Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome

Abstract

The causes of luteal phase progesterone deficiency in polycystic ovary syndrome (PCOS) are not known. To determine the possible involvement of hyperinsulinemia in luteal phase progesterone deficiency in women with PCOS, we examined the relationship between progesterone, luteinizing hormone (LH) and insulin during the luteal phase and studied the effect of metformin on luteal progesterone levels in PCOS. Patients with PCOS (19 women aged 18-35 years) were treated with metformin (500 mg three times daily) for 4 weeks prior to the test cycle and throughout the study period, and submitted to ovulation induction with clomiphene citrate. Blood samples were collected from control (N = 5, same age range as PCOS women) and PCOS women during the late follicular (one sample) and luteal (3 samples) phases and LH, insulin and progesterone concentrations were determined. Results were analyzed by one-way analysis of variance (ANOVA), Duncan's test and Karl Pearson's coefficient of correlation (r). The endocrine study showed low progesterone level (4.9 ng/ml) during luteal phase in the PCOS women as compared with control (21.6 ng/ml). A significant negative correlation was observed between insulin and progesterone (r = -0.60; P < 0.01) and between progesterone and LH (r = -0.56; P < 0.05) concentrations, and a positive correlation (r = 0.83; P < 0.001) was observed between LH and insulin. The study further demonstrated a significant enhancement in luteal progesterone concentration (16.97 ng/ml) in PCOS women treated with metformin. The results suggest that hyperinsulinemia/insulin resistance may be responsible for low progesterone levels during the luteal phase in PCOS. The luteal progesterone level may be enhanced in PCOS by decreasing insulin secretion with metformin.

Effects of metformin on the glycemic control, lipid profile, and arterial blood pressure of type 2 diabetic patients with metabolic syndrome already on insulin

“…However, metformin is known to positively affect other parameters which influence the development of cardiovascular disease, regardless of any effect on BP (30,31). Our results agree with the literature regarding the effect of metformin on BMI reduction (9,12,13), reduction of daily insulin dose (9,12,13), biguanide-related sideeffects (21,24), and reduction of WC, which is a cornerstone for the diagnosis of metabolic syndrome and may play the role of a co-variate when other parameters are analyzed (18,32).…”

Effect of DHEA and metformin on corpus luteum in mice

“…In agreement with these findings, it has been reported that women with PCOS show lower levels of P in the early luteal phase when compared to healthy controls (Joseph-Horne et al 2002, Lunn et al 2002. Moreover, the inability of women with PCOS to sustain early pregnancy is correlated to the decrease in ovarian steroidogenesis during the luteal phase (Franks 1995, Meenakumari et al 2004). …”

“…Controversial results have been reported on the action of metformin in modulating ovarian steroidogenesis during the luteal phase. While Meenakumari et al (2004) demonstrated that metformin restores P levels during the functional stage of CL development in PCOS patients, Vrbíková et al (2001) reported no significant changes in basal steroid production. Our results are in agreement with those reported by Tosca et al (2006b), who found that metformin increases E 2 secretion of no-stimulated granulose cells.…”

Dual targeting of TNF-αand free radical toxic stress as a promising strategy to manage experimental polycystic ovary

“…Moreover, decreased rate of normal ovulations or anovulation and lack of developing CL have been shown to lead to decreased serum progesterone concentrations in the present model, as also seen in PCOS women (Meenakumari et al, 2004). Such a hormonal disturbance was expected, which in turn led to constant estrus manifestation in PCO rats.…”