Early Menopause: Primary Ovarian Insufficiency and Surgical Menopause

ABSTRACT

Early menopause, whether a consequence of primary ovarian insufficiency or resulting from surgical removal of gonads in a premenopausal woman, offers unique health-related challenges. Premature deprivation of sex steroids sets into motion a cascade of events that preferentially target urogenital, skeletal, cardiovascular, and neurocognitive systems, and culminate in global health deterioration in a chronologically younger population of women compared with those undergoing age-appropriate, natural menopause. Overtly, menopausal symptoms may be shared between those experiencing early menopause versus those undergoing a natural attrition of their reproductive physiology. Extrapolation of concerns emanating from recent randomized trials of menopausal hormone therapy may not be applicable to young women experiencing early menopause, however, and estrogen replacement remains a mainstay in the clinical management of this population.

KEYWORDS

primary ovarian insufficiency - surgical menopause - hormone therapy

REFERENCES

• 1 van Noord P A, Dubas J S, Dorland M, Boersma H, te Velde E. Age at natural menopause in a population-based screening cohort: the role of menarche, fecundity, and lifestyle factors.  Fertil Steril. 1997;  68(1) 95-102
• 2 Kalantaridou S N, Nelson L M. Premature ovarian failure is not premature menopause.  Ann N Y Acad Sci. 2000;  900 393-402
• 3 Nelson L, Anasti J N, Kimzey L M. Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure.  J Clin Endocrinol Metab. 1994;  79 1470-1475
• 4 Alper M M, Jolly E E, Garner P R. Pregnancies after premature ovarian failure.  Obstet Gynecol. 1986;  67(3, Suppl) 59S-62S
• 5 Rebar R W, Connolly H V. Clinical features of young women with hypergonadotropic amenorrhea.  Fertil Steril. 1990;  53(5) 804-810
• 6 Rebar R W. Premature ovarian failure.  Obstet Gynecol. 2009;  113(6) 1355-1363
• 7 Albright F, Smith P H, Fraser R. A syndrome characterized by primary ovarian insufficiency.  Am J Med Sci. 1942;  204 625-648
• 8 Welt C K. Primary ovarian insufficiency: a more accurate term for premature ovarian failure.  Clin Endocrinol (Oxf). 2008;  68(4) 499-509
• 9 Nelson L M. Clinical practice. Primary ovarian insufficiency.  N Engl J Med. 2009;  360(6) 606-614
• 10 Coulam C B, Adamson S C, Annegers J F. Incidence of premature ovarian failure.  Obstet Gynecol. 1986;  67(4) 604-606
• 11 Sklar C A, Mertens A C, Mitby P et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study.  J Natl Cancer Inst. 2006;  98(13) 890-896
• 12 Panay N, Fenton A. Premature ovarian failure: a growing concern.  Climacteric. 2008;  11(1) 1-3
• 13 Singh R P, Carr D H. The anatomy and histology of XO human embryos and fetuses.  Anat Rec. 1966;  155(3) 369-383
• 14 Cunniff C, Jones K L, Benirschke K. Ovarian dysgenesis in individuals with chromosomal abnormalities.  Hum Genet. 1991;  86(6) 552-556
• 15 Modi D N, Sane S, Bhartiya D. Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads.  Mol Hum Reprod. 2003;  9(4) 219-225
• 16 Bannatyne P, Russell P, Shearman R P. Autoimmune oophoritis: a clinicopathologic assessment of 12 cases.  Int J Gynecol Pathol. 1990;  9(3) 191-207
• 17 Sedmak D D, Hart W R, Tubbs R R. Autoimmune oophoritis: a histopathologic study of involved ovaries with immunologic characterization of the mononuclear cell infiltrate.  Int J Gynecol Pathol. 1987;  6(1) 73-81
• 18 Morrison J C, Givens J R, Wiser W L, Fish S A. Mumps oophoritis: a cause of premature menopause.  Fertil Steril. 1975;  26(7) 655-659
