You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
The effects of 17β-estradiol plus drospirenone on anthropometric and biochemical measures of adiposity in menopausal women
Abstract 1:
Purpose To assess whether there are changes on anthropometric and biochemical measures of adiposity in pre- and postmenopausal women and in the latter before and after 6 months treatment with 17β-estradiol plus drospirenone . Methods Twenty postmenopausal and 20 premenopausal women were enrolled in a prospect i ve comparative study . Postmenopausal women received 1 mg 17β-estradiol plus 2 mg drospirenone daily for 6 months . Measurements of body mass index ( BMI ) , waist/hip ratio and plasmatic levels of insulin , glucose , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , triglyceride , leptin , adiponectin , orexin-A , glucagon-like peptide-1 ( GLP-1 ) and ghrelin were performed in premenopausal ( group 1 ) and postmenopausal women and in the latter before ( group 2a ) and after ( group 2b ) 6 months treatment with 17β-estradiol plus drospirenone . Results No significant changes in BMI s , insulin and glucose were observed between group 1 and 2a ; and group 2a and 2b . GLP-1 levels were significantly increased in group 1 compared to group 2a ( p = 0.035 ) . Leptin levels were significantly increased ( p = 0.001 ) and GLP-1 levels were significantly decreased ( p = 0.021 ) in group 2b compared to group 2a . HDL was significantly decreased while LDL and triglyceride levels were significantly increased in group 2a compared to group 1 . ( p = 0.030 , p = 0.001 , p = 0.020 ; respectively ) LDL was significantly decreased ( p = 0.010 ) in group 2b compared to group 2a . GLP-1 had a positive correlation with orexin-A ( p < 0.001 , r = 0.520 ) and negative correlation with leptin ( p = 0.008 , r = −0.345 ) . Conclusion Leptin was significantly higher and GLP-1 was significantly lower in women receiving 17β-estradiol plus drospirenone treatment . GLP-1 levels were significantly lower after the menopause compared to premenopausal levels . Orexin-A and GLP-1 were positively correlated


Title 2:
Pulsatile LH release is diminished, whereas FSH secretion is normal, in hypocretin-deficient narcoleptic men.
Abstract 2:
Hypocretin ( orexin ) peptides are involved in the regulation of energy balance and pituitary hormone release . Narcolepsy is a sleep disorder characterized by disruption of hypocretin neurotransmission . Pituitary LH secretion is diminished in hypocretin-deficient animal models , and intracerebroventricular administration of hypocretin-1 activates the hypothalamo-pituitary-gonadal axis in rats . We evaluated whether hypocretin deficiency affects gonadotropin release in humans . To this end , we deconvolved 24-h serum concentrations of LH and FSH in seven hypocretin-deficient narcoleptic males ( N ) and seven controls ( C ) matched for age , body mass index , and sex .  Basal plasma concentrations of testosterone , estradiol , and sex hormone-binding globulin were similar in both groups . Mean 24-h LH concentration was significantly lower in narcolepsy patients [ 3.0 + /- 0.4 ( N ) vs. 4.2 + /- 0.3 ( C ) U/l , P = 0.01 ] , which was primarily due to a reduction of pulsatile LH secretion [ 23.5 + /- 1.6 ( N ) vs. 34.3 + /- 4.9 ( C ) U.l(-1).24 h(-1 ) , P = 0.02 ] . The orderliness of LH and FSH secretion , quantitated by the approximate entropy statistic , was greater in patients than in controls . In contrast , all other features of FSH release were similar in narcoleptic and control groups . Also , LH and FSH secretions in response to intravenous administration of 100 microg of GnRH were similar in patients and controls . These data indicate that endogenous hypocretins are involved in the regulation of the hypothalamo-pituitary-gonadal axis activity in humans . In particular , reduced LH release in the face of normal pituitary responsivity to GnRH stimulation in narcoleptic men suggests that hypocretins promote endogenous GnRH secretion


