Polycystic Ovaries Syndrome 2024 PDF

Polycystic ovarian syndrome Dr.Khalida Hassan Muho Specialist OB\GYN Objectives Understand the difficulty in defining polycystic ovarian syndrome (PCOS) Be able to discuss the importance of lifestyle, environmental factors on the progress of PCOS Be able to describe the classical u...

Polycystic ovarian syndrome Dr.Khalida Hassan Muho Specialist OB\GYN Objectives Understand the difficulty in defining polycystic ovarian syndrome (PCOS) Be able to discuss the importance of lifestyle, environmental factors on the progress of PCOS Be able to describe the classical ultrasound appearance of polycystic ovaries Know the different types of drugs used in the management of PCOS, A 32-year-old woman visits the gynecologist's office complaining of vaginal bleeding, facial hair growth, and obesity. She states that she has noted the facial hair growth for many years and the irregular bleeding has been progressively getting worse during the past 6 months. She has no other significant personal or family history, and on pelvic examination she has slightly enlarged bilateral ovaries. Polycystic ovarian syndrome PCOS is a syndrome of ovarian dysfunction along with the cardinal features of hyperandrogenism and polycystic ovary morphology. Its clinical manifestations include menstrual irregularities, sign of androgen excess(e.g. hirsutism),obesity, elevated serum LH levels and insulin resistance. Polycystic ovarian syndrome (PCOS) is a common endocrine disorder, affecting women of reproductive age. Prevalence :it affects around 5-10% of women of reproductive age. The prevalence is also higher in certain ethnic groups, such as South Asians, who may also suffer from more severe symptoms. AETIOLOGY AND PATHOPHYSIOLOGY The aetiology of PCOS is largely unknown, but seems to involve a complex interaction between environmental (e.g. diet and exercise) and multiple genetic factors. The mode of inheritance appears akin to an autosomal dominant pattern. Several factors have been implicated in the pathogenesis of PCOS, including a dysfunction of ovarian function characterized by increased production of ovarian androgens. a dysfunction in hypothalamic function resulting in increased LH secretion which in turn stimulates androgen production by the theca cells.  and insulin resistance which is a characteristic of both obese and non- obese PCOS patients.  PCOS No ovulation Infrequent ovulation Ovulation Progesterone What causes PCOS? GENETICS LIFESTYLE Hormonal Changes ↑ Androgens ↑ Insulin OVARIES CARDIO- Hair Growth Anovulation VASCULAR Acne Irregular RISK Periods  PCOM PCOM (polycystic ovarian morphology)  PCOM PCOM (polycystic ovarian morphology) Clinical features: Oligomenorrhoea/amenorrhoea in up to 75% of patients, predominantly related to chronic anovulation. Hirsutism (due to increase level of androgen). Subfertility in up to 75per cent of women(anovulatory). Obesity: in at least 40 per cent of patients.  Recurrent miscarriage: in around 50-60 per cent of women. Acanthosis nigricans:(areas of increased velvety skin pigmentation occur in axillae and other flexures. May be asymptomatic. Key features include menstrual cycle disturbance, hyperandrogenism and obesity. Patches of dark skin on the back of the neck or other areas Diagnosis History: o ask patient about excess facial hair growth, acne ,Increase body weight, o previous menstrual history of the patient as if there is any irregularity, o history of any previous miscarriage, o family history of hirsutism and menstrual dysfunction.  Examination: general examination should be made including observation of the body build, weight and hair distribution(the degree of hirsutism, acne and androgenic alopecia should be assessed). Investigations: Include U/S, hormonal level and evaluation of metabolic status. 1. The Ultrasound appearance of the ovaries: presence of >12 follicles in each ovary measuring 2-9 mm and/or increased ovarian volume (>10 mL).Whilst these findings support a diagnosis of PCOS, they are not by themselves sufficient to identify the syndrome.  Polycystic ovaries are commonly detected by ultrasound or other forms of pelvic imaging, with estimates of the prevalence in the general population being in the order of 20-33%. 