• 19 Panay N, Kalu E. Management of premature ovarian failure.  Best Pract Res Clin Obstet Gynaecol. 2009;  23(1) 129-140
• 20 Farhi J, Homburg R, Ferber A, Orvieto R, Ben Rafael Z. Non-response to ovarian stimulation in normogonadotrophic, normogonadal women: a clinical sign of impending onset of ovarian failure pre-empting the rise in basal follicle stimulating hormone levels.  Hum Reprod. 1997;  12(2) 241-243
• 21 Broekmans F J, Kwee J, Hendriks D J, Mol B W, Lambalk C B. A systematic review of tests predicting ovarian reserve and IVF outcome.  Hum Reprod Update. 2006;  12(6) 685-718
• 22 Kalantaridou S N, Davis S R, Nelson L M. Premature ovarian failure.  Endocrinol Metab Clin North Am. 1998;  27(4) 989-1006
• 23 Alper M M, Garner P R, Seibel M M. Premature ovarian failure. Current concepts.  J Reprod Med. 1986;  31(8) 699-708
• 24 Alzubaidi N H, Chapin H L, Vanderhoof V H, Calis K A, Nelson L M. Meeting the needs of young women with secondary amenorrhea and spontaneous premature ovarian failure.  Obstet Gynecol. 2002;  99(5 Pt 1) 720-725
• 25 Tibiletti M G, Testa G, Vegetti W et al. The idiopathic forms of premature menopause and early menopause show the same genetic pattern.  Hum Reprod. 1999;  14(11) 2731-2734
• 26 Rebar R W, Erickson G F, Yen S SC. Idiopathic premature ovarian failure: clinical and endocrine characteristics.  Fertil Steril. 1982;  37(1) 35-41
• 27 Manuel M, Katayama P K, Jones Jr H W. The age of occurrence of gonadal tumors in intersex patients with a Y chromosome.  Am J Obstet Gynecol. 1976;  124(3) 293-300
• 28 Sherman S L. Premature ovarian failure in the fragile X syndrome.  Am J Med Genet. 2000;  97(3) 189-194
• 29 Fu Y H, Kuhl D P, Pizzuti A et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox.  Cell. 1991;  67(6) 1047-1058
• 30 Oberlé I, Rousseau F, Heitz D et al. Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome.  Science. 1991;  252 1097-1102
• 31 Verkerk A J, Pieretti M, Sutcliffe J S et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome.  Cell. 1991;  65(5) 905-914
• 32 van Kasteren Y M, Hundscheid R D, Smits A P, Cremers F P, van Zonneveld P, Braat D D. Familial idiopathic premature ovarian failure: an overrated and underestimated genetic disease?.  Hum Reprod. 1999;  14(10) 2455-2459
• 33 LaBarbera A R, Miller M M, Ober C, Rebar R W. Autoimmune etiology in premature ovarian failure.  Am J Reprod Immunol Microbiol. 1988;  16(3) 115-122
• 34 Kim T J, Anasti J N, Flack M R, Kimzey L M, Defensor R A, Nelson L M. Routine endocrine screening for patients with karyotypically normal spontaneous premature ovarian failure.  Obstet Gynecol. 1997;  89(5 Pt 1) 777-779
• 35 Ahonen P, Koskimies S, Lokki M L, Tiilikainen A, Perheentupa J. The expression of autoimmune polyglandular disease type I appears associated with several HLA-A antigens but not with HLA-DR.  J Clin Endocrinol Metab. 1988;  66(6) 1152-1157
• 36 Wheatcroft N, Weetman A P. Is premature ovarian failure an autoimmune disease?.  Autoimmunity. 1997;  25(3) 157-165
• 37 Betterle C, Volpato M, Rees Smith B et al. I. Adrenal cortex and steroid 21-hydroxylase autoantibodies in adult patients with organ-specific autoimmune diseases: markers of low progression to clinical Addison's disease.  J Clin Endocrinol Metab. 1997;  82(3) 932-938
• 38 Keshavarz H, Hillis S D, Kieke B A, Marchbanks P A. Hysterectomy surveillance–United States—1994–1999.  Morb Mortal Wkly Rep CDC Surveillance Summ. 2002;  51 1-8
