As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsem*nt of, or agreement with, the contents by NLM or the National Institutes of Health.
Learn more: PMC Disclaimer | PMC Copyright Notice
Ann Med Health Sci Res. 2013 Jan-Mar; 3(1): 90–95.
PMCID: PMC3634232
PMID: 23634337
TC Okeke,1,2 UB Anyaehie,2 and CC Ezenyeaku3
Author information Copyright and License information PMC Disclaimer
Abstract
Premature menopause affects 1% of women under the age of 40 years. The women are at risk of premature death, neurological diseases, psychosexual dysfunction, mood disorders, osteoporosis, ischemic heart disease and infertility. There is need to use simplified protocols and improved techniques in oocyte donation to achieve pregnancy and mother a baby in those women at risk. Review of the pertinent literature on premature menopause, selected references, internet services using the PubMed and Medline databases were included in this review. In the past, pregnancy in women with premature menopause was rare but with recent advancement in oocyte donation, women with premature menopause now have hoped to mother a child. Hormone replacement therapy is beneficial to adverse consequences of premature menopause. Women with premature menopause are at risk of premature death, neurological diseases, psychosexual dysfunction, mood disorders, osteoporosis, ischemic heart disease and infertility. Public enlightenment and education is important tool to save those at risk.
Keywords: Bilateral oophorectomy, Induced menopause, Oestrogen, Ovarian failure, Premature menopause, Spontaneous menopause
Introduction
Premature Menopause is defined as premature ovarian failure before the age of 40 years[1,2] or ovarian failure occurring two standard deviations in years before the mean menopausal age of the study population.[1–3] The first definition is the most commonly accepted definition of premature menopause.[2] It is marked by amenorrhea, increased gonadotrophin levels and oestrogen deficiency. Premature menopause can be spontaneous or induced. Induced premature menopause could be as a result of medical interventions such as chemotherapy or surgical interventions such as bilateral oophorectomy. Regardless of cause, women who experience oestrogen deficiency at an early age before the natural menopause are now recognized to be at increased risk for premature morbidity and mortality.[4]
In the past, little was known about premature menopause until quite recently. It affects approximately 1% of women under the age of 40 years.[5] It is a relatively common condition. The diagnosis should always be considered in any woman presenting with a history of primary or secondary amenorrhea or oligomenorrhoea, vasomotor disturbances or other signs of oestrogen deficiency and may be confirmed by the detection of an elevated serum level of follicle stimulating hormone.
Cessation of menstruation and the development of climacteric symptoms can occur few years after menarche. The causes for premature ovarian failure are unknown. It is most frequently idiopathic but may be due to autoimmune disorders, genetic causes, infections, enzyme deficiencies or metabolic syndromes.[6,7]
In our environment, there is need to enlighten the public on premature menopause and the risk of osteoporosis, ischemic heart disease and associated infertility.
Materials and Methods
We retrieved pertinent literature on premature menopause, selected references, internet services using the PubMed and Medline databases. We conducted a comprehensive literature search of publications related to premature menopause using the keywords ‘premature menopause’, ‘induced menopause’, ‘spontaneous menopause’ ‘ovarian failure’ and ‘bilateral oophorectomy’.
