Various factors that contribute to this rise are calorie dense nutrition, sedentary life style, and propagation of the gene pool due to successful treatment of infertility in this population.

The diagnostic criterion of PCOS are polycystic ovarian morphology (PCOM) on ultrasound, increased ovarian volume, and raised levels of anti-Müllerian hormone (AMH). The cutoff values are not clearly defined as they may show variations among different ethnic subgroups. Insulin resistance and hyperandrogenemia coexist in many.

The phenotypic presentation may be diverse and four different types have been recognized ().

The inheritance pattern may be complex with involvement of multiple genes that are modified by phenotypical and environmental factors. These genes often seem to come from paternal lineage and cause PCOS in the female and early onset of male pattern baldness in the male offspring. Recent profiling of deoxyribonucleic acid (DNA) methylome in PCOS patients suggests that it could be an epigenetic disorder. Others have postulated that insulin resistance could also be an autoimmune phenomenon.

FM12Sedentary lifestyle with lack of exercise is the most important contributor to the development and perpetuation of insulin resistance which induces weight gain, further enhancing insulin resistance, a vicious cycle that is very hard to break. Intraovarian hormonal mileu responds to insulin resistance by increasing levels of intraovarian androgens that leads to arrest of primordial follicles in the antral phase, rise in granulosa cell population and AMH levels. Rise in intraovarian estrogen and androgen levels exert a negative feedback on hypothalamic pituitary axis, blunting the cyclical rise in follicle-stimulating hormone and luteinizing hormone (LH) levels required to induce ovulation. Thus, the body is in a state of hyperestrogenemia and tonic high LH levels but deficient in progesterone, which is responsible for oligomenorrhea and oligoovulation.

Insulin resistance also increases truncal adiposity. Fat being an endocrine organ promotes peripheral conversion of estrogens to androgens, in the presence of the enzyme aromatase. Circulating androgens activate the pilosebaceous unit to cause seborrheic dermatitis, hair fall, acne, hirsutism, and acanthosis nigricans. Weight gain, oligomenorrhea, hisrsutism, and acne result in a negative body image in adolescent girls, causing social isolation, which promotes emotional eating that further propagates this vicious cycle of obesity. The insidious onset of subclinical depression in many teenagers contributes to lack of exercise and promotes insulin resistance, mood swings, insomnia, and chronic fatigue. The incidence of teenage suicide is rising and we as a society need to wake up and curb this rising incidence.

Preventive action needs to be taken at the adolescent stage by promoting daily exercise for at least 30 minutes. Exercise, especially outdoor, increases endorphin levels, lowers insulin resistance, and induces sustainable weight loss by increasing muscle mass. Exercise needs to be fun like dancing, swimming, sports like squash, badminton, tennis, golf, etc. Group activities are better as they increase compliance and break the cycle of social isolation, thereby further elevating mood. To start with it may be low impact exercise, which can then be escalated to high impact exercise. Nonexercise activity also needs to be promoted by keeping a count of number of hours spent sitting or reclining in a day.

Passive muscle stimulation is not a substitute. It does not lead to sustained toning of the muscle and also does not elevate mood. It may also result in harm in the hands of the untrained.

Calorie restriction on the other hand is often difficult to follow, and, after a short period of compliance, results is rebound indulgence as well as weight gain. Hence it should be instituted sympathetically, allowing for periods of gratification to break the monotony and elevate mood. Use of high fiber fillers to induce satiety and substitution of sweeteners in desserts along with a high protein low carbohydrate diet coupled with periodic fasting is the most successful combination for weight loss.

Bariatric surgery is indicated if the body mass index (BMI) is over 35 in any age group to prevent long-term morbidity and improve body image issues.

FM13Cosmetic concerns need to be seriously addressed with both temporary as well as permanent methods of hair removal and suppression of acne.

Treatment of oligomenorrhea/ovulation is by achieving an ideal BMI. Metformin therapy is ideal as it reduces insulin resistance and promotes weight loss. Use of other insulin sensitizers like myo-/D-chiro-inositol, as well as N-acetyl cysteine may be considered as adjuvants to metformin or when metformin is not tolerated due to its gastro intestinal side effects or lactic acidosis. As this is achieved, insulin resistance decreases and the vicious cycle gets reversed. Use of aromatase inhibitors is ideal as this will reduce the peripheral as well as intraovarian rise of androgens. This will not only correct oligoovulation but will also cause reduction in hyperandrogenemia.