• 39 Lass A. The fertility potential of women with a single ovary.  Hum Reprod Update. 1999;  5(5) 546-550
• 40 Parker W H, Broder M S, Liu Z, Shoupe D, Farquhar C, Berek J S. Ovarian conservation at the time of hysterectomy for benign disease.  Clin Obstet Gynecol. 2007;  50(2) 354-361
• 41 Rocca W A, Bower J H, Maraganore D M et al. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause.  Neurology. 2007;  69(11) 1074-1083
• 42 Ozdemir S, Celik C, Görkemli H, Kiyici A, Kaya B. Compared effects of surgical and natural menopause on climacteric symptoms, osteoporosis, and metabolic syndrome.  Int J Gynaecol Obstet. 2009;  106(1) 57-61
• 43 Gallagher J C. Effect of early menopause on bone mineral density and fractures.  Menopause. 2007;  14(3 Pt 2) 567-571
• 44 Jacobsen B K, Knutsen S F, Fraser G E. Age at natural menopause and total mortality and mortality from ischemic heart disease: the Adventist Health Study.  J Clin Epidemiol. 1999;  52(4) 303-307
• 45 de Kleijn M J, van der Schouw Y T, Verbeek A L, Peeters P H, Banga J D, van der Graaf Y. Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women.  Am J Epidemiol. 2002;  155(4) 339-345
• 46 Mondul A M, Rodriguez C, Jacobs E J, Calle E E. Age at natural menopause and cause-specific mortality.  Am J Epidemiol. 2005;  162(11) 1089-1097
• 47 Cummings S R, Browner W S, Bauer D Study of Osteoporotic Fractures Research Group et al. Endogenous hormones and the risk of hip and vertebral fractures among older women.  N Engl J Med. 1998;  339(11) 733-738
• 48 Pansini F, Bagni B, Bonaccorsi G et al. Oophorectomy and spine bone density: evidence of a higher rate of bone loss in surgical compared with spontaneous menopause.  Menopause. 1995;  2 109-115
• 49 Aitken J M, Hart D M, Anderson J B, Lindsay R, Smith D A, Speirs C F. Osteoporosis after oophorectomy for non-malignant disease in premenopausal women.  BMJ. 1973;  2(5862) 325-328
• 50 Gambacciani M, Spinetti A, de Simone L et al. The relative contributions of menopause and aging to postmenopausal vertebral osteopenia.  J Clin Endocrinol Metab. 1993;  77(5) 1148-1151
• 51 Gärdsell P, Johnell O, Nilsson B E. The predictive value of bone loss for fragility fractures in women: a longitudinal study over 15 years.  Calcif Tissue Int. 1991;  49(2) 90-94
• 52 Tuppurainen M, Kröger H, Honkanen R et al. Risks of perimenopausal fractures—a prospective population-based study.  Acta Obstet Gynecol Scand. 1995;  74(8) 624-628
• 53 van der Klift M, de Laet C E, McCloskey E V et al. Risk factors for incident vertebral fractures in men and women: the Rotterdam Study.  J Bone Miner Res. 2004;  19(7) 1172-1180
• 54 Ross R. Atherosclerosis—an inflammatory disease.  N Engl J Med. 1999;  340(2) 115-126
• 55 Bush D E, Jones C E, Bass K M, Walters G K, Bruza J M, Ouyang P. Estrogen replacement reverses endothelial dysfunction in postmenopausal women.  Am J Med. 1998;  104(6) 552-558
• 56 de Kleijn M J, Wilmink H W, Bots M L et al. Hormone replacement therapy and endothelial function. Results of a randomized controlled trial in healthy postmenopausal women.  Atherosclerosis. 2001;  159(2) 357-365
• 57 Virdis A, Ghiadoni L, Pinto S et al. Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women.  Circulation. 2000;  101(19) 2258-2263
• 58 Kalantaridou S N, Naka K K, Papanikolaou E et al. Impaired endothelial function in young women with premature ovarian failure: normalization with hormone therapy.  J Clin Endocrinol Metab. 2004;  89(8) 3907-3913