Incidence
Premature menopause affects 1% of all women under the age of 40. It is seen in 10-28% of primary amenorrhea and 4-18% of secondary amenorrhea.[8,9] Premature menopause is however not a rare condition.[10]
Aetiology
The definite aetiology of premature menopause cannot be determined but some causes are identifiable.[3,10,11] These include:
Genetic disorders
Genetic disorders are commoner in those cases that present early.[12] Examples of genetic disorders are chromosomal abnormalities. Ovarian dysgenesis is a major cause of premature menopause. Ovarian dysgenesis is seen in 30% of the cases.[3] Sex chromosome anomalies predominate as a cause. The commonest abnormality is 45X0 (Turner's syndrome). Chromosomal abnormalities are reported in 10-20% of cases involving X sex chromosomes.[3]
Genetic causes of premature menopause:
Examples of Chromosomal abnormalities
-
Turner's syndrome
-
Pure gonadal dysgenesis
-
Familial
-
Trisomy 18 and Trisomy 13
Metabolic
17 alpha-hydroxylase deficiency
Galactosaemia
Myotonic dystrophy
Immunological
Di George syndrome
Ataxia telangiectasia
Mucocutaneous fungal infections
Autoimmune diseases
This is reported in 30-60% of cases.[3] They are the more common causes in the later onset presentations.[11] Autoimmune causes of premature menopause are thyroid diseases, mumps, hyperparathyroidism and Addison's disease. The ovarian biopsy in these conditions show infiltration of the follicles with plasma cells and lymphocytes.[3] Women with autoimmune premature menopause are at increased risk for adrenal insufficiency, hypothyroidism, diabetes mellitus, myasthenia gravis, rheumatoid arthritis and systemic lupus erythematosis.[13,14]
Infections
Mumps is the commonest infection associated with premature menopause. Its effect is maximal during the fetal and pubertal periods when even subclinical infection can result in ovarian failure.[15] Pelvic tuberculosis can cause secondary amenorrhea and ovarian failure. Pelvic tuberculosis is seen in 3% of cases.[16] It is important to note that pelvic tuberculosis results in intrauterine synechiae with endometrial destruction more in women suffering from this infection and not ovarian failure.
Smoking
Is known to induce premature menopause. There is a dose-related effect of smoking on age of menopause.[3,17] The effect of smoking is believed to be caused through polycyclic hydrocarbons contained in cigarette smoke.[18] Apart from smoking, early menopause may be associated with poor health, poor nutrition and increased parity.[19]
Iatrogenic
Radiation and chemotherapy can cause premature menopause but the effect is reversible and the ovary may resume ovulation and menstruation after one year of amenorrhea.[3] Megavotlage irradiation (4500-5000 rads) is often associated with ovarian failure but irradiations less than 500 rads restores normal ovarian function by 50% after a period of one year or two and pregnancies have occurred.[3,10] There is no evidence that low dose irradiation (diagnostic or therapeutic doses of radio nuclides) or ultraviolet light or domestic microwave appliances cause significant loss of ovarian function.[20] The chemotherapeutic agents implicated in the aetiology of premature menopause are alkylating agents, methotrexate, 6 mercaptopurine, actimomycin and adriamycin. Ovarian damage from cancer therapy depends on the age at treatment and on the type of treatment. Women that are younger than 40 years are at lower risk for ovarian failure than older women. However, exposure to higher doses of alkylating agents and higher doses of radiation to the ovary are more likely to induce ovarian failure.[21]
Surgery
Ovarian failure following hysterectomy is seen in 15-50% of the cases.[3] This is caused by impairment of ovarian vascular supply or by the loss of some important endocrine contribution by the uterus to the ovary. At surgery, effort must be made to preserve all normal ovarian tissue and prevent damage to the ovarian blood supply.[10] The practice of prophylactic oophorectomy has increased overtime and more than doubled between 1965 and 1990.[22] Bilateral oophorectomy is carried out to prevent ovarian cancer.
Drugs
Prolonged GnRH therapy may lead to ovarian suppression and failure[3]. Others are chemotherapeutic drugs particularly alkylating agents.[23]
Pathophysiology
Lack of gonadotrophin receptors is the underlying cause of nonresponse of follicles and the main cause of this disorder.[3,10]
Clinical features
Premature menopause is associated with multiple symptoms such as vasomotor symptoms (Hot flushes and night sweats), vagin*l symptoms (vagin*l dryness and dyspareunia), urinary symptoms (frequency, urgency, incontinence and atrophic cystitis), sexual dysfunction, and sleep disturbances.[24] Other symptoms are headache, depression, anxiety, irritability, skin atrophy, joint pains, cancer phobia, pseudocyesis and lack of concentration.