Where ovulation induction is not a priority, balancing the high estrogen level with periodic addition of progestogens to induce withdrawal bleeding 3–6 times a year is more acceptable than the use of a cyclic oral contraceptive pill (OCP). It mitigates serious sequelae of hyperestrogenemia like endometrial hyperplasia/carcinoma, uterine leiomyomas, and breast cancer. However, the fourth generation OCP that contain anti-androgens, like cyproterone acetate/drosperinone, are beneficial in reducing facial hair as well as clearing acne. Use of anti-androgens like spironolactone and finasteride may be required in select few with high androgen levels. Women with late onset congenital adrenal hyperplasia often present with PCOS but have high levels of 17-hydroxyprogesterone, androstenedione, and/or DHEA-S which may require steroid therapy to suppress the overactive adrenal cortex prior to ovulation induction and during pregnancy.

The endocrinal derangements also result in hypertriglyceridemia, and the ratio of triglyceride to high-density lipoprotein rises. This promotes coronary artery disease (CAD) in the long run. Obesity predisposes to hypertension with its resulting sequelae of CAD, stroke, and chronic kidney disease. Obesity is also intimately linked with obstructive sleep apnea and resultant chronic fatigue syndrome. Early onset of osteoarthritis and spinal instability further reduces mobility and worsens the quality of life. Hence, a simple issue of increased insulin resistance proliferates to a mutisystem disorder with implications not just for reproductive health but also metabolic, cardiovascular, neurological, and mental health.

Reproductive gratification is achieved with induction of ovulation in the majority of cases with, either clomiphene citrate, aromatase inhibitors, and/or gonadotropins. In a small minority, ovulation induction is troublesome requiring the use of gonadotropins in combination with gonadotropin releasing hormone antagonist to blunt the premature LH surge. Ovarian hyperstimulation syndrome (OHSS) is a dreaded complication, and requires intense vigilance of a stimulated cycle by both ultrasound and hormonal monitoring. Cycle cancellation, conversion to in vitro fertilization, and freezing all embryos are sure shot methods of avoiding both early and late OHSS. However, in milder cases, substitution of human chorionic gonadotropin (hCG) with an agonist/dual trigger, avoidance of hCG forFM14 luteal support, and use of cabergoline to block the rise in vasculoendothelial growth factor are recommended. Ultrasound monitoring for ovarian size and appearance of free fluid in pelvis and abdomen will alert the clinician to onset of late OHSS, which may sometimes require hospitalization and multidisciplinary intensive care for a few weeks. It is in these patients with difficult ovulation induction that cautious laparoscopic ovarian diathermy is advisable to reduce morbidity and reduce the incidence off higher order multiple births. Ovulation induction has to be coupled with reduction in insulin resistance and hyperandrogenemia in order to prevent early pregnancy loss. There is some evidence of increased activity of plasminogen activator inhibitor-1, which may contribute to a hyper coagulable state.

Pregnancy is high risk in this subgroup due to concurrent obesity and insulin resistance. There is a higher incidence of pregnancy induced hypertension, preeclampsia, preterm labor, fetal growth restriction, difficulty in per abdominal fetal monitoring, and gestational diabetes with fetal macrosomia, polyhydramnios, and cord accidents. Screening for gestational diabetes is mandatory along with close monitoring of blood pressure with a wide cuff. Screening tests for preeclampsia like low levels of Placenta Associated Plasma Protein A (PAPP A), soluble fms-like tyrosine kinase/placental growth factor may also be considered. Promoting low impact exercise on a daily basis during pregnancy along with calorie restriction will go a long way to improve fetal well being as well as ingrain lifestyle modifications that need to be followed lifelong.

Abnormal uterine bleeding, endometrial hyperplasia, and endometrial cancer are the consequences of long-term hyperestrogenemia. Screening for these disorders and treating them with progesterones, levonorgestrel intrauterine system, local endometrial ablative techniques, and finally hysterectomy may be required. Benign breast lesions and breast carcinoma are also estrogen dependent and women with PCOS need to be educated in self breast examination, and motivated for screening mammographies between the ages of 45 and 60 years. Women with a family history of breast cancer will benefit with BRCA1 and BRCA2 screening and subsequent close follow-up in the positive cohort.

Future research is focusing on modern genetic approaches, such as genome-wide association studies, Mendelian randomization, and next-generation sequencing. It promises to identify the pathways that are primarily disrupted in PCOS. In addition, phenome wide association studies may be required to link the varied phenotypes with their genotypes.