PCO: Is treatment mandatory? Lebanese Society of Family Medicine 2010 PCOS An international consensus defined PCOS as having at least two of the following criteria: - Reduced or no ovulation. - Clinical or biochemical signs of excessive secretion of androgens; - Polycystic ovaries (the presence of at least 12 follicles measuring 2 to 9 mm in diameter, an ovarian volume of more than 10 ml, or both). PCOS manifestations • Infrequent or absent menses, obesity, and signs of androgen excess, which include acne or seborrhea • Should be considered in any adolescent girl with hirsutism, persistent acne, menstrual irregularity, or obesity • Commonly have insulin resistance, elevated serum LH levels PCOS- High risk groups • Women with oligo ovulatory infertility • Obesity and/or insulin resistance • Type 1, type 2, or gestational diabetes mellitus • A history of premature adrenarche • First-degree relatives with PCOS • Women using antiepileptic drugs : valproic acid ? PCOS associated morbidities • Increased risk of – Infertility – Metabolic syndrome – Type 2 diabetes mellitus – Probably cardiovascular disease – Probably endometrial carcinoma PCO and infertility • Many women having polycystic ovaries continue to ovulate • The high prevalence of this inherited condition indicates that it is not an absolute cause of infertility • If the circulating levels of FSH are within the normal range the follicles are healthy PCOS and Cardiovascular disease • Dyslipidaemia is the most common metabolic abnormality found in women with PCOS: – Elevated triglycerides, small low density lipoproteins (LDL) and reduced high density lipoprotein (HDL) – Increase of LDL size and the type III or type IV LDL subclasses: atherogenic LDL PCOS and CVD • Even if young and non-obese, PCOS women have a significant increase in cardiac size • Significantly lower left ventricular ejection fraction (LVEF) as a measure of systolic function, and reduced early atrial mitral flow velocity as a measure of diastolic function, although all patients have normal LVEF overall PCOS and CVD • Hyperinsulinaemia secondary to IR is a predictor of coronary artery disease, and IR has been proposed as the key factor linking hypertension, glucose intolerance, obesity, lipid abnormalities and coronary heart disease in 'metabolic syndrome ‘ • There are no long-term prospective data evaluating end-point morbidity and mortality for CVD in PCOS subjects. Is PCOS treatment mandatory? • What are treatment options PCOS treatment: Weight reduction • In obese women: decreases hirsutism, the production of ovarian androgens, and the conversion of androstenedione to testosterone • Low-CHO, a high protein/low CHO or a low protein/high CHO diets were equally effective for weight loss, improvements in menstrual cyclicity, insulin resistance, dyslipidemia, abdominal fat • Bariatric surgery PCOS treatments: Medical • There are several treatments for each of the symptoms of PCOS; the choice among them depends upon the woman's goals. • Drugs that decrease insulin levels can be effective in both obese and normal-weight women Treatment of PCOS • When no menstrual period for six or more weeks, withdrawal bleeding should be induced by administration of 5 to 10 mg of medroxyprogesterone acetate daily for 10 days prior to initiation of oral contraceptive treatment • Patients should be made aware that progestin therapy alone will not reduce the symptoms of acne or hirsutism, nor will it provide contraception PCOS and metformin • Is an alternative therapy that will restore ovulatory menses in approximately 50 percent of women with PCOS • Begin treatment with 500 mg taken with a meal, to reduce gastrointestinal side effects. • Clinically significant responses are not regularly observed at doses less than 1000 mg daily • When using extended release tablets, the entire daily dose is given at dinner time. valpic acid PCOS and metformin • Some women do not ovulate during the first six months of treatment. Unless cycles are regular and ovulatory, one cannot assume that the patient has reliable endometrial protection. Cyclic progestin is recommended • A contraceptive (eg, diaphragm, condom) should be prescribed for all sexually active women not planning pregnancy since treatment may induce ovulation PCOS and metformin • Improvement in plasma insulin and insulin sensitivity • Reduction in serum free testosterone independent of changes in body weight but no significant reduction in hirsutism • Increase in mean serum HDL cholesterol. Treatment for hirsutism • The main aim is to block or inhibit