Premature ovarian failure


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Premature ovarian failure

  1. 1. Dr Surveen Ghumman MD Specialist Vardhaman Mahavir Medical College & Safdarjang Hospital, Delhi
  2. 2.  Premature ovarian failure ( POF)  Primary ovarian insufficiency  Premature menopause  Early menopause POF is a condition characterized by amenorrhea, hypoestrogenism, and elevated serum gonadotropin levels in women younger than 40 years.
  3. 3.  1 – 4 % of women  1 case per 1000 women by age 30,  1 case per 250 women by age 35  1 case per 100 women by age 40.  Primary amenorrhea - 10-28% of women  Secondary amenorrhea - 4-18% of women
  4. 4. 1. Induced (iatrogenic) POF/POI 2. Spontaneous POF/POI – Cause usually unknown Two Mechanisms Follicular Depletion Decreased germ cell migration Accelerated atretic process Acquired ovarian disease Follicular Dysfunction
  6. 6.  Irradiation  Chemotherapy  Occupational exposure  Pelvic surgery  Smoking  Increased use of gonadotrophic stimulation
  7. 7. Ovarian follicle depletion  Low initial follicle number  Pure gonadal dysgenesis  Thymic aplasia/hypoplasia  Idiopathic  Accelerated follicle atresia  X chromosome related (Turner syndrome, X chromosome deletions and translocations)  Galactosemia  Fragile mental retardation 1 (FMR1) gene premutation  Viral oophoritis  Autoimmunity  Environmental toxins  Iatrogenic  Idiopathic
  8. 8. Ovarian follicle dysfunction  Steroidogenic enzyme defects  17-alpha-hydroxylase deficiency  17-20-desmolase deficiency  Aromatase enzyme deficiency  Autoimmunity  Lymphocytic oophoritis with positive adrenal antibodies/Addison disease  Gonadotropin receptor antibodies  Signal defects  Abnormal gonadotropin receptor  Abnormality in the G-protein signaling pathway    Specific genetic defects (blepharophimosis-epicanthus-ptosis syndrome)  Idiopathic (resistant ovary syndrome)
  9. 9.  Last spontaneous menstrual cycle  Prior pelvic surgeries, irradiation, or chemotherapy  Symptoms of adrenal insufficiency: Orthostatic hypotension Skin hyperpigmentation Unexplained weakness Salt craving Abdominal pain Anorexia  Symptoms of hypothyroidism  Family history of POF, male mental retardation, autoimmune disorders  Symptoms of estrogen deprivation
  10. 10.  Signs of hypoestrogenism  Enlarged ovaries versus nonpalpable ovaries  Physical stigmata of Turner syndrome/other genetic syndromes: Short stature Webbed neck Low position of the ears Low posterior hairline Cubitus valgus Shield chest Short IV and V metacarpals  Signs of autoimmune diseases, Addison disease, and hypothyroidism
  11. 11. 1. Tests to establish the diagnosis of POF/POI, 2. Tests that help clarify the etiology, 3. Screening tests for other diseases known to have higher prevalence among women with POF/POI. 4. Tests to establish effect of POF Pregnancy test FSH , LH, estradiol (FSH value - over 40 mIU/ml on at least two occasions over a four weeks period) Standard blood chemistry - Fasting glucose, electrolytes, creatinine Karyotype Test for fragile X chromosome (FMR1 premutation) Bone density by dual-energy x-ray absorptiometry (DEXA) scan USG ovary
  12. 12. Haemogram ESR Se Electrolytes, calcium, phosphate, serum protein Serum cortisol ANA, rheumatoid factor Ovarian antibody Thyroid-stimulating hormone (TSH) Antithyroid peroxidase antibody Serum adrenal antibodies Blood sugars ( Fasting and postprandial)
  13. 13. Short term  Vascular symptoms like hot flushes, night sweats,  Headaches  Vaginal dryness  Dyspareunea  Urgency and stress urinary incontinence  Irritability  Forgetfulness  Poor concentration  Insomnia Long term  Infertility  Osteoporosis  Cardiovascular disease  Stroke  Psychological Impact - Depression