Title 3:
Serum orexin-A (OXA) level decreases in polycystic ovarian syndrome
Abstract 3:
Abstract Aim : In the current study , we aim ed to investigate whether serum orexin-A ( OXA ) levels are different in polycystic ovary syndrome ( PCOS ) subjects . Material s and methods : Thirty-six women with PCOS and 40 healthy , age and body mass index-matched controls were included in the prospect i ve cross-sectional study . All subjects underwent venous blood draws during the early follicular phase after overnight fasting .  Serum OXA levels were measured with an enzyme immunoassay ( EIA ) . The relationships between the serum OXA levels and the anthropometric and metabolic parameters were also assessed . Results : The serum OXA levels were lower in the women with PCOS compared to the control group . The serum OXA levels were correlated negatively with systolic blood pressure , the Ferriman-Gallway score and LH and free testosterone levels . Conclusion : Our results indicate that serum OXA levels decrease in the serum of women with PCOS


Title 4:
Glucose tolerance in patients with narcolepsy.
Abstract 4:
STUDY OBJECTIVES Obesity is a common feature of narcolepsy . In addition , an increased occurrence of non-insulin dependent diabetes has been reported . So far , it is not known whether glucose metabolism in narcolepsy is disturbed due to , or independently of obesity . DESIGN Case-control study . SETTING Sleep medicine clinic at a research institute . PATIENTS We studied 17 patients with narcolepsy/cataplexy compared to 17 healthy controls matched for age , sex , and body mass index ( BMI ) . INTERVENTIONS A 75-g oral glucose tolerance test was performed . MEASUREMENTS Glucose tolerance was determined by computing plasma glucose curve following oral glucose challenge for 240 minutes ; insulin sensitivity and insulin secretion by homeostasis model assessment and minimal model analysis . RESULTS St and ard outcome measures and indices of the oral glucose tolerance test did not differ between the patient group and the group of control subjects . CONCLUSIONS In this study , no clinical ly relevant pathologic findings in the glucose metabolism of narcoleptic patients compared to weight matched controls were found . Thus , narcolepsy is unlikely to be a risk factor per se for impaired glucose tolerance or diabetes


Title 5:
Plasma orexin A levels in recently menopausal women during and 3 years following use of hormone therapy.
Abstract 5:
OBJECTIVE Alterations in sleep quality and metabolism during menopause are improved by menopausal hormone therapy ( MHT ) . The mechanisms mediating these effects remain unclear . Orexin A ( OxA ) is a neuro-peptide that regulates sleep/wakefulness , food intake and metabolism . This study examined changes in plasma OxA levels during and after treatment in women from the Kronos Early Estrogen Prevention Study ( KEEPS ) . METHODS KEEPS r and omized women within three years of menopause to : oral conjugated equine estrogen ( o-CEE , 0.45mg/day ) , transdermal 17β estradiol ( t-E2 , 50μg/day ) , or placebo pills and patches for four years  . Plasma OxA levels were measured by enzyme immunoassays in fasting blood sample s collected annually from KEEPS participants at Mayo Clinic during and three years after MHT .  Changes in menopausal symptoms and plasma OxA levels were assessed for treatment differences . RESULTS During treatment , OxA levels increased more in women r and omized to o-CEE compared with the other groups . Women r and omized to either form of MHT demonstrated smaller increases in BMI than those on placebo . Insomnia severity decreased similarly among treatment groups . However , neither changes in sleep nor changes in BMI correlated with changes in plasma OxA levels . Changes in waist circumference correlated positively with changes in plasma OxA levels three years after discontinuation of study treatments . CONCLUSIONS Although OxA levels increased only in women r and omized to o-CEE , these changes did not correlate with changes in sleep quality or BMI . The modest correlation of OxA levels with waist circumference once study treatments were discontinued suggests that OxA may be modulated through multiple intermediary pathways affected by metabolites of 17β-estradiol . Clinical Trial Registration for KEEPS : NCT00154180


