bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Prospective Randomized Trial Comparing Low Dose Flutamide, Finasteride, Ketoconazole, and Cyproterone Acetate-Estrogen Regimens in the Treatment of Hirsutism
Authors: Venturoli S. , Marescalchi O. , Colombo F. M. , Macrelli S. , Ravaioli B. , Bagnoli A. , Paradisi R. , Flamigni C. 
Published: January 2014

Sixty-six hirsute women were randomized and treated with 1) flutamide (n = 15), 250 mg/day; 2) finasteride (n = 15), 5 mg/day; 3) ketoconazole (n = 16), 300 mg/day; and 4) ethinyl estradiol (EE)-cyproterone acetate (CPA; n = 20), 0.01 mg EE/day for the first week, 0.02 mg EE/day for the second week, and 0.01 mg EE/day for the third week, followed by a pause of 7 days, then 12.5 mg CPA/day added during the first 10 days of every month for 12 months. Hirsutism was evaluated by the Ferriman-Gallwey score, and hair diameter and hair growth rate were determined by a special image analysis processor in basal conditions and after 90, 180, 270, and 360 days of treatment. All treatments produced a significant decrease in the hirsutism score, hair diameter, and daily hair growth rate: flutamide, −55 ± 13%, −21 ± 14%, and −37 ± 18%; finasteride, −44 ± 13%, −16 ± 12%, and− 27 ± 14%; ketoconazole, −53 ± 18%, −14 ± 12%, and −30 ± 21%; and EE-CPA, −60 ± 18%, −20 ± 11%, and −28 ± 21%.Some differences existed among treatments with regard to effectiveness; EE-CPA and flutamide seem to be the most efficacious in improving hirsutism. For the hirsutism score, a greater decrease was seen with EE-CPA (−60 ± 18%) than with finasteride (−44 ± 13%; P &lt; 0.01) and a greater decrease was seen with flutamide (−58 ± 18%) than with finasteride (−44 ± 13%; P &lt; 0.05). Flutamide is the fastest in decreasing hair diameter; EE-CPA is the fastest in slowing down hair growth, even though at the end of the treatment there was a significant difference between flutamide and finasteride only (−41 ± 18% vs.− 27 ± 14%; P &lt; 0.05).Flutamide, ketoconazole, and EE-CPA induced a significant decrease in total and free testosterone, 5α-dihydrotestosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione plasma levels. During the EE-CPA treatment, gonadotropins were suppressed, and the sex hormone-binding globulin level increased. Finasteride induced a decrease in dehydroepiandrosterone sulfate and 5α-dihydrotestosterone and an increase in testosterone levels.Very few side-effects were observed during treatment with low doses of flutamide, EE-CPA, and particularly finasteride. Flutamide induced a decrease whereas EE-CPA induced an increase in triglycerides and cholesterol, showing higher values within the normal range. Ketoconazole induced several side-effects and complications, and several people dropped out of the study.Despite different modalities of action and significantly different effects on androgen levels, low doses of flutamide, finasteride, and EE-CPA constitute very satisfactory alternative therapeutic regimens in the treatment of hirsutism.
Restoration of Reproductive Potential by Lifestyle Modification in Obese Polycystic Ovary Syndrome: Role of Insulin Sensitivity and Luteinizing Hormone1
Authors: Huber-Buchholz M.-M. , Carey D. G. P. , Norman R. J. 
Published: January 2014

