Week 6 - Part 1 - Polycystic Ovarian Syndrome.pdf

WEEK 6: POLYCYSTIC OVARIAN SYNDROME (PCOS) EHR522: EXERCISE FOR METABOLIC AND MENTAL HEALTH CONDITIONS Subject Coordinator: Tim Miller [email protected] 02 6338 4442 POLYCYSTIC OVARIAN SYNDROME (PCOS)  Polycystic ovarian syndrome (PCOS) is...

WEEK 6: POLYCYSTIC OVARIAN SYNDROME (PCOS) EHR522: EXERCISE FOR METABOLIC AND MENTAL HEALTH CONDITIONS Subject Coordinator: Tim Miller [email protected] 02 6338 4442 POLYCYSTIC OVARIAN SYNDROME (PCOS)  Polycystic ovarian syndrome (PCOS) is an endocrinopathy of uncertain aetiology  Prevalence estimates vary based upon the diagnostic criteria used, but range from 4 – 20% of women of reproductive age  The many features of PCOS can be broadly divided into three categories  Clinical  Endocrine  Metabolic PCOS – CLINICAL FEATURES  Clinical features include  Menstrual abnormalities (oligomennorhea or amenorrhea)  Hirsutism  Acne  Alopecia  Anovulatory infertility  Recurrent miscarriages PCOS – ENDOCRINE FEATURES  Endocrine features include elevated  Androgens  Luteinising hormone  Oestrogen  Prolactin PCOS – METABOLIC FEATURES  Metabolic features often include  Insulin resistance  Obesity  Lipid abnormalities  Increased risk for impaired glucose tolerance and T2DM PCOS – PREVALENCE OF COMMON FEATURES  Menstrual disturbances commonly observed in PCOS include oligomenorrhea, amenorrhea and prolonged erratic menstrual bleeding. However, 30% of women with PCOS have normal menses  Approximately 85 – 90% of women with oligomenorrhea have PCOS, while 30 – 40% of women with amenorrhea have PCOS  Infertility affects 40% of women with PCOS  Approximately 90 – 95% of anovulatory women presenting to infertility clinics have PCOS  Spontaneous abortion occurs more frequently in PCOS with incidence ranging from 42 – 73% PCOS – RISK FACTORS  Risk factors for PCOS in adults include:  T1DM  T2DM  GDM PCOS – COMMON COMORBIDITIES  Insulin resistance affects 50 – 70% of women with PCOS leading to a number of comorbidities, including  Metabolic syndrome  Hypertension  Dyslipidaemia  Glucose intolerance  Diabetes  Women with PCOS are more likely to have increased coronary artery calcium scores PCOS – COMMON COMORBIDITIES  Mental health disorders occur more frequently in women with PCOS. These include  Depression  Anxiety  Bipolar disorder  Binge eating disorder PCOS – DIAGNOSTIC CRITERIA  Controversy exists regarding the criteria used for PCOS diagnosis  Diagnosis of PCOS requires at least two of the following characteristics, in the absence of other causes, including pituitary and adrenal dysfunction  Clinical or biochemical hyperandrogenism  Anovulatory menstrual dysfunction  Polycystic ovaries on ultrasound PCOS – DIAGNOSTIC CRITERIA  Although not included in the diagnostic criteria, insulin resistance, underpinned by insulin signalling pathway defects, is strongly implicated in the aetiology of PCOS  The polycystic ovary morphology is consistent with, but not essential for, the diagnosis of the syndrome PCOS – PATHOPHYSIOLOGY  A complete explanation of the pathophysiology of PCOS is lacking. The heterogeneity of PCOS may in fact represent multiple pathophysiological mechanisms  Several theories have been proposed to explain the pathogenesis of PCOS  A unique defect in insulin action and secretion that leads to hyperinsulinaemia and insulin resistance  A primary neuroendocrine defect leading to an exaggerated luteinising hormone pulse frequency and amplitude  A defect of androgen synthesis that results in enhanced ovarian androgen production  An alteration in cortisol metabolism resulting in enhanced adrenal androgen production PCOS – PATHOPHYSIOLOGY  A familial pattern in some cases suggests a genetic component, but the candidate genes are yet to be identified  There are links between PCOS and endometrial cancer, obesity, cardiovascular disease and diabetes mellitus with both short- and long-term consequences PCOS – ECONOMIC BURDEN  PCOS costs the USA healthcare system $4.4 billion annually  40% is attributed to treating reproductive dysfunction (infertility and menstrual dysfunction)  40% is attributed to PCOS-related diabetes PCOS – PHARMACEUTICAL INTERVENTION  Pharmaceutical treatment for PCOS focuses primarily on addressing reproductive dysfunction and insulin resistance  Oral contraceptives are used to treat menstrual irregularity, hirsutism and acne. Long-term use of oral contraceptives, however, remain controversial from a cardiometabolic standpoint  Spironolactone (aldosterone antagonist) and finasteride (5-alpha reductase inhibitor) are used to treat symptoms of androgen excess PCOS – PHARMACEUTICAL INTERVENTION  Fertility treatments for PCOS include ovulation induction agents (such as Clomiphene Citrate)  Second-line fertility therapies include exogenous gonadotropins, laparoscopic ovarian drilling and assisted reproductive technology  Metformin is commonly used to improve insulin resistance, which can in turn play a role in ovulation induction  There is currently no ideal pharmacological intervention in PCOS and for this reason exercise, dietary modification and weight remain first-line management strategies to improve cardiovascular risk factors and reproductive dysfunction PCOS – EXERCISE INTERVENTION  There are currently no evidence-based exercise guidelines for the treatment of PCOS  Exercise prescription should therefore be individualised to the patient based upon presentation and clinical features/comorbidities PCOS – THE EVIDENCE FOR EXERCISE  Exercise intervention in women with PCOS has been shown to  Increase follicle-stimulating hormone  Increase sex hormone-binding globulin  Decrease total testosterone  Decrease androstenedione PCOS – THE EVIDENCE FOR EXERCISE - WEIGHT  Due to a complex physiological interplay, many women with PCOS find it difficult to lose weight  Nonetheless, in women who do lose weight, the traditional exercise approach to the management of overweight and obese individuals is typically most successful PCOS – THE EVIDENCE FOR EXERCISE – INSULIN RESISTANCE  Insulin resistance in PCOS is unique, being intrinsically present in the majority of lean PCOS women and further exacerbated by extrinsic obesity-related insulin resistance, however the mechanisms underlying insulin resistance are yet to be fully elucidated  Approximately half of the available studies in women with PCOS demonstrate an improvement in insulin resistance with an exercise intervention  PCOS patients with insulin resistance should be managed as you would manage a patient with pre- diabetes or T2DM managed through lifestyle approaches PCOS – THE EVIDENCE FOR EXERCISE – BLOOD LIPIDS  The majority of the available studies in women with PCOS have not shown a reduction in blood lipids with exercise intervention  A limited number of studies however have demonstrated improvements in triglycerides, HDLc and LDLc with exercise intervention in women with PCOS PCOS – THE EVIDENCE FOR EXERCISE – BLOOD PRESSURE  Approximately half of the available evidence suggests that exercise interventions in women with PCOS can reduce either systolic or diastolic blood pressure PCOS – THE EVIDENCE FOR EXERCISE – REPRODUCTIVE FUNCTION  Of five available studies reporting on menstrual function in women with PCOS, three reported improvements in menstrual and/or ovulation frequency following exercise  The improvement in reproductive function was not dependent on the length of the intervention or the type of exercise performed  Exercise appears significantly more potent than dietary intervention in improving reproductive function in women with PCOS PCOS – THE EVIDENCE FOR EXERCISE – SUMMARY  Despite the lack of well designed studies, lifestyle intervention, including exercise, is first-line therapy in the majority of women with PCOS  All studies that had successful outcomes with women with PCOS included moderate intensity supervised exercise (60 – 70% VO2max or HRR; 75 – 80% HR max) and reported improvements within 12 weeks of exercise, regardless of study duration  The most consistent improvements were demonstrated in  Weight loss  Insulin resistance  Reproductive function PCOS – THE EVIDENCE FOR EXERCISE – SUMMARY  Insulin resistance underpins many of the clinical features and should therefore be a treatment target in PCOS  Enhanced insulin sensitivity underpins restoration of reproductive function through hormonal improvements, including reduced androgens PCOS – THE EVIDENCE FOR EXERCISE – SUMMARY  Based on the results of the available studies, women with PCOS should be advised to engage in at least 90 minutes of aerobic activity per week at a moderate intensity to achieve improved reproductive and cardiometabolic outcomes  However, given the considerable variability in the design, intensity and outcome measures of the available studies, it is very difficult to make specific recommendations  Each patient should be treated as an individual with consideration being given to their presenting clinical features and comorbidities