• 59 Dørum A, Tonstad S, Liavaag A H, Michelsen T M, Hildrum B, Dahl A A. Bilateral oophorectomy before 50 years of age is significantly associated with the metabolic syndrome and Framingham risk score: a controlled, population-based study (HUNT-2).  Gynecol Oncol. 2008;  109(3) 377-383
• 60 Simoncini T, Hafezi-Moghadam A, Brazil D P, Ley K, Chin W W, Liao J K. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase.  Nature. 2000;  407(6803) 538-541
• 61 Post W S, Goldschmidt-Clermont P J, Wilhide C C et al. Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system.  Cardiovasc Res. 1999;  43(4) 985-991
• 62 Mikkola T S, Clarkson T B. Estrogen replacement therapy, atherosclerosis, and vascular function.  Cardiovasc Res. 2002;  53(3) 605-619
• 63 Phillips L S, Langer R D. Postmenopausal hormone therapy: critical reappraisal and a unified hypothesis.  Fertil Steril. 2005;  83(3) 558-566
• 64 Sack M N, Rader D J, Cannon III R O. Oestrogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women.  Lancet. 1994;  343(8892) 269-270
• 65 Koh K K, Jin D K, Yang S H et al. Vascular effects of synthetic or natural progestagen combined with conjugated equine estrogen in healthy postmenopausal women.  Circulation. 2001;  103(15) 1961-1966
• 66 Bachmann G, Oza D. Female androgen insufficiency.  Obstet Gynecol Clin North Am. 2006;  33(4) 589-598
• 67 Sluijmer A V, Heineman M J, De Jong F H, Evers J L. Endocrine activity of the postmenopausal ovary: the effects of pituitary down-regulation and oophorectomy.  J Clin Endocrinol Metab. 1995;  80(7) 2163-2167
• 68 van der Stege J G, Groen H, van Zadelhoff S J et al. Decreased androgen concentrations and diminished general and sexual well-being in women with premature ovarian failure.  Menopause. 2008;  15(1) 23-31
• 69 Hartmann B W, Kirchengast S, Albrecht A, Laml T, Söregi G, Huber J C. Androgen serum levels in women with premature ovarian failure compared to fertile and menopausal controls.  Gynecol Obstet Invest. 1997;  44(2) 127-131
• 70 Elias A N, Pandian M R, Rojas F J. Serum levels of androstenedione, testosterone and dehydroepiandrosterone sulfate in patients with premature ovarian failure to age-matched menstruating controls.  Gynecol Obstet Invest. 1997;  43(1) 47-48
• 71 Davison S L, Bell R, Donath S, Montalto J G, Davis S R. Androgen levels in adult females: changes with age, menopause, and oophorectomy.  J Clin Endocrinol Metab. 2005;  90(7) 3847-3853
• 72 Løkkegaard E, Jovanovic Z, Heitmann B L, Keiding N, Ottesen B, Pedersen A T. The association between early menopause and risk of ischaemic heart disease: influence of Hormone Therapy.  Maturitas. 2006;  53(2) 226-233
• 73 van Der Voort D J, van Der Weijer P H, Barentsen R. Early menopause: increased fracture risk at older age.  Osteoporos Int. 2003;  14(6) 525-530
• 74 Pouillès J M, Trémollières F, Bonneu M, Ribot C. Influence of early age at menopause on vertebral bone mass.  J Bone Miner Res. 1994;  9(3) 311-315
• 75 Chetkowski R J, Meldrum D R, Steingold K A et al. Biologic effects of transdermal estradiol.  N Engl J Med. 1986;  314(25) 1615-1620
• 76 Scarabin P Y, Oger E, Plu-Bureau G. Estrogen and Thromboembolism Risk Study Group . Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk.  Lancet. 2003;  362(9382) 428-432
• 77 Straczek C, Oger E, Yon de Jonage-Canonico M B Estrogen and Thromboembolism Risk (ESTHER) Study Group et al. Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration.  Circulation. 2005;  112(22) 3495-3500
• 78 Scarabin P Y, Alhenc-Gelas M, Plu-Bureau G, Taisne P, Agher R, Aiach M. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial.  Arterioscler Thromb Vasc Biol. 1997;  17(11) 3071-3078