Weight reduction and exercise have been shown to help with menstrual disturbance and infertility in obese women with polycystic ovary syndrome. We studied the relationship between insulin sensitivity and ovulation patterns in 18 infertile anovulatory obese polycystic ovary syndrome (PCOS) women (NO) with normal glucose tolerance, aged between 22–39 yr with a body mass index of 27–45 kg/m2, before and after a 6-month diet and exercise program. This program promotes healthy lifestyle factors, but does not lead to rapid weight loss. The anthropometric, metabolic, and endocrine factors of these subjects were compared to those of 10 age- and weight-matched PCOS women with regular monthly ovulation (RO).
Before lifestyle modification, the anovulatory subjects had greater central obesity than regular ovulators, as assessed by percent central fat (NO, 45.7 ± 0.8%; RO, 42.2 ± 1.6%; P &lt; 0.05), higher glucose increment after glucose challenge (NO, 10.1 ± 1.0 mmol/L; RO, 6.4 ± 1.1 mmol/L; P &lt; 0.02), lower insulin sensitivity index (NO, 1.2 ± 0.2; RO, 2.8 ± 0.6 μmol/kg·min/pmol/L; P &lt; 0.005), higher plasma LH (NO, 8.9 ± 0.9; RO, 4.6 ± 0.9 IU/L; P &lt; 0.005), and lower plasma sex hormone-binding globulin (NO, 18.0 ± 2.5; RO, 27.8 ± 5.7 nmol/L; P &lt; 0.05].
Anovulatory subjects were classified as responders (R) to the intervention if they regained ovulation during the study. As a result of intervention, R showed an 11% reduction in central fat, a 71% improvement in insulin sensitivity index, a 33% fall in fasting insulin levels, and a 39% reduction in LH levels. None of these parameters changed significantly in nonresponders (NR). At the end of the study, R had lower fasting insulin (R, 13.6 ± 1.7; NR, 23.0 ± 3.5 mU/L) and LH levels (R,5.0 ± 1.7; NR, 7.4± 1.4 IU/L), but similar androgen levels compared to NR.
We conclude that lifestyle modification without rapid weight loss leads to a reduction of central fat and improved insulin sensitivity, which restores ovulation in overweight infertile women with PCOS. Lifestyle modification is the best initial management for obese women seeking to improve their reproductive function.
Serum Levels of Insulin-Like Growth Factor I in 152 Patients with Growth Hormone Deficiency, Aged 19–82 Years, in Relation to Those in Healthy Subjects1
Authors: Hilding Agneta , Hall Kerstin , Wivall-Helleryd Inga-Lena , Sääf Maria , Melin Anna-Lisa , Thorén Marja 
Published: January 2014

Serum insulin-like growth factor I (IGF-I) levels within normal range for age have been reported to be common in adults with GH deficiency (GHD). Therefore, serum IGF-I levels were determined in 152 consecutive patients (71 women and 81 men) with evidence of hypothalamic-pituitary disorders or previous cranial radiation, who fulfilled the presently used criteria for GHD i.e. peak GH response below 3μ g/L at stimulation test. Patients treated for acromegaly were excluded. Forty-three patients, aged 19–63 yr, had childhood onset GHD, and 109, aged 23–82 yr, had adult-onset GHD. Their IGF-I levels were expressed in sd scores in relation to normal reference values based on 448 healthy subjects, aged 20–96 yr (247 women and 201 men). In healthy subjects a linear inverse correlation, without gender difference, was found between logarithmic transformed IGF-I levels and age (r = −0.774; P &lt; 0.001). In contrast, no age dependency was found in GHD patients. All patients with childhood-onset GHD had IGF-I values below −2 sd, significantly lower than those in adult-onset GHD patients (−6.2± 0.3 vs. −3.2 ± 0.2 sd score; P &lt; 0.001). In patients with adult-onset GHD, 34% of the IGF-I levels were within normal range, increasing to 40% in the subgroup above 60 yr of age, in whom 86% were diagnosed with hypothalamic-pituitary tumors. Normal IGF-I was more common in men than in women, but no difference was observed between patients with panhypopituitarism and those with partial pituitary insufficiency. High frequencies of IGF-I levels within the normal range were found in GHD patients with pituitary tumors (20 of 57 nonsecreting pituitary adenomas, 5 of 15 prolactinomas, 6 of 12 Cushing’s disease, and 4 of 25 craniopharyngiomas), but in only 2 of 43 patients with GHD due to other causes.
In conclusion, an IGF-I level below −2 sd seems to be of diagnostic value in GHD with onset in childhood or early adulthood, whereas values within normal range are common in patients over 60 yr of age, especially those with pituitary tumors. The outcome of GH replacement therapy may reveal whether the addition of IGF-I as a diagnostic criterion is of predictive value in older patients.
Gonadotropins, Prolactin, Inhibin A, Inhibin B, and Activin A in Human Fetal Serum from Midpregnancy and Term Pregnancy
Authors: Debieve F. , Beerlandt S. , Hubinont C. , Thomas K. 
Published: January 2014