Title 6:
Inverse Association of Peripheral Orexin-A with Insulin Resistance in Type 2 Diabetes Mellitus: A Randomized Clinical Trial.
Abstract 6:
AIMS To investigate the association between serum orexin concentrations and insulin resistance/sensitivity in a sample of patients with type 2 diabetes mellitus , and to study the effects of anti-hyperglycemic treatment on orexin concentrations over three months . METHODS This study was design ed as a r and omized , open-label , clinical trial . Before allocation , sixty medication-naïve , newly-diagnosed , type 2 diabetes patients underwent a 75 g oral glucose tolerance test ( OGTT ) . Afterwards , using a r and omized trial design ( I RCT 201102275917N1 ) patients were allocated to either the metformin ( 1000 mg daily ) or pioglitazone ( 30 mg daily ) arm , and were reexamined after three months . Serum insulin , plasma glucose , and orexin concentrations were measured at baseline , during OGTT , and after three months . RESULTS Orexin concentrations significantly decreased after OGTT ( 0 vs. 120 min : 0.63 ± 0.07 vs. 0.31 ± 0.03 ng/ml , p < 0.001 ) . Insulin resistance determined by homeostasis model assessment of insulin resistance ( HOMA-IR ) was significantly and negatively correlated with orexin ( r = -0.301 , p = 0.024 ) . Furthermore , orexin concentrations were significantly and positively correlated with the insulin sensitivity index derived from OGTT ( r = 0.326 , p = 0.014 ) . Three-month treatment with metformin and pioglitazone significantly improved insulin sensitivity and increased orexin concentrations by 26 % ( p = 0.025 ) and 14 % ( p = 0.076 ) , respectively . Between-group analysis showed that changes in orexin concentrations  with metformin and pioglitazone were not significantly different ( p = 0.742 ) . CONCLUSIONS There was a negative association between peripheral orexin concentrations and insulin resistance in type 2 diabetes patients . Three-month anti-hyperglycemic treatment with proportionate doses of metformin or pioglitazone  increased orexin concentrations via amelioration of insulin resistance and improvement of glycemic control


Title 7:
Associations of snoring frequency and intensity in pregnancy with time‐to‐delivery
Abstract 7:
BACKGROUND Sleep-disordered breathing ( SDB ) is linked to adverse pregnancy outcomes . However , little is known about the association of SDB with timing of delivery . We examined the association of snoring frequency , a key SDB marker , and snoring intensity , a correlate of SDB severity , with time-to-delivery among a cohort of pregnant women . METHODS In this prospect i ve cohort study , 1483 third trimester pregnant women were recruited from the University of Michigan prenatal clinics . Women completed a question naire about their sleep , and demographic and pregnancy information was abstract ed from medical charts . After exclusion of those with hypertension or diabetes , 954 women were classified into two groups by their snoring onset timing , chronic or pregnancy-onset . Within each of these groups , women were divided into four groups based on their snoring frequency and intensity : non-snorers ; infrequent-quiet ; frequent-quiet ; or frequent-loud snorers . Cox proportional hazard regression models were used to investigate the association between snoring frequency and intensity and time-to-delivery , adjusting for maternal characteristics . RESULTS Chronic snoring was reported by half of the pregnant women , and of those , 7 % were frequent-loud snorers . Deliveries before 38 weeks ' gestation are completed occurred among 25 % of women with chronic , frequent-loud snoring . Compared with pre-pregnancy non-snorers , women with chronic frequent-loud snoring had an increased hazard ratio for delivery ( adjusted hazard ratio 1.60 , 95 % confidence interval 1.04 , 2.45 ) . CONCLUSIONS Snoring frequency and intensity is associated with time-to-delivery in women absent of hypertension or diabetes . Frequent-loud snoring may have a clinical utility to identify otherwise low-risk women who are likely to deliver earlier
Associations between HCRT1 , metabolic and reproductive function are inconsistent .