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Definition :

PCOD is a heterogenous, multisystem endocrinopathy in women of reproductive age with the ovarian expression of various metabolic disturbances. And with a wide spectrum of clinical features such as obesity, menstrual abnormalities and also hyperandrogenism. This disease was described by Stein and Leventhal and named as Stein – Leventhal syndrome. To diagnose PCOS, adrenal and androgen – producing ovarian tumors should be excluded.

Incidence :

Lately, the incidence of PCOS is increasing these years. This is because of lifestyle modification and stress amongst adolescents, developing soon after puberty. Amongst, infertile women, about 15 to 20 per cent of infertility cases are due to anovulation caused by PCOS. Some of the women who develop cardiovascular disease, hypertension and endometrial cancer and type 2 diabetes later in life appear to have suffered from PCOS in earlier years. Overweight and obesity are commonly present in such girls/ women.

Etiology and pathogenesis :

The exact cause of PCOS is unknown. Several theories have been postulated in the genesis of PCOS. Some of the well-known factors that influence the onset of PCOS are lifestyle changes, sedentary life, diet and stress. Initially, the ovaries were thought to be the primary site which sets the series of changes in the endocrine pattern resulting in PCOS. Genetic, familial and environmental factors are also etiological factors in the development of PCOS. The environmental factors may function in utero or early adolescent life, manifesting clinically a few years later as PCOS. CYP21 gene mutation occurs in this condition. Familial occurrence through the sex-linked mode of inheritance is also an etiological factor.

Another view held for the development of PCOS is an enhanced serine phosphorylation unification activity in the ovary and a reduced insulin receptor activity peripherally ( insulin resistance ). Obesity is related to PCOS. At least 50 to 70 per cent of patients with PCOS tend to be obese or overweight. The adipose tissue (fat) is an endocrine and immunomodulatory organ; it secretes leptin, adiponectin and cytokines which interfere with the insulin signaling pathways in the liver and muscles resulting in insulin resistance, and hyper insulinemia. Increased birth weight in obese and PCOS mothers can also cause PCOS in their adolescent daughters.

Raised LH secretion in response to increased insulin levels can cause infertility or miscarriage through improper oocyte maturation. Obesity is the condition when the body mass index is >30kg/m2and waist line >88cm; waist/hip ratio >0.85. Endogenous beta-endorphin also stimulates insulin release and may contribute to insulin resistance. Hyperandrogenism and resulting anovulation were initially thought to arise primarily in the ovaries. It has now been proved that insulin resistance with hyperinsulinemia initiates PCOS in 50 to 70% cases, though hypothalamic-pituitary-ovarian axis, adrenal glands also play a role in the genesis of PCOS to some extent.

Ovarian steroidogenesis in PCOS :

Insulin induces LH to cause theca-cell hyperplasia and secrete androgens, testosterone, and epi-androstenedione which are converted to oestrogen in the granulosa cells. The conversion of Epi-androstenedione to oesterone takes place in the peripheral fat. This leads to rise in the oestrogen and inhibin levels. These in turn cause high LH surge. Hyperandrogenism lowers the level of hepatic sex hormone-binding globulin, as a result levels of free testosterone in serum rises leading to hirsutism. Androgen also suppress the growth of the dominant follicle and prevents apoptosis of smaller follicles which are normally disappears in the late follicular phase.

PCOS may set in early adolescent life, but clinically manifest in the reproductive age. Later in life, there is an increase in risk of developing diabetes, hypertension, hyperlipidemia and cardiovascular disease later in life. This cluster off diseases is called the ‘X syndrome’ or ‘metabolic syndrome’.

Endocrinological changes in PCOS :

Osterone level increases; LH level raises to 10 IU/mL ; FSH level remains normal but FSH/LH ratio falls ; SHBG levels drop due to hyperandrogenism; Testosterone and Epi – androstenedione levels raises; Fasting blood glucose/fasting insulin ratio <4.5 suggests insulin resistance; Triglyceride level >150mg/dL- hyperlipidemia; High Density Lipoproteins (HDL) levels <50mg/dL,; Testosterone >2ng/mL, free T>2.2 pg /mL; Normal androstenedione; Raised Dehydroepiandrosterone Acetate Sulfate (DHEA – S) level; Prolactin is mildly raised in 15% of cases; Fasting insulin levels are raised(>10mIU/L in 50 -70% cases of PCOS); Thyroid function tests may be abnormal (Hypothyroidism); Urinary cortisol < 50mcg/24 hours.

Pathology :

Both ovaries enlarged. The ovaries show a thick white capsule of Tunica albuginea. The ovarian surface is slightly lobulated but the peritoneal surface remains free without any adhesions. Multiple cysts are present over the ovary giving it a ‘necklace appearance’ on the ultrasound. These are nothing but persistent atretic follicles. Theca-cell hyperplasia and stromal hyperplasia accounts for the increase in size of the ovary which amounts to more than 10 cm3 in volume.

Clinical features :

The clinical features of PCOS include Oligomenorrhoea, amenorrhea, Infertility, Hirsutism, Acanthosis nigricans due to insulin resistance; thick pigmented skin over the nape of the neck, inner thigh and axilla and also central obesity. In the reproductive years, there maybe longer periods of infertility and this occurs due to anovulatory cycles. If a women with PCOS conceives she may develop carbohydrate intolerance, diabetes, and hypertension. Pregnancy loss occurs in 20 -30% cases due to abortions.

Hyperandrogenism occurs in the form of acne and also hirsutism. Facial hair appears over the upper lips, chin, breasts and also thighs. Baldness is sometimes present but virilism does not occur. History of lifestyle, diet and smoking and also exogenous hormone administration should also be enquired. And also to elicit a history of diabetes and also hypertension in the family members.