Using specific enzyme-linked immunosorbent assays we measured inhibin A, inhibin B, and activin A in relation to LH, FSH, and PRL in normal human fetal midpregnancy serum obtained by in utero cord venipuncture (n = 25) and compared these results to those in fetal serum from term pregnancies (n = 23). We also tested serum from fetuses with intrauterine growth retardation (n = 6) or trisomy 21 (n = 6). We found no measurable inhibin A, except in three midpregnancy males (3 of 14). Inhibin B, however, was detected in midpregnancy male fetuses (167 ± 67 pg/mL) and was higher than that in females (16 ± 12 pg/mL). It was present in male term fetuses (125 ± 32 pg/mL), but not in females. The activin A levels did not significantly differ between term and midpregnancy males and females.
LH and FSH were detected in midpregnancy male fetuses (4.4 ± 3.3 and 0.77 ± 0.49 mIU/mL, respectively), with higher levels in females (33.0 ± 23.2 and 54.4 ± 27.7 mIU/mL, respectively), and were suppressed at term. PRL did not exhibit sexual difference, but showed a higher level at term (322.4 ± 113.8 ng/mL) than at midpregnancy (33.0 ± 26.1 ng/mL). Comparison of inhibin B with FSH levels showed correlation coefficients of −0.565 at midpregnancy vs. +0.445 at term. Serum from fetuses with intrauterine growth retardation or trisomy 21 did not show any different hormonal profiles.
These data suggest that inhibin B is probably an additional factor in FSH inhibition at midpregnancy, whereas activin A is not associated with any change in the different studied populations. We speculate that inhibin A could be a method to detect maternal blood contamination in cord venipuncture.
The Effects of Hormone Replacement Therapy and Raloxifene on C-Reactive Protein and Homocysteine in Healthy Postmenopausal Women: A Randomized, Controlled Trial1
Authors: Walsh Brian W. , Paul Sofia , Wild Robert A. , Dean Robert A. , Tracy Russell P. , Cox David A. , Anderson Pamela W. 
Published: January 2014

C-Reactive protein and homocysteine are independent risk factors for the development of cardiovascular disease. This study compared the effects of hormone replacement therapy (HRT) and raloxifene on serum C-reactive protein and homocysteine levels as markers of cardiovascular risk in healthy postmenopausal women. Healthy postmenopausal women (n = 390) were enrolled in a double blind, randomized, placebo-controlled, 6-month trial at eight out-patient sites in the United States. Women were randomly assigned to receive continuous combined HRT (0.625 mg/day conjugated equine estrogen and 2.5 mg/day medroxyprogesterone acetate), raloxifene (60 or 120 mg/day), or placebo for 6 months. C-Reactive protein and homocysteine were measured in baseline and 6-month serum samples. HRT increased C-reactive protein levels by 84% (P &lt; 0.001), whereas raloxifene (60 and 120 mg/day) had no significant effect (−6% and −4%, respectively; P &gt; 0.2). Raloxifene (60 and 120 mg/day) significantly lowered serum levels of homocysteine by 8% (P = 0.014) and 6% (P = 0.024), respectively, similar to the 7% (P = 0.014) reduction obtained with HRT.We conclude that HRT and raloxifene lower serum homocysteine levels to a comparable extent in postmenopausal women. Whereas cardiovascular risk predicted by C-reactive protein in healthy postmenopausal women is not influenced by raloxifene, the relationship between elevated C-reactive protein levels with HRT and cardiovascular disease events requires further study.
Energy Economy Hampers Body Weight Loss after Gastric Bypass
Authors: Bobbioni-Harsch E. , Morel P. , Huber O. , Assimacopoulos-Jeannet F. , Chassot G. , Lehmann T. , Volery M. , Golay A. 
Published: January 2014

