Pathogenesis (etiology?) Hypersecretion of adrenal androgens? Hypersecretion of ovarian androgens? A genetic disorder with an autosomal dominant mode of inheritance? A multifactorial genetic disorder? Insulin resisrance 50% decreased sensitivity to insulin in peripheral tissues muscle and adipose tissue (but not in hepatic tissue )

LH FSH follicular maturation Androgen excess Extra glandular aromatization Stim. Of stroma and theca Chronic anovulation Adipose tissue acyclic estrogen Adrenal androgen Cyclic estrogen Ovarian androgen

Obesity Insulin Free testosterone SHBG IGF-1 5-alfa reductase activity is stimulated IGF*** insulin like growth factor

Presentation (STEIN-LEVENTHAL SYNDROM) Amenorrhea,Oligomenorrhea Infertility Hirsutism Acne OBESITY !

Other Symptoms “Dirty Skin” or Acanthosis Nigricans : This condition causes light brown to black rough patches around the neck and under arms. Migraines : Severe headaches that cause light sensitivity, nausea and dizziness. Courtesy of

Androgen excess society 2006 All these factors : Hirsutism and/or hyperandrogenemia Oligoanovolution and/or polycystic ovaries Exclusion of androgen excess or related disorders

NIH consensus criteria 1990 [1] (all required) Rotterdam criteria 2003* [2] (two out of three required) AES definition 2008 [3] (all required) Menstrual irregularity due to oligo- or anovulation Oligo- or anovulation Clinical and/or biochemical signs of hyperandrogenism Clinical and/or biochemical signs of hyperandrogenism Ovarian dysfunction – oligo- anovulation and/or polycystic ovaries on ultrasound Exclusion of other disorders: NCCAH, androgen-secreting tumors Polycystic ovaries (by ultrasound) Exclusion of other androgen excess or ovulatory disorders

Increased LH secretion: ?? Ratio of LH/FSH 2-3

measurement of antimüllerian hormone (AMH) concentrations may be useful in the diagnosis/confirmation of PCOS, although data are inconclusive and its routine measurement is not currently recommended

Increased androgen levels in blood (testosterone, androstendione) Increased LH, exaggerated surge Increased fasting insulin Increased estradiol and estrone levels Decreased SHBG levels Slightly rise in DEHEA Increased prolactin

serum testosterone undergoes episodic changes. Partly it is because norms are standardized for early morning on days 4 through 10 of the menstrual cycle in regularly cycling women because normal testosterone levels fall 10 percent from 8:00 AM to 4:00 PM and rise transiently during midcycle

Imaging ultrasonographgy number of cysts in ≥12 cysts with diameter of 2-9mm.

Long term risks in PCOS Type 2 diabetes Dyslipidemia diminished HDL and increased LDL Endometrial cancer

Hypertension Cardiovascular disease Gestational diabetes mellitus Ovarian cancer Long term risks in PCOS

Treatment

Oral Contraceptives contain two major hormones for ovulation : estrogen and progestin. oral contraceptive pills (OCPs) interfere with the assessment of androgens. They suppress gonadotropins, elevate SHBG, and directly inhibit steroidogenic enzymes such as 3ß-hydroxysteroid dehydrogenase (3ß-HSD). They normalize androgens in PCOS cuts the risk of endometrial cancer 50%.

If the woman is not hirsute and does not desire pregnancy: periodic withdrawal menses,with medroxyprogesterone acetate 10 days per month

decreasing peripheral estrogen formation (by weight reduction)

If pregnancy is desired ovulation must be induced. Insulin-sensitizing drugs, such as metformin and the thiazolidinediones. Clomiphene, letrozole hMG, urofollitropin,gonadorelin

Laparoscopic electrocautery persistence of ovulation and normalization of serum androgens and SHBG over many years effect on insulin resistance and serum lipids is not assessed