The terms hot flush, hot flash and vasomotor symptoms are often used to describe the same condition.[25] Hot flushes occur in 75%[3,25] of cases and tend to be more severe than in natural menopause. Hot flushes are the most common and distressing complaint for which women seeks advice from their physician. Hot flushes are unpredictable in onset, may present with recurrent periods of sudden, explosive, overwhelming uncomfortable sensation of intense heat or flushing that begins on the face or upper part of the neck and then to upper chest. Hot flushes may be associated with palpitations, a feeling of anxiety and red blotching of the skin. Hot flushes last for 2-5 minutes, varying in frequency with some women experiencing episodes multiple times in a day but decrease with the passage of time.[4] Hot flushes have a detrimental effect on a woman's functional ability and quality of life, however, they are not life threatening.[4,25]
Premature menopause may present with atrophic vagin* which reduces the vagin*l secretion, and dry vagin* can cause dyspareunia. Loss of libido adds to sexual dysfunction. There is reduced libido in about 10-20% of the cases.[3] Premature menopause can cause urethral caruncle, dysuria, with or without infection, urge and stress incontinence.
There is characteristics loss of vagin*l rugae, shortening and narrowing of the vagin*. There is an overall loss of mucosal elasticity with reduced vagin*l secretons and loss of vagin*l transudate. The reduced vagin*l secretions and the delayed timing of vagin*l lubrication during sexual intercourse significantly contribute to dyspareunia in women with premature menopause. The reduced levels of oestrogens cause urogenital atrophy and urogenital diaphragm weakness. The atrophic changes in the female lower genital tract, leads to symptoms of dysuria, urethral discomfort and stress incontinence.
Sleep disturbances may be seen in women with severe hot flushes presenting with cognitive or affective disorders resulting from sleep deprivation.
Diagnostic criteria
There are no unique clinical features that establish the diagnosis of premature menopause. The diagnosis is based on a triad of amenorrhea, elevated gonadotrophin levels and signs and symptoms of oestrogen deficiency. The concentrations of gonadotrophins in the premature menopausal range are necessary to establish a diagnosis of ovarian failure but because of the intermittent presentation of the disease, repeated assays may be required at intervals of 2-4 weeks.[10] Women with FSH levels above 40 mIU/ml may not have viable ovarian follicles on biopsy and such women may be regarded as having undergone permanent ovarian failure.[26]
Investigations
FSH level >40 Miu/ml: E2 level <20 pg/ml.
Chromosomal study: Sex chromosomal analysis should be performed on all patients who present with primary amenorrhea or with early-onset ovarian failure. Buccal smears should be avoided as X and Y chromatin tests are often unreliable for diagnosing sex chromosome abnormalities.[10] The women that present with later onset ovarian failure should have their adrenal reserve checked.
Thyroid function: The women who present with later onset ovarian failure should be screened for high titres of anti-adrenal and anti-thyroid antibodies to rule out autoimmune adrenal or thyroid failure which may follow ovarian failure a year or more later.[10]
Blood Sugar: Blood sugar level should be checked.
X-ray of the pituitary gland to rule out tumor.
Blood calcium level.
Bone mineral density study.
Consequences of premature menopause
The consequences of premature menopause can be divided into short and long term consequences.
Short term consequences include vasomotor symptoms such as hot flushes, night sweats, palpitations and headaches, weight gain, vagin*l dryness and dyspareunia, urgency and stress incontinence with psychological problems including irritability, forgetfulness, insomnia and poor concentration.[3,10,27,28]
The long term consequences of premature menopause include infertility, osteoporosis and an increased risk of premature death, cardiovascular diseases and stroke.[3,10,27,28]
Infertility
It is true that some authors have reported pregnancies in women with premature menopause,[29,30] but the reality is that it is rare. With recent advancement in oocyte donation, women with premature menopause now have hoped to mother a child. Currently, oocyte donation is widely used and it is a successful option in management of infertility due to ovarian failure. The possible theoretical reasons for high pregnancy rates in ovum donation programmes are:
Absence of the state of hypoestrogenism,
Absence of other causes of infertility,
Lack of endometrial hyperstimulation,
Absence of episodes of premature lutenization,
Better control of the window of receptivity.
