Women's Corner
Women's Corner
- The most common cause of this is android obesity, however it could be found in anovulatory non-obese women but to a lesser degree.
- Mechanism of insulin resistance and hyperinsulinemia : 2 separate mechanisms
a. Mutation : of the insulin receptor gene leading to decreased receptors in target tissue.
b. Obesity :
· Peripheral target tissue resistance to insulin : Fat of android obesity is more sensitive to catecholamines and less sensitive to insulin and thus more metabolically active resulting in a higher free fatty acid concentration which leads to hyperglycemia .
· Inhibition of hepatic clearance of insulin : due to androgens plus free fatty acids
- Which comes first hyperandrogenism or hyperinsulinemia :
It seems that negative effects of PCO and obesity on the action of insulin are synergisitc .
Evidences supports that hyperinsulinemia is the cause of hyperandrogenism :
· In vitro insulin stimulates thecal cells androgens production
· In women with PCO adminstration of insulin increases the circulating androgen levels
· In obeses women with PCO , adminstration of GnRH to normalize androgens does not change insulin level or insulin resistance
· In obese women with PCO , 20% have glucose intolerance or frank diabetes mellitus , whereas ovulatory hyperandrogenic women have normal insulin level and glucose tolerance .
· Weight loss decreases both androgens and insulin
- How does hyperinsnulinsim produce hyperandrogenism :
1. Activation of IGF-1 receptors : When the insulin receptors are blocked or defecient in number , insulin binds to the receptors of IGF-1 which is structurally similar to the insulin receptors . This binding in the thecal cells leads to augumentation of the thecal androgen response to LH which leads to increased thecal androgen production .
2. Decreased SHBG : Insulin inhibits its hepatic synthesis
3. Decreased IGFBP-1 : Insulin inhibits its hepatic synthesis .
- Syndromes associated with insulin resistance :
1. Hair-AN syndrome : Acanthosis nigricans , hyperandrogenism and insulin resistance
Acnthosis nigricans : A gray-brown velvety discoloration of the skin in the neck, axilla or groin . Histologically there is hyperkeratosis and papillomatosis . It is considered as a marker of insulin resistance and hyperandrogenism , however it could be found in normal women .
2. Leprechaunism : insulin resistance due receptor mutation, acanthosis nigricans and hyperandrogenism
3. Pseudoacromegaly
4. Anti-insulin receptor anibody
Pathological characteristics of the ovaries in PCO :
1. The surface is doubled , so the average volume increases 2.8 times
2. The same number of the primordial follicles is present but the number of the atretic follicles is doubled
3. The thickness of the tunica albuginia is increased by 50%
4. 5-fold increase in the subcortical stroma
5. There is 4-times more ovarian hilar cell hyperplasia
6. Variants : Hyperthecosis (sclerocystic disease)
- Diffuse hyperplasia and luteinisation of the ovarian stromal cells (theca cells) . Androgens production is more than with PCO , response to ovulation induction is usually poor and LH/FSH ratio is typically 1 .
- Pathogenesis : Higher androgens production which blocks the estrogen action on the hypothalamic pituitary level thus it is associated with lower LH levels and little or no follicles in the ovary and has a bad prognosis .
PCO-like syndromes :
1. Cushing syndrome
2. Adult-onset CAH
3. Hypothyroidism
4. Hyperprolactinemia
5. Androgen-producing ovarian or adrenal tumors .
dr. Hisham Al-Inany Lecturer in Obstetrics and Gynecology Department, Cairo University, Egypt Dr. Amr Hussein Lecturer in Obstetrics and Gynecology Department, Cairo University, Egypt