2. Serum endocrinology ↑ Fasting insulin (not routinely measured; insulin resistance or impaired glucose tolerance assessed by GTT) ↑ Androgens (testosterone and androstenedione)  ↑ Luteinizing hormone (LH), usually normal follicle stimulating hormone (FSH) Decrease Sex hormone binding globulin (SHBG), results in elevated ‘free androgen index’ ↑ Oestradiol, oestrone (neither measured routinely as very wide range of values) ↑ Prolactin. Diagnosis Patients must have two out of the three features below: Oligomenorrhoea/amenorrhoea. Clinical or biochemical hyperandrogenism. Polycystic ovaries on ultrasound.  Menstrual Irregularities PCOS PCOS PCOS Androgens Ultrasound PCOS Long-term sequelae Emerging evidence suggests that women with PCOs are at increased risk of developing diabetes and cardiovascular disease later in life. lifestyle advice (such as dietary modification and increasing exercise) is appropriate.  Possible late sequelae Diabetes mellitus Dyslipidaemia Hypertension, cardiovascular disease Endometrial carcinoma Breast cancer Management of the polycystic ovary syndrome The clinical management of a woman with PCOS should be focused on her individual problems. OBESITY Obesity worsens both symptomatology and the endocrine profile and so obese women (BMI >30 kg/m2) should therefore be encouraged to lose weight. Weight loss improves the endocrine profile, the likelihood of ovulation and a healthy pregnancy. Keep carbohydrate content down and to avoid fatty foods. Metformin has not been shown to be valuable to aiding weight reduction. A GTT should be performed if the BMI is >30 kg/m2. Some obese PCOS patients, however, will find it difficult to achieve adequate weight loss with diet and exercise alone in which case the use of weight-losing drugs may be indicated. There are two weight-losing drugs currently licensed in the United Kingdom, the centrally acting serotonin and norepinephrine uptake inhibitor, sibutramine, and the peripherally acting lipase inhibitor, orlistat. Both medications have been shown to be effective at producing a modest weight loss together with a well-balanced diet. Bariatric surgery The guidelines of the National Institute for Health and Clinical Excellence (NICE) state that, 'Surgery is recommended as a treatment option for people with morbid obesity (body mass index equal to or greater than 40 kg/m2) or with a body mass index (BMI) equal to or greater than 35 kg/m2 in the presence of significant co-morbid conditions that could be improved by weight loss'. Laparoscopic adjustable gastric banding (LAGB) is a technique particularly suitable for women with fertility problems, since the band tightness can be varied to accommodate the increased demands of pregnancy when it occurs. MENSTRUAL IRREGULARITY Amenorrhoeic women with PCOS are not oestrogen deficient and are not at risk of osteoporosis. Indeed they are oestrogen replete and at risk of endometrial hyperplasia.The easiest way to control the menstrual cycle is the use of a low-dose combined oral contraceptive preparation (COCP). This will result in an artificial cycle and regular shedding of the endometrium.  An alternative is a progestogen (such as medroxyprogesterone acetate [Provera] for 12 days every 1–3 months to induce a withdrawal bleed, or the continuous provision of progesterone into the uterine cavity by Mirena. It is important once again to encourage weight loss. INFERTILITY Improvement in lifestyle with a combination of exercise and diet to achieve weight reduction is important to improve the prospects of both spontaneous and drug induced ovulation. In addition, overweight women with PCOS are at increased risk of obstetrical complications, including gestational diabetes mellitus and preeclampsia.  Ovulation can be induced with 1. the antioestrogen clomifene citrate (50– 100 mg) taken from days 2–6 of a natural or artificially induced bleed. While clomifene is successful in inducing ovulation in over 80% of women, pregnancy only occurs in about 40%. Clomifene citrate should only be prescribed in a setting where ultrasound monitoring is available (and performed) to minimize the 10% risk of multiple pregnancy and to ensure that ovulation is taking place. A daily dose of more than 100 mg rarely confers any benefit and can cause thickening of the cervical mucus, which can impede passage of sperm through the cervix. Once an ovulatory dose has been reached, the cumulative conception rate continues to increase for up to 10–12 cycles. 