Effect of lifestyle intervention on the reproductive endocrine profile in women with polycystic ovarian syndrome: a systematic review and meta-analysis

摘要

Polycystic ovarian syndrome (PCOS) affects 18–22% of women at reproductive age. We conducted a systematic review and meta-analysis evaluating the expected benefits of lifestyle (exercise plus diet) interventions on the reproductive endocrine profile in women with PCOS. Potential studies were identified by systematically searching PubMed, CINAHL and the Cochrane Controlled Trials Registry (1966–April 30, 2013) systematically using key concepts of PCOS. Significant improvements were seen in women receiving lifestyle intervention vs usual care in follicle-stimulating hormone (FSH) levels, mean difference (MD) 0.39?IU/l (95% CI 0.09 to 0.70, P =0.01), sex hormone-binding globulin (SHBG) levels, MD 2.37?nmol/l (95% CI 1.27 to 3.47, P <0.0001), total testosterone levels, MD ?0.13?nmol/l (95% CI ?0.22 to ?0.03, P =0.008), androstenedione levels, MD ?0.09?ng/dl (95% CI ?0.15 to ?0.03, P =0.005), free androgen index (FAI) levels, MD ?1.64 (95% CI ?2.94 to ?0.35, P =0.01) and Ferriman–Gallwey (FG) score, MD ?1.01 (95% CI ?1.54 to ?0.48, P =0.0002). Significant improvements were also observed in women who received exercise-alone intervention vs usual care in FSH levels, MD 0.42?IU/l (95% CI 0.11 to 0.73, P =0.009), SHBG levels, MD 3.42?nmol/l (95% CI 0.11 to 6.73, P =0.04), total testosterone levels, MD ?0.16?nmol/l (95% CI ?0.29 to ?0.04, P =0.01), androstenedione levels, MD ?0.09?ng/dl (95% CI ?0.16 to ?0.03, P =0.004) and FG score, MD ?1.13 (95% CI ?1.88 to ?0.38, P =0.003). Our analyses suggest that lifestyle (diet and exercise) intervention improves levels of FSH, SHBG, total testosterone, androstenedione and FAI, and FG score in women with PCOS. Keywords: exercise, follicle-stimulating hormone, luteinizing hormone, insulin resistance, female reproduction, polycystic ovarian syndromeIntroductionPolycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder, affecting 18–22% of reproductive-age women (1). PCOS was first reported in 1935 by Stein & Leventhal (2) and is characterised by clinical or biochemical hyperandrogenism (clinical manifestations are hirsutism, android alopecia and acne), oligo/amenorrhoea (infrequent or no menstruation), polycystic ovaries and infertility or reduced fertility (3, 4). Often women with PCOS are obese, which contributes to insulin resistance and hyperinsulinaemia, but these two features are also present in lean women with PCOS (5, 6). Hormonal manifestations include elevated levels of androgens (testosterone, DHEA and androstenedione), oestrogens and prolactin. Occasionally, thyroid-stimulating hormone levels are also lower leading to hypothyroidism (7). Most women with PCOS have elevated luteinising hormone (LH) levels and reduced follicle-stimulating hormone (FSH) levels particularly during the follicular phase of the menstrual cycle (8). The elevated LH level probably increases the follicular androgen concentrations leading to follicular arrest and the reduced FSH concentrations lead to an accumulation of small follicles (9). The resultant oestrogen environment alters the hypothalamic release of gonadotrophin-releasing hormone and leads to an increase in LH secretion and suppression of FSH secretion by the pituitary (8, 10). This altered LH:FSH ratio is used as a diagnostic criterion for this condition, but it is not universally present (11).The levels of sex hormone-binding globulin (SHBG), the primary plasma transport system which controls the availability of androgens, are reduced in women with PCOS leading to an increase in free testosterone levels contributing to the free androgen index (FAI) (12). Owing to the effects of insulin on hepatic SHBG production, insulin insensitivity may affect ovulation and fertility. Dyslipidaemia, increased insulin levels, obesity, hypertension, impaired glucose tolerance and insulin-induced metabolic syndrome are also the risk factors that can predispose women with PCOS to cardiovascular disease and type 2 diabetes mellitus (6).A systematic review was completed in 2011 by Harrison et al . (13), but presumably as insufficient data were available at that time, these authors did not conduct data pooled analyses. A systematic review and subsequent meta-analyses were conducted by Moran et al . (14), but these analyses included only six published studies with slightly different inclusion/exclusion criteria. However, our work provides a greater number of hormonal analyses when compared with Moran's work (14). We therefore conducted a systematic review and meta-analysis, and the primary aim was to evaluate the expected benefits of exercise training and dietary interventions on a range of endocrinal outcomes in women with PCOS.Subjects and methodsSearch strategyPotential studies were identified by conducting a systematic search using PubMed (www.ncbi.nlm.nih.gov/pubmed; 1966–April 30, 2013). CINAHL and the Cochrane Controlled Trials Registry were also used for the search (1966–April 30, 2013). The search strategy included the key con