androgen production or action. Can be achieved using three groups of drugs: – Peripheral androgen blockers (e.g. cyproterone acetate, flutamide, or spironolactone) or antiandrogens (e.g. finasteride) – Insulin-sensitizing agents (e.g. rosiglitazone, metformin) – Inhibitors of androgen production e.g. oral contraceptives, GnRH analogues Hirsutism treatment • No systematic comparative trials, but there does not seem to be one agent clearly superior to the others. • Topical eflornithine 11·5% cream (Vaniqa®) may be used to inhibit hair growth. Eflornithine inhibits ornithine decarboxylase (ODC), a key enzyme of polyamine synthesis (responsible for cell proliferation, migration and differentiation). Treatment of hirsutism • The first-line therapy for treatment of hirsutism caused by PCOS is an estrogen- progestin contraceptive, as recommended by the 2008 Endocrine Society Guidelines. An antiandrogen is then added after six months if the cosmetic response is suboptimal. • OCPs given in oligomenorrhea but may worsen insulin resistance • Risk of thrombo embolic diseases Treatment of hirsutism • Typically start with a30 to 35 mcg OCP where the progestin has minimal androgenicity (such as norethindrone, norgestimate, desogestrel, or drospirenone). • After six months, if the patient is not satisfied with the clinical response, add Spironolactone 50 to 100 mg twice daily; this dose can then be reduced over time as needed. • Other antiandrogens that are effective include finasteride and cyproterone acetate Treatment of hirsutism • For women with hirsutism and contraindications to oral contraceptives, can sometimes use spironolactone alone • When spironolactone alone is used, endometrial protection is also needed. • Alternative form of contraception is essential Treatment of hirsutism • Leuprolide (Lupron Depot) 3.75 mg IM monthly until hot flashes appear when estrogen-progestin therapy should be initiated. • Increase leuprolide by 50 percent if hypoestrogenic state is not achieved by two months • Once a satisfactory dose has been achieved, estrogen-progestin therapy should be added Treatment of hirsutism • Reevaluate at regular intervals, and if after six months of therapy there has been no improvement in hirsutism, serum testosterone should be measured to determine the extent of ovarian suppression. • Generally not recommended in adolescents younger than 16 years of age PCO and anovulation • Initial steps: Weight loss through caloric restriction and increased exercise for women with a BMI >27 • Initial medical therapy includes metformin or clomiphene. Early ovulation induction trials reported better results with metformin alone or metformin plus clomiphene when compared to clomiphene alone • Metformin may be as effective for restoring ovulation, it appears to be less effective for fertility PCO and anovulation • A consensus group recommends: Clomiphene as the first-line drug for ovulation induction in women with PCOS, and metformin only in women with glucose intolerance • Approximately 80 percent of women with PCOS ovulate in response to clomiphene citrate, and approximately 50 percent conceive PCO and ovulation • Metformin may also modify the ovarian response in women with clomiphene- resistant PCOS undergoing ovulation induction with FSH (without IVF), with more orderly follicular growth , and a greater likelihood of mono-ovulatory cycles • Further study is needed to determine the role of metformin administration in women with PCOS undergoing IVF PCO and ovulation • Miscarriages occurred in 62 to 73 percent of pregnancies without metformin and 9 to 36 percent of pregnancies in the same women when metformin was taken • Although metformin is not FDA approved in pregnant women, there is some evidence to suggest that its use throughout pregnancy may reduce the risk of gestational diabetes • If medication is needed to treat gestational diabetes, insulin is the drug of choice, not an oral antihyperglycemic agent PCO and anovulation • Thiazolidinedione therapy may also be effective for induction of ovulation. • We do not suggest the routine use of these drugs, as concern has been raised about their cardiovascular safety • Laparoscopic ovarian laser electrocautery Is it mandatory to treat PCOS • Recognizing and treating PCOS are important beyond management of the presenting symptoms because PCOS increases the risk of developing endometrial hyperplasia and carcinoma, type 2 diabetes mellitus, metabolic syndrome, infertility, and possibly cardiovascular disease.
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