• 79 Conard J, Samama M, Basdevant A, Guy-Grand B, de Lignières B. Differential AT III-response to oral and parenteral administration of 17 beta-estradiol.  Thromb Haemost. 1983;  49(3) 252
• 80 Høibraaten E, Mowinckel M C, de Ronde H, Bertina R M, Sandset P M. Hormone replacement therapy and acquired resistance to activated protein C: results of a randomized, double-blind, placebo-controlled trial.  Br J Haematol. 2001;  115(2) 415-420
• 81 Mashchak C A, Lobo R A, Dozono-Takano R et al. Comparison of pharmacodynamic properties of various estrogen formulations.  Am J Obstet Gynecol. 1982;  144(5) 511-518
• 82 Pike M C, Peters R K, Cozen W et al. Estrogen-progestin replacement therapy and endometrial cancer.  J Natl Cancer Inst. 1997;  89(15) 1110-1116
• 83 de Ziegler D, Ferriani R, Moraes L A, Bulletti C. Vaginal progesterone in menopause: Crinone 4% in cyclical and constant combined regimens.  Hum Reprod. 2000;  15(Suppl 1) 149-158
• 84 Cicinelli E, de Ziegler D, Alfonso R, Nicoletti R, Bellavia M, Colafiglio G. Endometrial effects, bleeding control, and compliance with a new postmenopausal hormone therapy regimen based on transdermal estradiol gel and every-other-day vaginal progesterone in capsules: a 3-year pilot study.  Fertil Steril. 2005;  83(6) 1859-1863
• 85 Shifren J L. The role of androgens in female sexual dysfunction.  Mayo Clin Proc. 2004;  79(4, Suppl) S19-S24
• 86 Davison S L, Davis S R. Androgens in women.  J Steroid Biochem Mol Biol. 2003;  85(2–5) 363-366
• 87 Papalia M A, Davis S R. What is the rationale for androgen therapy for women?.  Treat Endocrinol. 2003;  2(2) 77-84
• 88 Worboys S, Kotsopoulos D, Teede H, McGrath B, Davis S R. Evidence that parenteral testosterone therapy may improve endothelium-dependent and -independent vasodilation in postmenopausal women already receiving estrogen.  J Clin Endocrinol Metab. 2001;  86(1) 158-161
• 89 Dimitrakakis C, Bondy C. Androgens and the breast.  Breast Cancer Res. 2009;  11(5) 212
• 90 Shifren J L, Davis S R, Dennerstein L et al. The role of testosterone therapy in postmenopausal women: position statement of the North American Menopause Society.  Menopause. 2005;  12 497-511
• 91 North American Menopause Society . The role of calcium in peri- and postmenopausal women: 2006 position statement of the North American Menopause Society.  Menopause. 2006;  13(6) 862-877 quiz 878-880
• 92 Rebar R W. Premature ovarian failure. In: Lobo RA Treatment of the Postmenopausal Woman: Basic and Clinical Aspects. Oxford, United Kingdom; Academic Press 2007: 99-109
• 93 Langrish J P, Mills N L, Bath L E et al. Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure.  Hypertension. 2009;  53(5) 805-811
• 94 Karnis M F, Zimon A E, Lalwani S I, Timmreck L S, Klipstein S, Reindollar R H. Risk of death in pregnancy achieved through oocyte donation in patients with Turner syndrome: a national survey.  Fertil Steril. 2003;  80(3) 498-501
• 95 Practice Committee, American Society for Reproductive Medicine . Increased maternal cardiovascular mortality associated with pregnancy in women with Turner syndrome.  Fertil Steril. 2005;  83(4) 1074-1075
• 96 Sermon K, Seneca S, De Rycke M et al. PGD in the lab for triplet repeat diseases—myotonic dystrophy, Huntington's disease and fragile-X syndrome.  Mol Cell Endocrinol. 2001;  183(Suppl 1) S77-S85
• 97 Al Kadri H, Hassan S, Al-Fozan H M, Hajeer A. Hormone therapy for endometriosis and surgical menopause.  Cochrane Database Syst Rev. 2009;  1(1) CD005997