[Relationship between leptin and insulin sensitivity in patients with polycystic ovary syndrome]. / Relación entre leptina y sensibilidad a la insulina en mujeres con síndrome de ovario poliquístico.

BACKGROUND: The relationship between leptin and insulin sensitivity, sexual steroids and insulin concentrations in women with polycystic ovary syndrome is still controversial. The objective of this study was to assess the relationship between insulin levels, insulin resistance parameters and serum leptin concentrations in healthy and polycystic ovary syndrome women. PATIENTS AND METHODS: 33 hyperandrogenic polycystic ovary syndrome women (GHA) and 27 healthy women (GS) were included in this study. Leptin, insulin, sex-hormone binding globulin (SHBG), testosterone and estradiol concentrations were determined in a basal sample. Body mass index, waist diameter and waist to hip ratio were recorded. Insulin sensitivity was calculated by means of insulin tolerance test and glycemia/insulinemia ratio. RESULTS: The leptin concentration was not different between GHA and GS. Insulin levels and free testosterona index (FTI) were higher in GHA than GS (p < 0.01). The glycemia/insulinemia ratio, SHBG levels, and insulin sensitivity were lower in GHA (p < 0.01). In both groups positive correlations between leptin concentration and body mass index (p < 0.01), waist diameter (p < 0.01), insulin levels (p < 0.01) and glycemia/insulinemia ratio (p < 0.01) were observed. Only GHA showed correlation between insulin sensitivity and leptin concentration (p < 0.02). SHBG and leptin levels were not correlated. CONCLUSIONS: The leptin concentration was not different between GHA and healthy women, although they are metabolically different. This phenomenon could be due to the fact that in hyperandrogenic women the effects of insulin resistance and hyperandrogenemia counteract each other.

Are circulating leptin and luteinizing hormone synchronized in patients with polycystic ovary syndrome?

Animal and human studies suggest that leptin modulates hypothalamic-pituitary-gonadal axis functions. Leptin may stimulate gonadotrophin-releasing hormone (GnRH) release from the hypothalamus and luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from the pituitary. A synchronicity of LH and leptin pulses has been described in healthy women, suggesting that leptin probably also regulates the episodic secretion of LH. In some pathological conditions, such as polycystic ovarian syndrome (PCOS), LH-leptin interactions are not known. The aim of the present investigation was to assess the episodic fluctuations of circulating LH and leptin in PCOS patients compared to regularly menstruating women. Six PCOS patients and six normal cycling (NC) women of similar age and body mass index (BMI) were studied. To assess episodic hormone secretion, blood samples were collected at 10-min intervals for 6 h. LH and leptin concentrations were measured in all samples. For pulse analysis the cluster algorithm was used. To detect an interaction between LH and leptin pulses, an analysis of copulsatility was employed. LH concentrations were significantly higher in the PCOS group in comparison to NC women, however serum leptin concentrations and leptin pulse characteristics for PCOS patients did not differ from NC women. A strong synchronicity between LH and leptin pulses was observed in NC women; 11 coincident leptin pulses were counted with a phase shift of 0 min (P = 0.027), 18 pulses with a phase shift of -1 (P = 0.025) and 24 pulses with a phase shift of -2 (P = 0.028). PCOS patients also exhibited a synchronicity between LH and leptin pulses but weaker (only 20 of 39 pulses) and with a phase shift greater than in normal women, leptin pulses preceding LH pulses by 20 min (P = 0.0163). These results demonstrate that circulating leptin and LH are synchronized in normal women and patients with PCOS. The real significance of the apparent copulsatility between LH and leptin must be elucidated, as well as the mechanisms that account for the ultradian leptin release.

[Evaluation of acute effect of GnRH administration on leptin secretion in normal and hyperandrogenic women]. / Evaluación del efecto agudo de la administración de GnRH sobre la secreción de leptina en mujeres sanas e hiperandrogénicas.

BACKGROUND: Several studies suggest that leptin modulates the reproductive axis function. Leptin may stimulate release of GnRH from hypothalamus and of gonadotrophins from the pituitary. A synchronicity of LH and leptin pulses has been described in healthy women and in patients with polycystic ovarian syndrome (PCOS), suggesting a relationship between the episodic secretion of LH and leptin. In vitro experimental studies have demonstrated that leptin administration promotes GnRH-LH release. However it is not established whether GnRH promotes the episodic secretion of leptin. AIM: To assess the response of LH and leptin to the administration of a GnRH bolus in hyperandrogenic and healthy women. PATIENTS AND METHODS: Eleven hyperandrogenic and eleven healthy women of similar age and body mass index (BMI) were studied. Under basal conditions three blood samples were collected every 30 min before and after the administration of a GnRH bolus (100 micrograms). LH and leptin concentrations were measured in all samples. Testosterone, SHBG and estradiol were determined in the first sample. For data analysis, the increment of LH and leptin between 0-30 and 0-60 min was calculated. The LH and leptin areas under the curve (AUC) before and after GnRH administration were also calculated in both groups. RESULTS: After GnRH administration an increment in LH concentrations was observed in both groups; however, leptin concentrations were not modified. In both groups LH area under the curve increased after GnRH administration; however, the leptin area was not modified. CONCLUSIONS: These results suggest that circulating leptin concentration is not modulated by GnRH-LH.