leung H, Wang JJ, Rochtchina E, et al. Does hormone replacement therapy influence retinal microvascular caliber? Microvasc Res. 2004;67:48–54.

    Article  CAS  PubMed  Google Scholar 

  154. 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 

  155. Vrablik M, Fait T, Kovar J, et al. Oral but not transdermal estrogen replacement therapy changes the composition of plasma lipoproteins. Metabolism. 2008;57:1088–92.

    Article  CAS  PubMed  Google Scholar 

  156. Cortés-Prieto J, Vicente-Hernanz ML, Cortés-García A, et al. Hormone replacement therapy: evolution of body mass index, bone mineral density, and lipid profile. Horm Mol Biol Clin Invest. 2013;13(2):19–40.

    Google Scholar 

  157. Giordano R, Fabio D, Lanfranco F, et al. Metabolic and cardiovascular outcomes in a group of adult patients with Turner’s syndrome under hormonal replacement therapy. Eur J Endocrinol. 2011;164:819–26.

    Article  CAS  PubMed  Google Scholar 

  158. Irzyniec TJ, Jeż W. The influence of hormonal replacement and growth hormone treatment on the lipids in Turner syndrome. Gynecol Endocrinol. 2014;30(3):250–3.

    Article  CAS  PubMed  Google Scholar 

  159. Gawlik A, Hankus M, Such K, et al. Hypogonadism and sex steroid replacement therapy in girls with Turner syndrome. J Pediatr Adolesc Gynecol. 2016;29(6):542–50.

    Article  PubMed  Google Scholar 

  160. Stuenkel CA. Menopause, hormone therapy and diabetes. Climacteric. 2017;20(1):11–21.

    Article  CAS  PubMed  Google Scholar 

  161. Stojanovic ND, Kwong P, Byrne DJ, et al. The effects of transdermal estradiol alone or with cyclical dydrogesterone on markers of cardiovascular disease risk in postmenopausal women with type 2 diabetes: a pilot study. Angiology. 2003;54:391–9.

    Article  CAS  PubMed  Google Scholar 

  162. Trémollières FA, Pouilles JM, Cauneille C, Ribot C. Coronary heart disease risk factors and menopause: a study in 1684 French women. Atherosclerosis. 1999;142(2):415–23.

    Article  PubMed  Google Scholar 

  163. Langrish JP, Mills NL, Bath LE, et al. Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure. Hypertension. 2009;53(5):805–11.

    Article  CAS  PubMed  Google Scholar 

  164. Scarabin PY, Alhenc-Gelas M, Plu-Bureau G, et al. Effects of oral and transdermal estro-gen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. Arterioscler Thromb Vasc Biol. 1997;17(11):371–8.

    Article  Google Scholar 

  165. Lowe GD, Upton MN, Rumley A, et al. Different effects of oral and transdermal hormone replacement therapies on factor IX, APC resistance, t-PA, PAI and C-reactive protein--a cross-sectional population survey. Thromb Haemost. 2001;86(2):550–6.

    CAS  PubMed  Google Scholar 

  166. Madsen JS, Kristensen SR, Gram J, et al. Positive impact of hormone replacement therapy on the fibrinolytic system: a long-term randomized controlled study in healthy postmenopausal women. J Thromb Haemost. 2003;1:1984–91.

    Article  CAS  PubMed  Google Scholar 

  167. Post MS, van der Mooren MJ, van Baal WM, et al. Effects of low-dose oral and transdermal estrogen replacement therapy on hemostatic factors in healthy postmenopausal women: a randomized placebo-controlled study. Am J Obstet Gynecol. 2003;189:1221–7.

    Article  CAS  PubMed  Google Scholar 

  168. Fait T, Vrablik M, Zizka Z, et al. Changes in hemostatic variables induced by estrogen replacement therapy: comparison of transdermal and oral administration in a crossover-designed study. Gynecol Obstet Investig. 2008;65(1):47–51.

    Article  CAS  Google Scholar 

  169. Roach RE, Lijfering WM, van Hylckama Vlieg A. The risk of venous thrombosis in individuals with a history of superficial vein thrombosis and acquired venous thrombotic risk factors. Blood. 2013;122:4264–9.

    Article  CAS  PubMed  Google Scholar 

  170. Canonico M. Hormone therapy and risk of venous thromboembolism among postmenopausal women. Maturitas. 2015;82(3):304–7.

