Clinical, metabolic, and endocrine parameters in response to metformin and lifestyle intervention in women with polycystic ovary syndrome: A randomized, double-blind, and placebo control trial

Abstract

The aim of this study was to evaluate the effects of metformin in addition to diet and exercise on endocrine and metabolic disturbances in women with polycystic ovary syndrome (PCOS) in a prospective, double-blind, randomized, placebo (PBO) control trial. Thirty women with insulin resistance and PCOS received lifestyle modification and 1500 mg of metformin or placebo for 4 months. Before and after treatment, body mass index, waist/hip ratio, blood pressure, hirsutism, and menstrual patterns were evaluated. Serum concentrations of gonadotropins, androgens, progesterone, glucose, insulin, and lipids were measured. Lifestyle interventions resulted in similar weight and menstrual cycle's improvements in both groups. A significant reduction in serum fasting insulin, HOMA index, waist and testosterone levels was only observed with metformin. There were no significant changes in androstenedione, dehydroepiandrosterone sulfate, gonadotropins, and lipids levels. No other changes were observed in hirsutism or blood pressure. These findings suggest that metformin has an additive effect to diet and exercise to improve parameters of hyperandrogenism and insulin resistance. Although, a small decrease in body weight trough lifestyle changes could be enough to improve menstrual cycles in insulin-resistant women with PCOS.

Impact of hypocaloric dietary intervention on ovulation in obese women with PCOS

“…When one of these events occurred, the investigators scheduled a blood draw for serum progesterone based on an estimation of time to the next luteal phase (Crosignani et al , 2003; Qublan et al , 2007; Palomba et al , 2008; Kuchenbecker et al , 2011; Nybacka et al , 2011). Finally, of the remaining three studies, one did not provide adequate information with which to judge the frequency of measurements (Fux Otta et al , 2010) and two did not assess ovulation until after the intervention had ended (Guzick et al , 1994; Pasquali et al , 2011) (Table 2, Column 3).…”

“…In the interventions that assessed serum progesterone (Table 2, Column 2), ovulatory thresholds were always reported and ranged from ≥4 ng/ml (13 nmol/L) (Fux Otta et al , 2010) to ≥10 ng/ml (32 nmol/L) (Qublan et al , 2007; Palomba et al , 2008, 2010). It was difficult to discern whether these thresholds were internally validated or reflected the limits of detection of the various assays used.…”

“…In general, a serum progesterone concentration of 3.9 ng/ml (12.5 nmol/L) or higher is thought to be presumptive evidence of an ovulatory cycle using commonly available commercial assays (Wathen et al , 1984; Leiva et al , 2015). However, all of the studies identified thresholds for progesterone that were above this concentration (Guzick et al , 1994; Crosignani et al , 2003; van Dam et al , 2004; Qublan et al , 2007; Palomba et al , 2008, 2010; Fux Otta et al , 2010; Kuchenbecker et al , 2011; Pasquali et al , 2011). This is interesting, considering that the studies that relied on the highest thresholds (≥32 nmol/L) were also the ones to report the smallest proportion of responders to the dietary intervention (Qublan et al , 2007; Palomba et al , 2008, 2010) (Table 2, Column 6).…”

“…Among the studies that did, serum progesterone or urinary PDG were measured at a single time point (van Dam et al , 2004; Pasquali et al , 2011) or on a serial basis for up to two months prior to intervention (Guzick et al , 1994; Thomson et al , 2008, 2009). Alternatively, some participants were asked to keep menstrual diaries for one to six months (Moran et al , 2003, 2006, 2007b, Thomson et al , 2008, 2009; Fux Otta et al , 2010). While these direct and indirect markers of ovulation were likely used as a reference for improvement, only two of the studies actually published the data that were collected (Guzick et al , 1994; van Dam et al , 2004) (Table 2, Column 4).…”

Clomiphene citrate alternatives for the initial management of polycystic ovary syndrome: an evidence-based approach

“…Otta et al [40] in a randomized, double-blind and placebo control trial compared lifestyle modiWcation and 1,500 mg of metformin or placebo for 4 months in 30 women with insulin resistance PCOS. They reported that metformin has an additive eVect to diet and exercise to improve parameters of hyperandrogenism and insulin resistance.…”