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Premature ovarian failure

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    Premature ovarian failure Premature ovarian failure Presentation Transcript

    • Dr Surveen Ghumman MD Specialist Vardhaman Mahavir Medical College & Safdarjang Hospital, Delhi
      • 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.
      • 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
      • Induced (iatrogenic) POF/POI
      • Spontaneous POF/POI – Cause usually unknown
      • Two Mechanisms
      Follicular Depletion Decreased germ cell migration Accelerated atretic process Acquired ovarian disease Follicular Dysfunction
    • GENETIC AUTOIMMUNE ENVIRONMENTAL IATROGENIC IDIOPATHIC INFECTIOUS ETIOLOGY
      • Irradiation
      • Chemotherapy
      • Occupational exposure
      • Pelvic surgery
      • Smoking
      • Increased use of gonadotrophic stimulation
      • 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
      • 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)
          • 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
          • 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
        • Tests to establish the diagnosis of POF/POI,
        • Tests that help clarify the etiology,
        • Screening tests for other diseases known to have higher prevalence among women with POF/POI.
        • 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
            • 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)
      • 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
        • 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
        • 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
        • 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
        • 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
      • 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.
      • 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.
      • 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
      • 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).
      • 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.
      • Thank You
      • DR.Maninder Ahuja
      • Chairperson Geriatric Gynecology committee
      • Author :
      • Dr.surveen Ghuman
      • Thanks to all those who would carry this torch further.