Lymphocytic oophoritis with positive adrenal antibodies/Addison disease
Gonadotropin receptor antibodies
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:
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:
Low position of the ears
Low posterior hairline
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
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
Test for fragile X chromosome (FMR1 premutation)
Bone density by dual-energy x-ray absorptiometry (DEXA) scan
Se Electrolytes, calcium, phosphate, serum protein
ANA, rheumatoid factor
Thyroid-stimulating hormone (TSH)
Antithyroid peroxidase antibody
Serum adrenal antibodies
Blood sugars ( Fasting and postprandial)
Vascular symptoms like hot flushes, night sweats,
Urgency and stress urinary incontinence
Psychological Impact - Depression
Secondary ovarian insufficiency/failure due to the following:
Extreme physical exercise
Prolactinoma and other conditions causing hyperprolactinemia
Pituitary and hypothalamic tumors
Hypothalamic and pituitary infiltrative and inflammatory processes
Systemic diseases, including other endocrine disorders
Hyperandrogenic conditions due to the following:
Polycystic ovarian syndrome
Congenital adrenal hyperplasia
Ovarian or adrenal androgen-producing tumors
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 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
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.
13% have levels below normal. Given for short periods.
Androgen replacement could be carefully considered for women with
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
Ovarian cryopreservation in Iatrogenic POF
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.
Elemental Calcium : 1200-1500 mg day.
Adequate intake of vitamin D.
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
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.
Chairperson Geriatric Gynecology committee
Thanks to all those who would carry this torch further.