Osteoporosis
This is a systemic skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in fragility of bone and susceptibility to risk of fracture.[23,31] Women with premature menopause are at increased risk for low bone density, earlier onset osteoporosis and fractures.[32] Maternal aging and oestrogen deficiency as a result of declining ovarian activity have been implicated in the aetiology of osteoporosis.[10,33] Albright, et al.[34] are the first to demonstrate the relationship between oestrogen deficiency, menopause and an increased incidence of fractures in women. Other studies later supported these findings and further demonstrated the beneficial effects of oestrogen replacement therapy.[35,36] Hormone replacement therapy is the corner stone in the prophylaxis and treatment of osteoporosis. The following oestrogen preparations are currently available for management of osteoporosis namely tablets for oral use, creams for percutaneous or vagin*l use, vagin*l rings, transdermal patches and subcutaneous implants. Subcutaneous implants provide a safe simple delivery system for hormone replacement therapy.[37] Implants have little or no adverse effect on clotting factors, blood pressure, or glucose tolerance.[37]
Cardiovascular consequences
Premature menopause is associated with an increased risk of ischemic heart disease and angina and the risk increases with an earlier age of ovarian failure.[10,38] It is also associated with increased cardiovascular mortality and total mortality.[39–41] Oestrogen deficiency increases the risk of ischemic heart disease and angina in a post-menopausal woman. Oestrogen is cardio protective in prevention of cardiovascular disease.[42] Oestrogen also increases HDL and decreases LDL, cholesterol and triglycerides. Oestrogen receptors have been found throughout the cardiovascular system.[43] A typical oestrogen effect is a relaxation in arterial tone and a decrease in resistance.[43]
Management of premature menopause
The most important approach in management of premature menopause is to identify the cause and institute treatment based on the cause. It is now possible to restore follicular maturation, ovulation and menstruation with treatment of identified cause of premature menopause.
With ovulation induction or oocyte donation in IVF programmes, it is possible to achieve pregnancy. Women with primed endometrium using oestrogen, can be followed with progestogen challenge test to demonstrate the possibility of induction of menstruation.
It is good practice to recommend oestrogen replacement therapy for women with premature menopause.[44–46] Women with hypo oestrogenaemia may require hormone replacement therapy (HRT) to avoid osteoporosis. There is some evidence that restoring normal oestrogen levels will reduce the later development of cardiovascular disease, osteoporosis and possibly dementia.[47] Thus, short term use of HRT is considered an option by many.[47–50] Treatment for each woman is considered virtually: Mandatory.[51] It is possible to treat autoimmune disease with corticosteroid therapy if antibodies to sex hormones are present in the blood.
Problems associated with premature menopause
Premature menopause is associated with long term health risks such as premature death, cardiovascular disease, neurologic disease, osteoporosis, and psychosexual dysfunction and mood disorders. Oestrogen mitigates some but not all of these consequences. The use of oestrogen is controversial and problematic because it is the most recognized effective treatment option which is often contraindicated. Premature menopause that result from cancer treatments such as chemotherapy and radiation or from bilateral oophorectomy has increased over time because of the improved success in the treatment of cancer in children, adolescents and reproductive-age women. Furthermore, the practice of prophylactic bilateral oophorectomy at the time of hysterectomy has increased overtime.[22] However, there is strong evidence that long term risks and adverse health outcomes following induced menopause is increasing.[22] Serious health consequences such as premature death, cardiovascular and neurologic disease, osteoporosis, psychiatric symptoms and impaired sexual function are linked with induced menopause.[22]
Women with premature menopause are at risk for low bone density, earlier onset osteoporosis and fractures,[32] earlier onset of coronary heart disease and increased cardiovascular mortality.[39] Women with premature ovarian failure have been reported to have diminished general and sexual well-being and are less satisfied with their sexual lives.[52] Furthermore, women with premature ovarian failure have more anxiety, depression, somatization, sensitivity, hostility and psychological distress than women with normal ovaries.[52]
Conclusion
Women with premature menopause are at risk of premature death, osteoporosis, ischemic heart disease, angina and infertility.[53] This condition is common in our environment affecting 1% of women under the age of 40 years. Public enlightenment and education is important tool to save those at risk. With simplified protocols and improved techniques the affected women may achieve pregnancy and mother a baby.
