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premature ovarian failure (premenopausal anovulation)

Cessation of ovarian function under the age of 40 years Etiology: 1) chemotherapy induced ovarian failure in survivors of childhood malignancies, especially alkylating agents 2) autoimmune disease a) Addison's disease b) hypoparathyroidism c) thyroid antibodies (Hashimoto's thyroiditis) d) Schmidt's syndrome e) systemic lupus erythematosus f) myasthenia gravis [11] 3) genetic forms (see genetics) Epidemiology: - accounts for 10-20% of women with amenorrhea Genetics: 1) deletions in the long arm of chromosome X 2) associated with defects in FOXL2 gene (POF3) 3) associated with defects in POF1B (POF2B) 4) associated with defects in DIAPH2 (type 2A) 5) associated with defects in GDF9B (BMP15) (type 4) [2] 6) associated with isoform CSB-PGBD3 of the chimeric protein ERCC6-PGBD3 Clinical manifestations: 1) amenorrhea a) before age 40 b) may be intermittent in early phases 2) hot flashes 3) breast tenderness 4) hypoestrogenism 5) early menopause Laboratory: - elevated levels of serum FSH, serum LH - isolated increases in serum FSH in early phases - serum estradiol is low Management: 1) estrogen replacement (hormone replacement therapy) a) may be indicated for women with permanent ovarian failure b) NOT a reliable contraceptive c) NOT useful for fertility treatment d) chemotherapy-induced premature ovarian failure is not a contraindication [1] 2) 10 mg medroxyprogesterone acetate for 10 days every other month to prevent endometrial hyperplasia

Related

ovary

General

amenorrhea (oligomenorrhea) reproductive failure

Database Correlations

OMIM correlations

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 17, 19. American College of Physicians, Philadelphia 1998, 2015, 2023
  2. OMIM :accession 300510
  3. Cordts EB, Christofolini DM, Dos Santos AA et al Genetic aspects of premature ovarian failure: a literature review. Arch Gynecol Obstet. 2011 Mar;283(3):635-43 PMID: 21188402
  4. Bakalov VK, Vanderhoof VH, Bondy CA, Nelson LM. Adrenal antibodies detect asymptomatic auto-immune adrenal insufficiency in young women with spontaneous premature ovarian failure. Hum Reprod. 2002 Aug;17(8):2096-100. PMID: 12151443 Free Article
  5. Belvisi L, Bombelli F, Sironi L, Doldi N. Organ-specific autoimmunity in patients with premature ovarian failure. J Endocrinol Invest. 1993 Dec;16(11):889-92. PMID: 8144865
  6. de Moraes Ruehsen M, Blizzard RM, Garcia-Bunuel R, Jones GS. Autoimmunity and ovarian failure. Am J Obstet Gynecol. 1972 Mar;112(5):693-703. PMID: 4551032
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  9. Mignot MH, Schoemaker J, Kleingeld M, Rao BR, Drexhage HA. Premature ovarian failure. I: The association with autoimmunity. Eur J Obstet Gynecol Reprod Biol. 1989 Jan;30(1):59-66. PMID: 2647538 - Mignot MH, Drexhage HA, Kleingeld M et al Premature ovarian failure. II: Considerations of cellular immunity defects. Eur J Obstet Gynecol Reprod Biol. 1989 Jan;30(1):67-72. PMID: 2647539
  10. Moncayo-Naveda H, Moncayo R, Benz R, Wolf A, Lauritzen C. Organ-specific antibodies against ovary in patients with systemic lupus erythematosus. Am J Obstet Gynecol. 1989 May;160(5 Pt 1):1227-9. PMID: 2729399
  11. Ryan MM, Jones HR Jr. Myasthenia gravis and premature ovarian failure. Muscle Nerve. 2004 Aug;30(2):231-3. PMID: 15266640
  12. Clines GA. Mechanisms and treatment of hypercalcemia of malignancy. Curr Opin Endocrinol Diabetes Obes. 2011 Dec;18(6):339-46. Review. PMID: 2189722
  13. Legrand SB. Modern management of malignant hypercalcemia. Am J Hosp Palliat Care. 2011 Nov;28(7):515-7. Review. PMID: 21724679