Augmented frequency and mass of LH discharged per burst are accompanied by marked disorderliness of LH secretion in adolescents with polycystic ovary syndrome

Abstract

The aim of this study was to quantify pulsatile LH secretion, burst frequency and mass, LH half-life, and the approximate entropy (ApEn) or (dis-) orderliness of LH release in adolescents with polycystic ovary syndrome (PCOS), combining a high-precision immunofluorimetric LH assay with deconvolution techniques.We sampled LH concentration profiles every 20 min overnight in 12 girls with PCOS (mean Ϯ S.E.M. age 16.4 Ϯ 0.57 years, body mass index (BMI) 24.4 Ϯ 1.6 kg/m 2 ) and 11 eumenorrheic earlyfollicular-phase controls (mean Ϯ S.E.M. age 16.5 Ϯ 0.47 years, BMI 22.2 Ϯ 1.0 kg/m 2 ). Fasting serum levels of androstenedione, testosterone, 17-hydroxyprogesterone (17-OHP), estrone. estradiol, FSH and sex hormone-binding globulin (SHBG) were determined. Compared with euandrogenic girls, PCOS adolescents had significantly (P < 0.005) elevated serum LH/FSH ratios, 17-OHP, androstenedione, esterone and testosterone levels, decreased SHBG, and similar estradiol. PCOS subjects exhibited a 3-fold higher mean serum LH concentration with almost no overlap with controls (8.8 Ϯ 1.2 and 2.8 Ϯ 0.3 IU/l respectively, P < 0.001). We initially used a conventional serum hormone concentration peak analysis method (Cluster) to evaluate the characteristics of pulsatile LH release. Cluster analysis disclosed a significant increase in serum LH concentration maximal peak height, a higher LH peak frequency and a higher mean serum LH concentration in interpulse nadirs in the PCOS group. Deconvolution analysis of mechanisms underlying the foregoing showed higher frequency in the PCOS group than the controls (7.9 Ϯ 0.4 and 5.7 Ϯ 0.6 pulses/12 h respectively, P < 0.05). The mass of LH released per secretory event was also significantly higher in PCOS subjects than controls (5.4 Ϯ 0.57 and 3.4 Ϯ 0.56 IU/l respectively, P < 0.05). Since the pulsatile production rate is the product of the mean mass of hormone secreted per pulse and the number of pulses per day, we estimated a significantly higher mean pulsatile production rate of (endogenous) LH in the PCOS group (41 Ϯ 4.2 IU/l per day in the PCOS group vs 18 Ϯ 2.3 IU/l per day in the controls, P < 0.01). The mean estimated half-life of endogenous LH disappearance was also significantly higher in patients with PCOS than in controls (110 Ϯ 8.5 and 77 Ϯ 3.7 min respectively, P < 0.01). To quantify the orderliness of LH release, we used ApEn. PCOS patients had remarkably increased disorderliness (higher ApEn) of LH release (1.09 Ϯ 0.04 vs 0.77 Ϯ 0.08 in controls, P ¼ 0.002). Mean serum LH concentration, mass of LH secreted per burst, and LH production rate in PCOS, but not in normal adolescents, correlated positively with androstenedione (P < 0.02, 0.02 and 0.05 respectively). The same parameters also correlated positively with 17-OHP (P < 0.05, 0.02 and 0.05 respectively). Stepwise regression analysis unmasked a negative influence of BMI in PCOS on both mass of LH secreted per burst (r ¼ ¹0.77, P < 0.005) and LH production rate (r ¼ ¹0.70, P < 0.01). We conclude that PCOS adolescents secrete ...

Acceleration of Luteinizing Hormone Pulse Frequency in Adolescent Girls with a History of Central Precocious Puberty with versus without Hyperandrogenism

“…In addition, during the night, CPPA patients showed a higher, although nonsignificant, ApEn of LH release (increased disorderliness) than CPPB girls and healthy controls. All these findings resemble the alterations in LH secretory dynamics we previously described in adolescents girls with PCOS [6]. The LH pattern of hypersecretion and increased pulsatility during the night as well as during the day is similar to that reported by Apter et al [28] on hyperandrogenic adolescents who had a comparable chronological and gynaecological age to our patients, studied with the same LH assay (IFMA).…”

“…LH concentrations are commonly increased, whereas FSH concentrations fall within the low follicular range. Recent analyses provide evidence that elevated LH concentrations in PCOS adolescents arise from an increased frequency and mass of LH secreted per burst [6]. …”

“…Recently we have demonstrated that PCOS adolescents display a hormonal profile similar to that in PCOS women [namely high serum luteinizing hormone (LH), testosterone, androstenedione and estrone concentrations] [6]. This studyidentified accelerated frequency and augmented mass of LH discharged per burst along with marked disorderliness of LH secretion in PCOS adolescents compared with normal girls, using highly specific LH immunofluorometric assay (IFMA), deconvolution analysis to estimate LH secretory properties and approximate entropy (ApEn) to assess the orderliness of LH release [6].…”

“…This studyidentified accelerated frequency and augmented mass of LH discharged per burst along with marked disorderliness of LH secretion in PCOS adolescents compared with normal girls, using highly specific LH immunofluorometric assay (IFMA), deconvolution analysis to estimate LH secretory properties and approximate entropy (ApEn) to assess the orderliness of LH release [6]. …”

Exaggerated 17-hydroxyprogesterone response to intravenous infusions of recombinant human LH in women with polycystic ovary syndrome

“…ovarian steroidogenesis; hyperandrogenism; androstenedione; testosterone; 17-hydroxyprogesterone; luteinizing hormone THE ETIOLOGY OF OVARIAN HYPERANDROGENEMIA in the polycystic ovary syndrome (PCOS) remains enigmatic. Previous studies have emphasized the relative roles of neuroendocrine abnormalities leading to persistent and excessive LH secretion (11,14,20,30,34) and the ovarian actions of hyperinsulinemia, a consequence of insulin resistance (4,27,35,40). Additional evidence suggests that anomalous ovarian steroidogenesis is a primary abnormality in PCOS.…”