  14. 14. Pregnancy Secondary ovarian insufficiency/failure due to the following: Eating disorder Extreme physical exercise Prolactinoma and other conditions causing hyperprolactinemia Pituitary and hypothalamic tumors Hypothalamic and pituitary infiltrative and inflammatory processes Pituitary hemorrhage Systemic diseases, including other endocrine disorders Medications Hyperandrogenic conditions due to the following: Polycystic ovarian syndrome Congenital adrenal hyperplasia Ovarian or adrenal androgen-producing tumors Ovarian hyperthecosis Outflow tract abnormalities Pseudo premature ovarian failure due to the following: Gonadotropin-producing pituitary adenoma Antibodies to gonadotropins
  15. 15. Hormone replacement therapy (HRT)  Cyclical HRT with estrogens and progestins to relieve the symptoms of estrogen deficiency and to maintain bone density. Estrogens  Estrogens can be administered orally or transdermally.  Higher doses than those for post menopausal women may be needed to achieve adequate estrogenization of the vaginal epithelium in young women and help maintain age-appropriate bone density.  The estrogens can be administered continuously or cyclically.  Estrogen replacement therapy does not prevent ovulation and conception in these patients
  16. 16.  Progestins  Cyclically, 10-14 days each month, to prevent endometrial hyperplasia  If an expected withdrawal bleeding is missing, a pregnancy test should be performed. 5-10% chance of spontaneous pregnancy  The recommended regimens  Medroxyprogesterone 10 mg daily for 10-12 days each month or  Micronized progesterone 200 mg daily for 10-12 days each month.  Androgens  13% have levels below normal.Given for short periods.  Androgen replacement could be carefully considered for women with  Addisons disease  Persistent fatigue,  Low libido,  Poor well being despite adequate estrogen replacement  Available medications include oral methyl testosterone 1.25-2.5 mg/d, injectable testosterone esters 50 mg every 6 weeks intramuscularly, testosterone implants
  17. 17.  Steroids for autoimmune POF not indicated as high doses needed lead to side effects like osteonecrosis.  Unproven treatments to restore fertility should be avoided  Gonadotropin therapy carries a theoretical risk of exacerbating autoimmune POF  ART  Oocyte donation  Embryo adoption  Surrogacy  Ovarian cryopreservation in Iatrogenic POF  Adoption
  18. 18.  Endocrinologist consultation may be indicated for hypothyroidism or adrenal insufficiency.  Psychological evaluation and counseling.  Genetic counseling may be needed in some.  Referral for eye care if symptoms of dry eye.
  19. 19. Diet  Elemental Calcium : 1200-1500 mg day.  Adequate intake of vitamin D. Activity  Weight-bearing exercises for 30 minutes per day, at least 3 days per week, to improve muscle strength and maintain bone mass.  Participation in outdoor sports is strongly recommended.
  20. 20.  Women with POF/POI should be educated on the nature of their disease and the current research efforts. The mere understanding of the problem helps patients cope better.  Support Web sites are available – - International Premature Ovarian Failure Association
  21. 21.  Annual followup to  Monitor HRT.  Symptoms and signs of thyroid disease and adrenal insufficiency .  TSH levels - checked every 3-5 years (every year if antiperoxidase antibody test is positive).  Adrenal antibodies positive on her initial evaluation, even if all adrenal function tests normal - annual ACTH stimulation test.  Adrenal antibody tests negative still continue to carry higher than normal risk for adrenal insufficiency - adrenal antibody test performed every 3-5 years.  Patients with secondary ovarian failure should be monitored for manifestations of the underlying hypothalamic/pituitary pathology (progression of space-occupying lesions and development/progression of hypopituitarism).
  22. 22. POF is a challenging issue as women are delaying having families and this emotionally distressing problem must be dealt, on both the physical and psychological platform.
  23. 23. Thank You
  24. 24.  DR.Maninder Ahuja Chairperson Geriatric Gynecology committee Author :  Dr.surveen Ghuman  Thanks to all those who would carry this torch further.