Footnotes
Source of Support: Nil.
Conflict of Interest: None declared.
References
1. Laughlin D, Thorney Croft IH. Amenorrhea. In: DeCherney AH, Nathan L, editors. Current obstetric and gynecologic diagnosis and treatment. 9th edition. New York: McGraw Hill Companies; 2003. pp. 991–1000. [Google Scholar]
2. Jewelwicz R, Schwartz M. Premature ovarian failure. Bull N Y Acad Med. 1986;62:219–36. [PMC free article] [PubMed] [Google Scholar]
3. Padubidri VG, Daftary SN, editors. Shaw's Textbook of Gynecology. 13th edition. New Delhi: Elsevier; 2004. Menopause, premature menopause and post menopausal bleeding; pp. 56–67. [Google Scholar]
4. Ikeme ACC, Okeke TC, Akogu SPO, Chinwuba N. Knowledge and perception of menopause and climacteric symptoms among a population of women in Enugu, South East, Nigeria. Ann Med Health Sci Res. 2011;1:31–6. [PMC free article] [PubMed] [Google Scholar]
5. Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. 1986;67:604–6. [PubMed] [Google Scholar]
6. Menopause Practice: A Clinician's Guide. 3rd ed. Cleveland, OH: North American Menopause Society; 2007. North American Menopause Society. [Google Scholar]
7. Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009;360:606–14. [PMC free article] [PubMed] [Google Scholar]
8. Russell P, Bannatyne P, Shearman RP, Fraser I, Corbertt P. Premature hyper-gonadotropic ovarian failure. Clinico-pathological study of 19 cases. Int J Gynecol Pathol. 1982;1:185–201. [PubMed] [Google Scholar]
9. Mashchak CA, Kletzky OA, Davajan V, Mishell DR., Jr Clinical and Laboratory evaluation of patients with primary amenorrhea. Obstet Gynecol. 1981;57:715–21. [PubMed] [Google Scholar]
10. Baber R, Abdalla H, Studd F. The premature menopause. In: Studd J, editor. Progress in Obstetrics and Gynecology. Vol. 9. Edinburgh: Churchill Livingstone; 1991. pp. 209–26. [Google Scholar]
11. Ke RW. Management of menopause. In: Ling FW, Diff P, editors. Obstetrics and Gynecology Principles of Practice. 1st edition. New York: McGraw-Hill Companies; 2001. pp. 1021–40. [Google Scholar]
12. Alper MM, Gamer PR. Premature ovarian failure. Its relationship to autoimmune disease. Obstet Gynecol. 1985;66:27–30. [PubMed] [Google Scholar]
13. Panay N, Kalu E. Management of premature ovarian failure. Best Pract Res Clin Obstet Gynaecol. 2009;23:129–40. [PubMed] [Google Scholar]
14. Hoek A, Schoemaker J, Drexhage HA. Premature ovarian failure and ovarian autoimmunity. Endocr Rev. 1997;18:107–34. [PubMed] [Google Scholar]
15. Morrison JC, Gimes JR, Wiser LW, Fish SA. Mumps oophoritis: A cause of premature menpause. Fertil Steril. 1975;26:655–9. [PubMed] [Google Scholar]
16. Nogales-Ortiz F, Tarncon I, Nogales FF. The pathology of female genital tuberculosis. Obstet Gynecol. 1979;53:422–8. [PubMed] [Google Scholar]
17. Jick A, Porter J, Morrison AS. The relationship between smoking and age of natural menopause. Lancet. 1977;ii:1354. [PubMed] [Google Scholar]
18. Gulips BJ, Mattison DR. Degeneration of mouse oocytes in response to polycystic aromatic hydrocarbons. Anat Rec. 1979;193:863–4. [PubMed] [Google Scholar]
19. Mahadevan K, Murthy M, Reddy P, BhasKaran S. Early menopause and its determinants. J Biosoc Sci. 1982;14:473–6. [PubMed] [Google Scholar]
