Effect of Long-Term Treatment with Metformin Added to Hypocaloric Diet on Body Composition, Fat Distribution, and Androgen and Insulin Levels in Abdominally Obese Women with and without the Polycystic Ovary Syndrome

Abstract

Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo). The treatment was well tolerated. In the PCOS group, metformin therapy improved hirsutism and menstrual cycles significantly more than placebo. Baseline anthropometric and CT parameters were similar in all groups. Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups, without any significant effect on CT scan parameters. In both PCOS and control women, however, metformin treatment reduced body weight and BMI significantly more than placebo. Changes in the waist-to-hip ratio values were similar in PCOS women and controls, regardless of pharmacological treatment. Metformin treatment significantly decreased SAT values in both PCOS and control groups, although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment. On the contrary, visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups, but only in the former was the effect of metformin treatment significantly higher than that of placebo. F...

Factors associated with percent change in visceral versus subcutaneous abdominal fat during weight loss: findings from a systematic review

“…Unfortunately, only one study of LCD and one of LCD þ sibutramine provide data at 4 weeks for comparison. 16,59 These studies show only mild %dV/%dS (1.28 and 1.39) at this time point, suggesting that early elevated %dV/%dS is associated with VLCDs. Interestingly, among studies in which subjects were followed up after 12-14 weeks, VLCDs had caused greater weight loss and lower %dV/%dS than other studies at this time point (Figure 3).…”

Metformin and body weight

“…80 Weight, waist and BMI were reduced in all groups (Po0.0001). Small 7-month studies in nondiabetic overweight (BMI 428 kg/m 2 ) 81 or morbidly obese subjects (mean BMI 43 kg/m 2 ) 82 demonstrated decreases in body weight with metformin, although only the latter study demonstrated a reduction in waist circumference. Two of the studies summarized in Table 3 suggest a greater weight reduction with metformin relative to placebo, but these differences did not achieve statistical significance.…”

“…[79][80][81][82] The first Biguanides and Prevention of the Risks in Obesity study 1 enrolled 324 patients with abdominal obesity (waist-hip ratio X0.95 in men and X0.80 in women) in order to recruit a trial population containing a high prevalence of insulin resistance. 79 Subjects were also free of cardiovascular disease and diabetes at baseline.…”

“…90 Details of trials of at least 6 months' duration are shown in Table 5. 81,[91][92][93][94] In general, these were well designed, randomized studies (evidence level A). However, one study 92 randomized patients to one of two doses of metformin, without a non-metformin control group, and was thus categorized as evidence level C for the purposes of this review.…”

Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling

“…PCOS is a heterogeneous disorder, characterised by hyperandrogenism, chronic anovulation and infertility [2][3][4][5]. A significant proportion of PCOS women suffer from insulin resistance, which appears to play a role in the aetiology of PCOS, since amelioration of insulin resistance by lifestyle or pharmacological intervention has been shown to improve hyperandrogenism and fertility [6][7][8][9]. Furthermore, insulin resistance is proposed to be a major risk factor for the development of type 2 diabetes mellitus and subsequent cardiovascular disease [10][11][12][13].…”