    Article  CAS  PubMed  Google Scholar 

  171. Bondy CA. r the Turner Syndrome Consensus Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007;92:10–25.

    Article  CAS  PubMed  Google Scholar 

  172. Davenport ML. Moving toward an understanding of hormone replacement therapy in adolescent girls looking through the lens of Turner syndrome. Ann N Y Acad Sci. 2008;1135:126–37.

    Article  CAS  PubMed  Google Scholar 

  173. Ankarberg-Lindgren C, Kriström B, Norjavaara E. Physiological estrogen replacement therapy for puberty induction in girls: a clinical observational study. Horm Res Paediatr. 2014;81(4):239–44.

    Article  CAS  PubMed  Google Scholar 

  174. Cleemann L, Hjerrild BE, Lauridsen A, et al. Long-term hormone replacement therapy preserves bone mineral density in Turner syndrome. Eur J Endocrinol. 2009;161:251–7.

    Article  CAS  PubMed  Google Scholar 

  175. Nabhan ZM, Dimeglio LA, Qi R, et al. Conjugated oral versus transdermal estrogen replacement in girls with Turner syndrome: a pilot comparative study. J Clin Endocrinol Metab. 2009;94(6):2009–14.

    Article  CAS  PubMed  Google Scholar 

  176. Lanes R, Gunczler P, Esaa S, et al. Decreased bone mass despite long-term estrogen replacement therapy in young women with Turner’s syndrome and previously normal bone density. Fertil Steril. 1999;72(5):896–9.

    Article  CAS  PubMed  Google Scholar 

  177. Benetti-Pinto CL, Bedone A, Magna LA, Marques-Neto JF. Factors associated with the reduction of bone density in patients with gonadal dysgenesis. Fertil Steril. 2002;77(3):571–5.

    Article  PubMed  Google Scholar 

  178. Chan CC, Tang OS, Lau WN, Tang GW. Bone turnover in young hypoestrogenic women on hormonal therapy. Eur J Obstet Gynecol Reprod Biol. 2006;124(2):204–6.

    Article  CAS  PubMed  Google Scholar 

  179. Kodama M, Komura H, Kodama T, et al. Estrogen therapy initiated at an early age increases bone mineral density in Turner syndrome patients. Endocr J. 2012;59(2):153–9.

    Article  CAS  PubMed  Google Scholar 

  180. Nakamura T, Tsuburai T, Tokinaga A, et al. Efficacy of estrogen replacement therapy (ERT) on uterine growth and acquisition of bone mass in patients with Turner syndrome. Endocr J. 2015;62(11):965–70.

    Article  CAS  PubMed  Google Scholar 

  181. Crofton PM, Evans N, Bath LE, et al. Physiological versus standard sex steroid replacement in young women with premature ovarian failure: effects on bone mass acquisition and turnover. Clin Endocrinol. 2010;73:707–14.

    Article  CAS  Google Scholar 

  182. Cartwright B, Robinson J, Seed PT, et al. 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(9):3497–505.

    Article  CAS  PubMed  Google Scholar 

  183. Giraldo H, Benetti-Pinto C, Ferreira V, et al. Standard hormone therapy is inadequate for bone density in premature ovarian insufficiency. Gynecol Endocrinol. 2017;33(4):283–6.

    Article  CAS  PubMed  Google Scholar 

  184. Lindsay R. The menopause: sex steroids and osteoporosis. Clin Obstet Gynecol. 1987;30:847–59.

    Article  CAS  PubMed  Google Scholar 

  185. Bachelot A, Nicolas C, Gricourt S, et al. Poor compliance to hormone therapy and decreased bone mineral density in women with premature ovarian insufficiency. PLoS One. 2016;11(12):e0164638.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  186. ACOG Committee Opinion, Number 698. Hormone therapy in primary ovarian insufficiency. 2017;129(5).

    Google Scholar 

  187. Webber L, Davies M, Anderson R, et al. Management of women with premature ovarian insufficiency. Hum Reprod. 2016;31(5):926–37.

    Article  CAS  PubMed  Google Scholar 

  188. Gambacciani M, Biglia N, Cagnacci A, et al. Menopause and hormone replacement therapy: the 2017 recommendations of the Italian Menopause Society. Minerva Ginecol. 2018;70(1):27–34.

    PubMed  Google Scholar 

  189. Shifren JL, Braunstein GD, Simon JA, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med. 2000;343:682–8.

    Article  CAS  PubMed  Google Scholar 

  190. Floter A, Nathorst-Boos J, Carlstrom K, von Schoultz B. Addition of testosterone to estrogen replacement therapy in oophorectomized women: effects on sexuality and well-being. Climacteric. 2002;5:357–65.