20. Verp MS. Environmental causes of ovarian failure. Semin Reprod Endocrinol. 1983;1:101–11. [Google Scholar]
21. Sklar C. Maintenance of ovarian function and risk of premature menopause related to cancer treatment. J Natl Cancer Inst Monogr. 2005:25–7. [PubMed] [Google Scholar]
22. Keshavarz H, Hillis SD, Kieke BA, Marchbanks PA. Surveillance summaries, July 12, 2002. MMWR. 2002;51:1–8. Hysterectomy Surveillance – United States, 1994-1999. [Google Scholar]
23. Jones NL, Judd H. Menopause and post menopause. In: DeCherney AH, Nathan L, editors. Current Obstetric and Gynecologic Diagnosis and Treatment. 9th edition. New York: McGraw-Hills Companies; 2003. pp. 1018–40. [Google Scholar]
24. Burnett A, editor. Clinical Obstetrics and Gynecology: A problem-based Approach. 1st edition. Massachusettes: Blackwell Science Inc; 2001. Menopause; pp. 269–74. [Google Scholar]
25. Neff MJ. The North American Menopause Society (NAMS) Releases position statement on the treatment of vasomotor symptoms associated with menopause. Practice guideline. Am Fam Physician. 2004;70:393–9. [PubMed] [Google Scholar]
26. Goldenberg RL, Grodin JM, Rodbard D, Ross GT. Gonadotropins in women with amenorrhoea. Am J Obstet Gynecol. 1973;116:1003–12. [PubMed] [Google Scholar]
27. Ganz PA. Breast cancer, menopause and long-term survivorship: Critical issues for the 21st century. Am J Med. 2005;118:136–41. [PubMed] [Google Scholar]
28. Buijs C, de Vries EG, Mourits MJ, Willemse PH. The influence of endocrine treatments for breast cancer on health-related quality of life. Cancer Treat Rev. 2008;34:640–55. [PubMed] [Google Scholar]
29. Netter A, Cahen G, Rozenbaum H. Le syndrome des ovaries resistant aux gonadotropines. Actual Gynecol. 1977;8:29–38. [Google Scholar]
30. Wright CS, Jacobs HS. Spontaneous pregnancy in a patient with hypergonadotrophic ovarian failure. Br J Obstet Gynaecol. 1979;86:389–92. [PubMed] [Google Scholar]
31. Consensus Development Conference. Prophylaxis and treatment of osteoporosis. Am J Med. 1991;90:107–10. [PubMed] [Google Scholar]
32. Gallagher JC. Effect of early menopause on bone mineral density and fractures. Menopause. 2007;14:567–71. [PubMed] [Google Scholar]
33. McClung MR. The relationship between bone mineral density and fracture risk. Curr Osteoporos Rep. 2005;3:57–63. [PubMed] [Google Scholar]
34. Albright F, Smith P, Richardson AM. Post menopausal osteoporosis: Its clinical features. JAMA. 1941;116:2465–74. [Google Scholar]
35. Lindsay R, Aitken J, Anderson J, Hart D, MacDonald E, Clarke AC. Long term prevention of post-menopusal osteoporosis by oestrogen. Lancet. 1976;1:1038–41. [PubMed] [Google Scholar]
36. Christiansen C, Christiansen M, Transbol I. Bone mass in post-menopausal women after withdrawal of oestrogen/gestogen replacement therapy. Lancet. 1981;1:459–61. [PubMed] [Google Scholar]
37. Studd JWW, Magos A. Hormone pellet implantation for the menopause and premenstrual tension. Obstet Gynecol Clin North Am. 1987;14:229–49. [PubMed] [Google Scholar]
38. Lokkegaard E, Jovanovic Z, Heitmann BL, Keiding N, Ottesen B, Pedersen AT. The association between early menopause and risk of ischaemic heart disease: Influence of hormone therapy. Maturitas. 2006;53:226–33. [PubMed] [Google Scholar]
