Ovarian amenorrhea
1- Premature ovarian Failure;
* Aetiology: Functional defect of ovary, may be
– Constitutional; in some families.
– Chromosomal: Missed or extra chromosomes, e.g.
– Female mosaic turner 45 XO, 46 XX
– Trisomy 18 and 13.
– Autoimmune diseases.
* Diagnosis: * Menopausal symptoms appear earlier (before 40 years).
* FSH >40 mlU/ml, (indicating ovarian failure).
* Treatment: Menopausal symptoms controlled by HRT (Estrogen).
2- Resistant ovary syndrome; (Savag syndrome);
* The ovaries don’t respond to GnRH; no receptors.
* Diagnosis: – Amenorrhea and infertility; follicular function impaired.
– FSH > 40 mlU/ml, (indicating ovarian failure).
– Ovarian biopsy: primordial follicles are present, (not preferred).
* Treatment: GnRH receptors can be increased by large doses of estrogen.
3- Turner syndrome (gonadal dysgenesis):
– Chromosomal pattern 45 XO.
– In some cases, mosaics is present
– Mosaic turner i.e. 45 XO/46 XX or 45 XO/46 XY.
* Diagnosis:
– 1ry amenorrhea.
– Ovarian biopsy; fibrous tissue (streak gonads).
– The uterus and vagina are underdeveloped.
– General examination; revealing turner stigmata.
a- Short stature.
b- Webbing of the neck.
c- Widely spaced nipples, & Coarctation of aorta,
d- Cubitus valgus.
e- Deformities of finger and toes.
* Investigations:
– Hypogonadotrophic (High FSH >40 mlU/ml).
– Hypogonadism, low estrogen.
– Buccal smear → absent Barr body (Cell contain only one X chromosome).
– Karyotyping → 45 XO.
– Laparoscopy with ovarian biopsy: streak gonads.
* Treatment:
– Estrogen therapy → Feminine appearance (2ry sex characters).
→ Prevents osteoporosis.
* Progesterone is added to avoid carcinogenic effect of excess
unopposed estrogen on endometrium.
* Treatment is delayed to avoid premature closure of epiphysis
and subsequently short stature.
4- Destructed ovary;
– By irradiation, surgical removal or destructed by inflammatory reaction e.g. TB.
5- Polycystic Ovarian disease (PCO);
♦ Synonyms; Stein-Leventhal syndrome and (chronic anovulation):
* Definition:
– A syndrome of ovarian dysfunction along with the cardinal features of hyper
androgen ism and polycystic ovarian morphology.
– Its clinical manifestations may include – Menstrual irregularities,
– Signs of excess androgen, and
– Obesity.
* Etiology: Unknown may be:
1- Hereditary disease, with X-linked dominant inheritance.
2- Endocrine disturbance:
– Ovarian disorder (aromataze deficiency) resulting in
accumulation of produced androgen without conversion.
– Adrenal disorder with excess androgen production.
– Hypothalamic and/or pituitary (FSH/LH abnormalities).
3- Obesity with insulin resistance; excess insulin can stimulate ovarian
peptide responsible for enzymatic activity (LH like action).
* Pathophysiology:
* The enzyme system (aromatase enzyme) fails to convert androstenedione to estradiol in the ovary.
* Excess androstenedione has a local effect on ovary leads to:
a- Ovarian capsule → Thickened.
b- Follicular maturation → arrested so anovulation results.
c- Ovary contains multiple small cysts (8-12 mm).
* Excess androstenedione has another systemic effect i.e. hirsutism.
* Peripheral conversion; Fat cells play important role on androstenedione conversion to estrone (El) which causes:
a- Amenorrhea; due to endometrial proliferation with risk
of endometrial hyperplasia and carcinoma.
b- Excess LH production; Alteration of amplitude and
frequency of pulsatile secretion of GnRH.
c- Excess LH stimulates the theca cells of the ovary to produce
more androstenedione setting a vicious circle.
d- Adrenal androgen secreted in excess due to blockage of
enzyme system in suprarenal.
☺☺ Role of insulin:
– IGF1 (Insulin like Growth Factor 1) expressed in ovarian stroma and theca cells.
– Insulin binds to IGF1 stimulating androstenedione and testosterone production.
– Insulin and LH operate upon IGF1 in a synergistic manner.
☺☺ Role of Obesity:
* Obesity is associated with 3 alterations in normal ovulation.
– Increased estrone production by peripheral conversion of androgen in fat cells.
– Increased levels of free estrone and testosterone (decreased SHBG).
– Increased androgen production from ovarian stroma (effect of ↑ insulin).
* All the previous 3 are improved by weight reduction.
* Diagnosis:
a- Clinical picture:
– Obesity. – Amenorrhea. – Hirsutism. – Infertility.
b- Investigations:
– Ultrasonography: – Ovaries; multiple small subcapsular cysts,
– Uterus; thick endometrium.
– Hormonal assay: – LH/FSH ratio: more than 3: 1.
– Excess androgens and estrone (E1).
– Laparoscopy: – Enlarged ovaries (2-3X ordinary size).
– Capsule of the ovary is smooth, whitish.
– Endometrial biopsy: Absent secretory activity.
* Treatment:
1-Reduction of weight.
– Metformin 500 mg bid, in some cases, can improve the condition lonely.
2- If pregnancy desired; induction of ovulation:
– Ovulation induction protocols;
* GnRH analogues (suppress LH).
* Clomiphene citrate.
* Purified FSH.
– Dexamethazone added to treatment protocols to decrease adrenal androgens.
3- If pregnancy not desired;
– Cyclic progesterone Protect endometrium from carcinogenic effect
of excess unopposed estrogen.
4- Treatment of hirsutism if present.
– Androgen antagonist
– Local management of hair e.g. epilation or laser ablation.
☺☺ Resistant cases for induction of ovulation.
– Ovarian drilling by laparoscopy: 5- 8 holes are done by electrocautery.
– Bilateral wedge resection (surgically) of the ovary.
* It is very rarely done as it induces adhesions.
* The action is thought to be through decreasing androgen secreting pole.
6- Virilizing ovarian Tumors;
* Ovarian tumors that secret androgen e.g. androblastoma, lipoid cell
tumor, hilar cell tumor and sometimes gynandroblastoma.
* Diagnosis: – Defeminization; regression of feminine criteria, or
– Virilization; development of masculine criteria.
– Assessment of ovarian mass (clinical and U/S).
* Treatment: Surgical removal.
☺☺ Other ovarian conditions:
7- Continuous estrogen production:
– Metropathia hemorrhagica: short period of amenorrhea followed
by excessive prolonged painless bleeding.
8- Continuous estrogen & progesterone production;
– Halban’s disease; Short period of amenorrhea, corpus luteum cyst.
9- Ovarian hypofunction: Under development of ovary may lead to
oligohypomenorrhea or amenorrhea.
Ovarian amenorrhea videos:
Ovarian amenorrhea – Polycystic Ovary Syndrome | PCOS | Nucleus Health video
Ovarian amenorrhea – Polycystic Ovary Syndrome (PCOS) for USMLE video
This video will cover ovarian amenorrhea – Polycystic Ovary Syndrome (PCOS) for USMLE. We will be going over pathophysiology, clinical signs and symptoms and management.
