Polycystic ovarian syndrome is one of the leading causes of infertility and menstrual disturbances. It is an ovarian expression of the “metabolic syndrome” usually associated with hyperandrogenism, obesity, insulin resistance, abnormal hair growth and acne. At least 50 % of PCOS patients are obese.
Pathophysiology
It is primarily an endocrine condition manifesting as high LH/FSH ratio, increased androgen production and high oestrone levels. The gonadotropin pattern of high LH and low FSH can be due to increased frequency of GnRh pulsatile secretion , which in turn is attributed to a reduction in hypothalamic opioid inhibition because of the chronic absence of progesterone.
This is associated with increased secretion of LH which is also correlated to the level of circulating oestrogen.The constant elevated level of estrone may have its effect on hypothalamus resulting in tonic level of LH and negative feedback on FSH.
Failure of ovulation is related to the arrest of follicular growth at midantral stage.Constant level of FSH stimulates follicular growth and their lifespan may extend several months in the form of multiple follicular cysts , 2 to 10mm in size. As the follicles undergo atresia , new follicles of the limited growth potential replace them.The tissue derived from follicular atresia is substantial and contributes to the stromal compartment of the ovary.This functioning stroma secretes significant amount of androstenedione and testosterone.
Due to elevated LH, androgen secretion increases and this leads to increase in the extraglandular production of oestrogens.
Newer developments have focussed on the role of genetics and insulin resistance. insulin resistance is present in obese as well as non obese with PCOS.
There is high responsiveness to insulin by ovary as opposed to the resistance of the whole body. Insulin acts on ovarian stromal cells and there is hyperandrogenemia.
Clinical features - Menstrual irregularities, Hirsutism, Obesity, Acne, Infertility
Diagnosis
Transabdominal or Transvaginal ultrasonography
There should be at least 10 follicles (2 to 8 mm in diameter) arranged peripherally around a dense core of ovarian stroma.
Recent studies say that there should be at least 12 or more follicles (2 to 9 mm in diameter) or increased ovarian volume (more than 10 cubic centimeter) which can be diagnosed with the help of 3D ultrasound. single polycystic ovary is sufficient to prove the diagnosis. A woman having polycystic ovaries in the absence of an ovulation disorder or hyperandrogenism ( asymptomatic pcos ) may develop the syndrome if she gains weight.
Investigations with obesity Serum FSH ,LH Prolactin Androstenedione Total testosterone DHEAs BMI is very important.(weight in kg divided by height in m2)Obesity is considered when BMI is more than 30 kg /m2
Management
It is symptom oriented. Adolescents usually come with the history of amenorrhoea, acne, hirsutism, oligomenorrhoea or obesity. Weight reduction improves menstrual irregularities, reduces hirsutism and acne.lifestyle modification and dietary modification is required.
Induction of ovulation with clomiphene citrate 50 to 150 mg for 5 subsequent days from 2nd or 5th day of the cycle.
Metformin (demethyl biguanide) is an oral hypoglycemic agent widely used in the management of type 2 diabetes. It reduces the production of hepatic glucose and increases sensitivity of the peripheral tissues to insulin by increasing insulin receptors. It is given to all women ( obese / non obese ) with anovulatory infertility due to pcos ,however the risk of hypoglycemia with metformin in pcos is low. Metformin administration in obese PCOS women significantly improves insulin levels,reduces LH and testosterone levels regardless of any change in the body weight. Short term use of metformin with clomiphene improves ovulation rate.renal and hepatic functions must be checked. Metformin improves menstrual cyclicity and fertility within 6 months in 99%. It is given either 500 mg twice daily or 1 gm daily, can be given up to 1500mg / day. Low dose oral contraceptives and progesterones are also given for menstrual irregularities. If there is endometrial hyperplasia then withdrawal bleeding must be induced with the help of progesterones. EB should be done to exclude malignancy. Infertility associated with hyperandrogenism and hirsutism
Synthetic progestins like cyproterone acetate which is antigonadotropic and antiandrogenic+ethinyl oestradiol which controls androgens by inhibiting gonadotropin secretin is given. Krimson 35, Ginette are some of the drugs having these two combinations. These tablets come in calendar pack. One tablet daily for 21 days is given ,one week is kept free for withdrawal bleeding. LFT is done after 6 months of the treatment. Spironolactone Which is weak diuretic and antiandrogenic can also be given. DROSPIRENONE which is a derivative of spironolactone can also be given.Yasmin is the drug available containing drospirenone/ ethinyl oestradiol.
For Hirsutism Laser, Waxing, Chemical depilation can be done.
Surgical treatment:
for many years bilateral ovarian wedge resection was believed to be the only effective treatment of pcod or ”stein leventhal syndrome ”Ovulation rate was 60 % but pregnancy rate was as low as 30 to 40 % due to pelvic adhesions.In 1984 laparoscopic electrocautery was started.ovulation rate was 86 % and pregnancy rate 69 %. Ovarian drilling is done by making 4 to 10 holes 2 to 5 mm in diameter. Adhesion formation is still a risk. With laser ovulation rate is 68 % and pregnancy rate is 38 %.
Conclusion
PCOD is the commonest endocrine disorder in women. It’s management is symptom oriented. Weight loss OCPs, Dianette, Clomiphene citrate, Metformin ,Spironolactone, Flutamide are the line of treatment.Last two are not routinely used due to the side effects.
flutamide is used for the treatment of prostatic cancers but having lot of GI side effects usually not given.
Insulin sensitizers like metformin is very promising drug in the treatment of pcod.
If there is rapid onset hirsutism ,amenorrhoea persisting for more than 6 months in spite of the treatment or marked endometrial hyperplasia and refractory symptoms then refer the woman to a reproductive endocrinologist.