This document summarizes information about premature ovarian failure (POF). It defines POF as amenorrhea, hypoestrogenism, and elevated gonadotropins in women under age 40. POF prevalence is 1-4% under age 40, increasing to 1% by age 30 and 4% by age 40. Causes include genetic factors, autoimmunity, environmental exposures, infections, and iatrogenic factors. Symptoms include menopausal symptoms and long term risks of osteoporosis and cardiovascular disease. Diagnosis involves lab tests of hormones and imaging. Treatment is hormone replacement therapy. Annual follow up is needed to monitor treatment and screen for other related conditions.

1. Dr Surveen Ghumman MD
Specialist
Vardhaman Mahavir Medical College & Safdarjang
Hospital, Delhi

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.  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. 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

5. GENETIC
AUTOIMMUNE
ENVIRONMENTA
L
IATROGENIC IDIOPATHIC
INFECTIOUSETIOLOGY

6.  Irradiation
 Chemotherapy
 Occupational exposure
 Pelvic surgery
 Smoking
 Increased use of gonadotrophic stimulation

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. 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.  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.  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. 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. 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. 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. 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. 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.  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.  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.  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. 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.  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.  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. 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. Thank You

24.  DR.Maninder Ahuja
Chairperson Geriatric Gynecology committee
Author :
 Dr.surveen Ghuman
 Thanks to all those who would carry this
torch further.