premature ovarian failure
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Dr Surveen Ghumman MDSpecialist
Vardhaman Mahavir Medical College & Safdarjang Hospital, Delhi
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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.
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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
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1. Induced (iatrogenic) POF/POI 2. Spontaneous POF/POI – Cause usually
unknown
Two Mechanisms
Follicular DepletionDecreased germ cell migrationAccelerated atretic processAcquired ovarian disease
Follicular Dysfunction
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GENETIC
AUTOIMMUNEENVIRONMENT
AL
IATROGENIC
IDIOPATHIC
INFECTIOUS
ETIOLOGY
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Irradiation Chemotherapy Occupational exposure Pelvic surgery Smoking Increased use of gonadotrophic
stimulation
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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
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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)
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Last spontaneous menstrual cycle Prior pelvic surgeries, irradiation, or chemotherapy Symptoms of adrenal insufficiency:
Orthostatic hypotensionSkin hyperpigmentationUnexplained weaknessSalt cravingAbdominal painAnorexia
Symptoms of hypothyroidism Family history of POF, male mental retardation,
autoimmune disorders Symptoms of estrogen deprivation
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Signs of hypoestrogenism Enlarged ovaries versus nonpalpable ovaries Physical stigmata of Turner syndrome/other genetic
syndromes:Short statureWebbed neckLow position of the earsLow posterior hairlineCubitus valgusShield chestShort IV and V metacarpals
Signs of autoimmune diseases, Addison disease, and hypothyroidism
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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 testFSH , LH, estradiol (FSH value - over 40 mIU/ml on at
least two occasions over a four weeks period)Standard blood chemistry - Fasting glucose, electrolytes,
creatinineKaryotypeTest for fragile X chromosome (FMR1 premutation)Bone density by dual-energy x-ray absorptiometry (DEXA)
scanUSG ovary
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HaemogramESRSe Electrolytes, calcium, phosphate, serum
proteinSerum cortisolANA, rheumatoid factorOvarian antibodyThyroid-stimulating hormone (TSH)Antithyroid peroxidase antibodySerum adrenal antibodiesBlood sugars ( Fasting and postprandial)
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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
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PregnancySecondary ovarian insufficiency/failure due to the following:
Eating disorderExtreme physical exerciseProlactinoma and other conditions causing hyperprolactinemiaPituitary and hypothalamic tumorsHypothalamic and pituitary infiltrative and inflammatory processesPituitary hemorrhage
Systemic diseases, including other endocrine disordersMedicationsHyperandrogenic conditions due to the following:
Polycystic ovarian syndromeCongenital adrenal hyperplasiaOvarian or adrenal androgen-producing tumorsOvarian hyperthecosis
Outflow tract abnormalitiesPseudo premature ovarian failure due to the following:
Gonadotropin-producing pituitary adenomaAntibodies to gonadotropins
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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
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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
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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
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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.
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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.
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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
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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).
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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.
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Thank You
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DR.Maninder AhujaChairperson Geriatric Gynecology
committeeAuthor : Dr.surveen Ghuman Thanks to all those who would carry this
torch further.