Dr Surveen Ghumman MD
Vardhaman Mahavir Medical College & Safdarjang
Premature ovarian failure ( POF)
Primary ovarian insufficiency
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
1. Induced (iatrogenic) POF/POI
2. Spontaneous POF/POI – Cause usually
Decreased germ cell migration
Accelerated atretic process
Acquired ovarian disease
Increased use of gonadotrophic stimulation
Ovarian follicle depletion
Low initial follicle number
Pure gonadal dysgenesis
Accelerated follicle atresia
X chromosome related (Turner syndrome, X chromosome deletions
Fragile mental retardation 1 (FMR1) gene premutation
Last spontaneous menstrual cycle
Prior pelvic surgeries, irradiation, or chemotherapy
Symptoms of adrenal insufficiency:
Symptoms of hypothyroidism
Family history of POF, male mental retardation,
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
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
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,
Test for fragile X chromosome (FMR1 premutation)
Bone density by dual-energy x-ray absorptiometry (DEXA) scan
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
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
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
Unproven treatments to restore fertility should
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
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
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.