    Article  CAS  PubMed  Google Scholar 

  191. Braunstein GD, Sundwall DA, Katz M, et al. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Arch Intern Med. 2005;165:1582–9.

    Article  CAS  PubMed  Google Scholar 

  192. Davis SR, van der Mooren MJ, van Lunsen RH, et al. Efficacy and safety of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Menopause. 2006;13:387–96.

    Article  PubMed  Google Scholar 

  193. Nachtigall L, Casson P, Lucas J, et al. Safety and tolerability of testosterone patch therapy for up to 4 years in surgically menopausal women receiving oral or transdermal oestrogen. Gynecol Endocrinol. 2011;27:39–48.

    Article  CAS  PubMed  Google Scholar 

  194. Richardson A, West E, Cust M. Hormone replacement therapy in pre-menopausal women undergoing bilateral salpingo-oophorectomy for benign disease: a review of practice. Post Reprod Health. 2017;23(2):63–70.

    Article  PubMed  Google Scholar 

  195. Edey KA, Rundle S, Hickey M. Hormone replacement therapy for women previously treated for endometrial cancer. Cochrane Database Syst Rev. 2018;5:CD008830.

    PubMed  Google Scholar 

  196. Kuhle CL, Kapoor E, Sood R, et al. Menopausal hormone therapy in cancer survivors: a narrative review of the literature. Maturitas. 2016;92:86–96.

    Article  CAS  PubMed  Google Scholar 

  197. Fish JD. Hormone replacement for survivors of childhood cancer with ovarian failure – when is it worth the risk? J Pediatr Adolesc Gynecol. 2011;24:98–101.

    Article  PubMed  Google Scholar 

  198. Crandall CJ, Hovey KM, Andrews CA, et al. Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women’s Health Initiative Observational Study. Menopause. 2018;25(1):11–20.

    Article  PubMed  PubMed Central  Google Scholar 

  199. Mortensen KA, Andersen NH, Gravholt CH. Cardiovascular phenotype in Turner syndrome – integrating cardiology, genetics, and endocrinology. Endocr Rev. 2012;33(5):677–714.

    Article  CAS  PubMed  Google Scholar 

  200. Lucaccioni L, Wong SC, Smyth A, et al. Turner syndrome – issues to consider for transition to adulthood. Br Med Bull. 2015;113(1):45–58.

    Article  CAS  PubMed  Google Scholar 

  201. Gravholt CH, Andersen NH, Conway GS, et al. Proceedings from the 2016 Cincinnati international Turner syndrome meeting. Eur J Endocrinol. 2017;177:G1–G70.

    Article  CAS  PubMed  Google Scholar 

  202. Donato B, Ferreira MJ. Cardiovascular risk in Turner syndrome. Rev Port Cardiol. 2018;37(7):607–21.

    Article  PubMed  Google Scholar 

  203. Dunselman GA, Vermeulen N, Becker C, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29:400–12.

    Article  CAS  PubMed  Google Scholar 

  204. Kaira SK, Gracia CR, Barnhart KT. Symptomatic fibroids in two patients on hormone replacement therapy with primary ovarian failure secondary to prepubertal gonadotoxic cancer treatment. J Womens Health (Larchmt). 2008;17(6):1035–7.

    Article  Google Scholar 

  205. Oparil S. Hormone therapy of premature ovarian failure: the case for “natural” estrogen. Hypertension. 2009;53(5):745–6.

    Article  CAS  PubMed  Google Scholar 

  206. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(11):3975–4011.

    Article  CAS  PubMed  Google Scholar 

  207. Pinkerton JV. Hormone therapy: key points from NAMS 2017 position statement. Clin Obstet Gynecol. 2018;61(3):447–53.

    PubMed  Google Scholar 

  208. Mueck AO, Seeger H. Smoking, estradiol metabolism and hormone replacement therapy. Curr Med Chem Cardiovasc Hematol Agents. 2005;3(1):45–54.

    Article  CAS  PubMed  Google Scholar 

  209. Jandíková H, Dušková M, Šimůnková K, et al. How smoking cessation influences hormonal levels in postmenopausal women. Prague Med Rep. 2014;115(1–2):60–6.

    Article  PubMed  Google Scholar 

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Bruni, V., Pampaloni, F. (2019). Hormone Replacement Therapy in Premature Ovarian Insufficiency. In: Berga, S., Genazzani, A., Naftolin, F., Petraglia, F. (eds) Menstrual Cycle Related Disorders. ISGE Series. Springer, Cham. https://doi.org/10.1007/978-3-030-14358-9_10

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