Premature Ovarian Failure in brief

1. Premature Ovarian
Failure
ANISH DHAKAL
(ARYAN)

2. Contents
Premature ovarian failure
◦ Introduction
◦ Incidence
◦ Etiology
◦ Pathophysiology
◦ Clinical features
◦ Investigations
◦ Diagnostic criteria
◦ Complications
◦ Management

3. Introduction
Secondary amennorhea due to ovarian failure occurring spontaneously
before 40 years of age
The term "failure" means that ovarian function is not normal, but does
not necessarily imply total cessation of ovarian function.
Patients with primary ovarian insufficiency may intermittently produce
estrogen, ovulate & 5-10% of them conceive, have normal pregnancy &
delivery

4. less than 40 years old has had amenorrhea for
4 months or more, with two serum FSH levels
(obtained at least 1 month apart) in the
menopausal range--NEJM
Before puberty - 0 to 4.0 mIU/mL (0 to 4.0 IU/L)
During puberty - 0.3 to 10.0 mIU/mL (0.3 to 10.0 IU/L)
Women who are still menstruating - 4.7 to 21.5 mIU/mL (4.5
to 21.5 IU/L)
After menopause - 25.8 to 134.8 mIU/mL (25.8 to 134.8
IU/L)
Source: https://medlineplus.gov/ency/article/003710.htm

5. Incidence
The age specific incidence of spontaneous primary ovarian
insufficiency is approximately
Before 30: 1 in 1000
At 35: 1 in 250
Just before 40: 1%

6. Etiology
1. Genetic
◦ Two intact X chromosomes are necessary for maintenances of
follicles
◦ Structural abnormalities to the X chromosomes lead to follicles loss
◦ Chromosomal abnormalities include;
Turner syndrome
Fragile X syndrome
Autosomal dominant

7. Etiology
2. Autoimmune
◦ Associated with women who have polyglandular failure
including thyroiditis, hypoparathyroidism, hypoadrenalism
◦ Ovarian biopsy  infiltration of the follicles with
plasma cells and lymphocytes
◦ Presence of anti-ovarian antibodies
◦ Presence of anti- adrenal antibodies

8. Etiology
3. Tuberculosis of the genital tract involving
the ovaries
4. Smoking
5. Radiation and chemotherapy
Reversible effect  ovary may resume
ovulation and menstruation after about a year
of amenorrhoea
Alkylating agents
6. Prolonged GnRH therapy

9. Etiology
7. Metabolic
◦ Deficiencies of galactose 1
phosphate uridyltransferase
(defect in Leloir pathway)
high level of galactose toxic
to oocyte
8. Resistant ovary
◦ Follicles fail to respond to
gonadotropin stimulation

10. Etiology
9. Induction of multiple ovulation (infertility) 
exhaustion of follicles  premature menopause
10. Surgical
◦ Hysterectomy  kinking and blockage of ovarian
vessels premature ovarian failure (15-50%)

11. Source: Gyanecology by ten teachers, B.Helen et al.

12. Pathophysiology
Follicle dysfunction
◦ Follicle remain in the ovary
 Pathological process prevents its normal function
◦ e.g. FSH receptor mutation
Follicle depletion
◦ No primordial follicles in the ovary
 Failure of establishment of an adequate initial pool of primordial follicles in
uterine life
 Accelerated expenditure of follicles
 Autoimmune or toxic destruction of follicles

13. Clinical Features
◦ Amenorrhea
◦ Hot flushes
◦ Sweating
◦ Insomnia
◦ Headache
◦ Psychological
◦ Cancer phobia
◦ Pseudocyesis
◦ Irritability
◦ Depression
◦ Lack of concentration

14. Investigations
FSH level: 40 mIU/ml or more
E2 level: 20 pg/ml or less
Thyroid function, and thyroid antibodies,
calcium level, chromosomal study
Prolactin level
Blood sugar
Pregnancy test

15. Investigations
X-ray pituitary fossa for tumor
BMD study-not always necessary
Ovarian biopsy
Ultrasound

16. Diagnostic criteria:
Women younger than 40 years who have had
 3 months of amenorrhea, oligomenorrhea or
dysfunctional uterine bleeding
in association with FSH levels in the menopausal
range

17. Complications
Risk of:
◦osteoporosis and
◦ cardiovascular disease

18. Management
1. Treat the cause first
2. Ovulation induction (by
administration of sequential estrogen
& progesterone or by use of GnRH
agonist followed by administration of
gonadotropins)
3. oocyte donation in IVF to cause
pregnancy

19. 4. Progesterone challenge test to assess endogenous
estrogen
5. Corticosteroid therapy and Plasmapheresis in
autoimmune disease

20. 6. In presence of Y chromosome, gonadectomy is to
be done to avoid malignancy.
7. HRT (Oestrogen implant with progestogen or
Mirena IUCD) in a women with hypo-oestrogenism
to prevent osteoporosis
-estrogen implant with progesterone or Mirena
IUCD offers long term HRT

21. References:
1. Howkins and Bourne, Shaw’s Textbook of
Gynecology, 16th edition
2. Up to date 21.6
3. Gynecology by Ten teacher, 20th Edition

22. Thank you