39. Mondul AM, Rodriguez C, Jacobs EJ, Calle EE. Age at natural menopause and cause-specific mortality. Am J Epidemiol. 2005;162:1089–97. [PubMed] [Google Scholar]
40. Jacobsen BK, Heuch I, Kvale G. Age at natural menopause and all-cause mortality: A 37-year follow-up of 19,731 Norwegian women. Am J Epidemiol. 2003;157:23–9. [PubMed] [Google Scholar]
41. Rivera CM, Grossardt BR, Rhodes DJ, Brown RD, Jr, Roger VL, Melton LJ, 3rd, et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause. 2009;16:15–23. [PMC free article] [PubMed] [Google Scholar]
42. Grodstein F, Manson JE, Colditz GA, Willett WC, Speizer FE, Stampfer MJ. A prospective observational study of post-menopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med. 2000;133:933–41. [PubMed] [Google Scholar]
43. Cust M. Menopause. In: Arulkumaran S, Symonds IM, Fowlie A, editors. Oxford Handbook of Obstetrics and Gynecology. 1st edition. New Delhi: Oxford University Press; 2004. pp. 665–9. [Google Scholar]
44. Pines A, Sturdee WD, Birkhauser MH, Schneider HP, Gambacciani M, et al. IMS updated recommendations on post-menopausal hormone therapy. Climacteric. 2007;10:181–94. Board of the international menopause S. [PubMed] [Google Scholar]
45. Pitkin J, Rees MC, Gray S, Lumsden MA, Marsden J, Stevenson JC, et al. Management of premature menopause. Menopause Int. 2007;13:44–5. [PubMed] [Google Scholar]
46. Utian WH, Archer DF, Bachmann GA, Gallagher C, Grodstein F, Heiman JR, et al. Estrogen and progestogen use in post-menopausal women: July 2008 position statement of The North American Menopause Society. Menopause. 2008;15:584–602. [PMC free article] [PubMed] [Google Scholar]
47. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101:80–7. [PMC free article] [PubMed] [Google Scholar]
48. Writing Group for the Women's Health Initiative. Risks and benefits of oestrogen plus progestin in healthy postmenopausal women: Principal results from the women's health initiative randomized control trial. JAMA. 2002;288:321–33. [PubMed] [Google Scholar]
49. Whitehead M, Studd JW. Selection of patients for treatment: Which therapy and for how long? In: Studd JWW, Whitehead MI, editors. The Menopause. Oxford: Blackwell Science; 1988. p. 117. [Google Scholar]
50. Whitehead M, Godfree V. Hormone replacement therapy: Your questions answered. Edinburgh: Churchil Livingstone; 1992. [Google Scholar]
51. Cust M. Hormone replacement therapy. In: Arulkumaran S, Symonds IM, Fowlie A, editors. Oxford handbook of Obstetrics and Gynecology. 1st edition. New Delhi: Oxford University Press; 2004. pp. 671–5. [Google Scholar]
52. van der Stege JG, Groen H, van Zadelhoff SJ, Lambalk CB, Braat DD, van Kasteren YM, et al. Decreased androgen concentrations and diminished general and sexual well-being in women with premature ovarian failure. Menopause. 2008;15:23–31. [PubMed] [Google Scholar]
53. Whitehead MI. Menopause. In: Edmonds DK, editor. Dewhurst's Textbook of Obstetrics and Gynecology for Post Graduate. Sixth edition. Oxford: Blackwell Science; 1991. pp. 441–61. [Google Scholar]
Articles from Annals of Medical and Health Sciences Research are provided here courtesy of Wolters Kluwer -- Medknow Publications