Examination of a Girl with PCOS :

Look for Obesity, especially waistline. Waist-to-hip ratio > 0.85 is abnormal; 50% of women are obese, Body Mass Index between 25 and 3 – overweight; and above 30 – obesity; Thyroid enlargement; Hirsutism and also acne; Hyperinsulinemia which may manifest as Acanthosis nigricans over the nape of the neck, axilla and below the breasts; 75% of obese PCOS women have hyperinsulinemia; blood pressure in Obese women. Pelvic findings are usually normal and it is not easy to palpate the enlarged ovaries. Avoid per vaginal examination in unmarried girls.

Diagnostic criteria for making a diagnosis of PCOS :

For the diagnosis of PCOS, the Rotterdam criteria are generally followed. It states that at least two of three criteria should be present. These criteria are as follows : Oligomenorrhoea, amenorrhea, anovulation, Hyperandrogenism, Hirsutism, Acne and also ultrasound features of PCO.

Differential diagnosis :

The differential diagnosis of PCOS is Congenital or Adult adrenal hyperplasia, Cushing disease and also Ovarian male hormone-producing tumors.

Investigations :

Ultrasound is very useful for making a diagnosis of PCOS. It confirms the enlarged ovaries, their size and increased stroma. The ovarian volume will be more than 10mm3.USG shows 12 or more small follicles each 2 – 9mm in size placed peripherally in the subscapular region of the ovaries. It helps to rule out ovarian tumor. It can also show endometrial hyperplasia, if present.

In cases with suspicion of adrenal tumor /Adrenal hyperplasia, abdominal scan, estimation of DHEA, 17-OH hydroxyprogesterone level will help in the diagnosis of these conditions. To make the diagnosis of PCOS, ultrasound should preferably be performed in the early follicular phase. An increased blood flow is sometimes in the early follicular phase. An increased blood flow is sometimes revealed on Doppler ultrasound. Ultrasound is also used to watch the response to medication and to decide when to stop the drug therapy. Sometimes, only one ovary may show features of PCOS. These ovarian changes cannot be relied upon if a women is on combined oral pills, as these pills change the ovarian morphology. To do thyroid function tests in an obese women. In most cases diagnosis can be confirmed on the basis of history and ultrasound. Laparoscopy reveals enlarged bilateral ovarian cysts.

Treatment :

Treatment aims to take care of menstrual disorders, treat Hirsutism, to treat infertility and prevent long-term effects in the form of X-Syndrome in later life. The treatment modality is different and it is based according to the individual requirement of the women.

Weight loss of more than 5 – 10 % over previous weight alone is beneficial in mild PCOS; it restores the hormonal milieu considerably. weight loss increases the secretion of the SHBG, reduces insulin level and testosterone level. Lifestyle changes such as stopping cigarette smoking. This helps to lower the E2 level and raises DHEA and androgen levels.

Hormonal treatment :

Hormones to regulate menstruation are as follows that is Oral combined pills, oral pills containing cyproterone acetate or drospirenone, Spironolactone and OCs in combination. oestrogen in the oral pills suppresses the androgens and adrenal hormones (DHEA). it raises the secretion of SHBG in the liver, which binds with testosterone, thus reducing free testosterone. It also suppresses LH. It is given as low-dose. Fourth generation of combined pills which containing 30 mcg E2 and 3 mg drospirenone (progestogen with anti=-androgenic action) are best for PCOS. It helps to reduce acne and further development of hair. It also prevents water retention and reduces weight; it maintains lipid profile. Progestogen may be required to induce menstruation in an amenorrhoeic woman prior to initiation of a hormonal therapy. Oral contraceptive pills containing cyproterone is drug of choice for the women having hirsutism as the main symptom. Eflornithine cream topically prevents hair growth.

Acne can be managed by Clindamycin lotion 1% or Erythromycin gel 2%. And for severe acne isotretinoin is used. Since it is a teratogenic drug, pregnancy must be avoided while taking the drug. The drugs take 3 – 6 months before improvement in hirsutism is noted.

Treatment for Infertility :

Dexamethasone can be given to reduce androgen secretion, and is used in some infertile women if the level of DHEA-S is raised above 5ng/mL . For improving infertility Clomiphene citrate along with dexamethasone is given. In case of Clomiphene resistant, tamoxifen citrate or Letrozole can be given. A woman with insulin resistance requires metformin in addition to the above medications.

Role of Surgery :

Surgery stays as the mainstay of treatment in case of PCOD if the medical therapy fails, Hyperstimulation of Ovaries occurs during ovulation induction, Infertile women and also Previous pregnancy losses. It includes drilling or puncture of not more than four cysts in each ovary either by laser or by unipolar electrocautery. Surgery restores endocrine milieu and improves fertility for a period of 6 to 12 months.

Tubal testing with Chromotubation can be doneInvolves anesthesia and laparoscopy
Other causes of infertility can be found Adhesions may form around ovaries postoperatively
One time treatmentPremature ovarian failure
No need of intense or long duration monitoringDecrease in ovarian reserve
Cost effective
No need of Hyperstimulation for induction of ovulation

IVF for managing Infertility due to PCOS :

If a women fails to ovulate after common regimen used for ovulation induction, then IVF is preferred.

Prevention :

Obesity in adolescents to be corrected and avoided; recommend life style changes; treat the long term ailments like Diabetes, Hypertension, Cardiovascular changes, endometrial cancer and also Hyperlipidemia.

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