2. Parenteral gonadotropin therapy: is the therapeutic options for patients with anovulatory infertility who are resistant to antioestrogens. Because the polycystic ovary is very sensitive to stimulation by exogenous hormones, it is very important to start with very low doses of gonadotropins and follicular development must be carefully monitored by ultrasound scans. 3.Laparoscopic ovarian diathermy: is free of the risks of multiple pregnancy and ovarian hyperstimulation and does not require intensive ultrasound monitoring. 4.wedge resection of the ovaries: this operation is no more used nowadays because it cause in extensive peri- ovarian and tubal adhesions Ovarian hyperstimulation syndrome (OHSS) Women with the polycystic ovary syndrome are also at increased risk of developing the ovarian hyperstimulation syndrome (OHSS). This occurs if too many follicles (>10 mm) are stimulated and results in abdominal distension, discomfort, nausea, vomiting and sometimes difficulty breathing. The mechanism for OHSS is thought to be secondary to activation of the ovarian renin-angiotensin pathway and excessive secretion of vascular epidermal growth factor (VEGF). The ascites, pleural and pericardial effusions exacerbate this serious condition and the resultant haemoconcentration can lead to thromboembolism. The situation worsens if a pregnancy has resulted from the treatment as hCG from the placenta further stimulates the ovaries. Hospitalization is sometimes necessary for intravenous fluids and heparin to be given to prevent dehydration and thromboembolism. Although the OHSS is rare it is potentially fatal and should be avoidable with appropriate monitoring of gonadotropin therapy. INSULIN-SENSITIZING AGENTS AND METFORMIN This biguanide inhibits the production of hepatic glucose and enhances the sensitivity of peripheral tissue to insulin, thereby decreasing insulin secretion. It has been shown that metformin ameliorates hyperandrogenism and abnormalities of gonadotropin secretion in women with PCOS and can restore menstrual cyclicity and fertility. Metformin therapy may be commenced after appropriate screening and advice about diet, lifestyle and exercise for anovulatory women with PCOS who have failed to conceive. The usual dose is either 850mgbd or 500mgtds. Baseline investigations should include an oral GTT, full blood count (FBC), urea and electrolytes (U&E) and liver function tests (LFTs). Side effects are predominantly gastrointestinal (anorexia, nausea, flatulence and diarrhoea) and may be reduced by taking metformin just before food and gradually increasing the dose from 850 mg once to 850 mg bd after 1 week. HYPERANDROGENISM AND HIRSUTISM Drug therapies may take 6–9 months or longer before any improvement of hirsutism is perceived. Physical treatments including electrolysis, waxing and bleaching may be helpful while waiting for medical treatments to work. Laser and photothermolysis techniques are more expensive but may have a longer duration of effect. The topical use of eflornithine may be effective. It works by inhibiting the enzyme ornithine decarboxylase in hair follicles and may be a useful therapy for those who wish to avoid hormonal treatments, but may also be used in conjunction with hormonal therapy. Eflornithine may cause some thinning of the skin and so high factor sun block is recommended when exposed to the sun. Medical regimens should stop further progression of hirsutism and decrease the rate of hair growth. Adequate contraception is important in women of reproductive age as transplacental passage of antiandrogens may disturb the genital development of a male fetus.  First line therapy has traditionally been the preparation Dianette, which contains ethinyloestradiol (30 μg) in combination with cyproterone acetate (2 mg).  Spironolactone is a weak diuretic with antiandrogenic properties and may be used in women in whom the COCP is contraindicated at a daily dose of 25– 100 mg. Drosperinone is a derivative of spironolactone and contained in the new COCP, Yasmin, which may also be beneficial for women with PCOS. Other antiandrogens such as ketoconazole, finasteride and flutamide have been tried, but are not widely used in the UK for the treatment of hirsutism in women due to their adverse side effects. Furthermore they are no more effective than cyproterone acetate. Thanks