The impact of energy economy on body weight loss was investigated in 20 obese women, submitted to Roux-en-Y gastric bypass. Resting energy expenditure (REE), substrate oxidation rates, plasma glucose, free fatty acid, and insulin and leptin levels were measured before and 3, 6, and 12 months after surgery. Predicted REE was obtained from linear regression analysis of REE and fat free mass, in a group of 85 women, whose body mass index ranged between 20 and 60 kg/m2. The deviation from predicted REE, calculated as area under the curve (AUC) over the 12-month period for each patient, was considered as the expression of energy economy. Energy economy AUC was significantly (P &lt; 0.005) negatively related to the weight lost during 12 months after surgery.Energy intake, calculated from self-reported food consumption, was also expressed as AUC. Energy intake AUC showed a significant (P &lt; 0.002) positive correlation with weight loss.Lipid oxidation rate, also calculated as AUC, significantly correlated, negatively, with energy economy (P &lt; 0.001) and, positively, with energy intake (P &lt; 0.002). Preoperative leptin values were significantly (P &lt; 0.01) linked to individual energy economy capacity.In conclusion, after Roux-en-Y gastric bypass, energy economy hampers the weight loss process, probably through a low fat oxidation rate.
Detection of Minimal Levels of Serum Anti-Müllerian Hormone during Follow-Up of Patients with Ovarian Granulosa Cell Tumor by Means of a Highly Sensitive Enzyme-Linked Immunosorbent Assay
Authors: Long Wen-Qing , Ranchin Valérie , Pautier Patricia , Belville Corinne , Denizot Philippe , Cailla Hélène , Lhommé Catherine , Picard Jean-Yves , Bidart Jean-Michel , Rey Rodolfo 
Published: January 2014

Granulosa cell tumors (GCT) are ovarian neoplasms that tend to recur and spread in the pelvis and the abdomen several years after the initial treatment. Anti-Müllerian hormone (AMH) is a reliable serum marker of these tumors. To enhance the availability and the sensitivity of serum AMH determination, we developed an ultrasensitive enzyme-linked immunosorbent assay. In this work we compare the results of serum AMH levels, obtained using the ultrasensitive and the traditional assays, in 31 patients with ovarian GCT followed up for up to 7 yr.The ultrasensitive enzyme-linked immunosorbent assay has a significantly higher sensitivity than the traditional one. This resulted in the detection of low serum AMH levels, which were undetectable with the traditional assay, in several cases including one patient in whom a recurrence of a GCT had developed and two patients in whom the treatment had not been completely successful. These cases highlight the importance of the availability of a highly sensitive assay allowing evaluation with high precision of the results of treatment and to detect the recurrences of GCT at an early, preclinical stage.
Predicting Phenotype in Steroid 21-Hydroxylase Deficiency? Comprehensive Genotyping in 155 Unrelated, Well Defined Patients from Southern Germany
Authors: Krone Nils , Braun Andreas , Roscher Adelbert Anton , Knorr Dietrich , Schwarz Hans Peter 
Published: January 2014

AbstractCongenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders. CAH is most often caused by deficiency of steroid 21-hydroxylase. The frequency of CYP21-inactivating mutations and the genotype-phenotype relationship were characterized in 155 well defined unrelated CAH patients. We were able to elucidate 306 of 310 disease-causing alleles (diagnostic sensitivity, 98.7%). The most frequent mutation was the intron 2 splice site mutation (30.3%), followed by gene deletions (20.3%), the I172N mutation (19.7%) and large gene conversions (7.1%). Five point mutations were detected that have not been described in other CAH cohorts. Genotypes were categorized in 4 mutation groups (null, A, B, and C) according to their predicted functional consequences and compared to the clinical phenotype. The positive predictive value for null mutations (ppvnull) was 100%, as all patients with these mutations had a salt-wasting phenotype. In mutation group A (intron 2 splice site mutation in homozygous or heterozygous form with a null mutation), the ppvA to manifest with salt-wasting CAH was 90%. In group B predicted to result in simple virilizing CAH (I172N in homozygous or compound heterozygous form with a more severe mutation), ppvB was 74%. In group C (P30L, V281L, P453S in homozygous or compound heterozygous form with a more severe mutation), ppvC was 64.7% to exhibit the nonclassical form of CAH, but 90% when excluding the P30L mutation. Thus, in general, a good genotype-phenotype relationship is shown in patients with either the severest or the mildest mutations. A considerable degree of divergence is observed within mutation groups of intermediate severity. As yet undefined factors modifying 21-hydroxylase gene expression and steroid hormone action are likely to account for these differences in phenotypic expression.
Gender Difference in Insulin-Like Growth Factor I Response to Growth Hormone (GH) Treatment in GH-Deficient Adults: Role of Sex Hormone Replacement
Authors: Span J. P. T. , Pieters G. F. F. M. , Sweep C. G. J. , Hermus A. R. M. M. , Smals A. G. H. 
Published: January 2014

Abstract
GH production in healthy women is about thrice that in men. Yet insulin-like growth factor I (IGF-I) levels are similar, suggesting a lower responsivity to GH in women. In untreated GH-deficient adults, basal IGF-I levels are reportedly lower in females than in males, and the therapeutic recombinant human GH (rhGH) dose required to achieve optimal IGF-I levels is higher in the former, suggesting a pivotal role of estrogens on rhGH requirement in GH-deficient patients. We, therefore, analyzed our 2-yr data on the effect of rhGH on serum IGF-I in 77 GH-deficient patients (33 men, mean ± sd age, 37.2 ± 13.8 yr; 44 women, mean ± sd age, 36.9 ± 11.9 yr) with due attention to gender differences and to the effects of sex hormone replacement. Of the 44 women, 33 had estrogen substitution. Of the 33 men, 23 were on androgen replacement. Patients (11 premenopausal women and 10 men) not on hormonal replacement were eugonadal.
Basal IGF-I levels in untreated GH-deficient women were significantly lower than in men (8.8 ± 0.7 nmol/L vs. 12.2 ± 0.9 nmol/L; P &lt; 0.01), despite similar basal GH levels. The daily rhGH dose per kg body weight required to normalize IGF-I in women was higher than in men, the difference being statistically significant at all time points (P &lt; 0.05–0.01). The IGF-I increase (Δ) per IU GH/day·kg over the 24-month period was about twice higher in men than in women. Also calculated on a weight basis, rhGH responsivity (rhGH responsivity = (ΔIGF1(nmol/L)/dose (IU/day/kg)) was higher in men than in women at all time intervals (P &lt; 0.05–0.01).
Estrogen replacement in women significantly increased rhGH requirement. The rhGH dose per kg body weight required in estrogen-substituted women was significantly higher than in nonestrogen-substituted women (P &lt; 0.01 at t = 18 and 24 months, respectively). In women on estrogen substitution, rhGH responsivity plateaued from 6 months on, whereas in eugonadal women without estrogen substitution the responsivity for rhGH increased over time. In men, the reverse was true; rhGH responsivity increased over time in men on androgen substitution, but plateaued in men without androgen substitution.
The mechanisms underlying this gender difference are not known. Differential influences of estrogens and androgens on the expression of the GH receptor gene and IGF-I messenger RNA may be operative.
The present study confirms short-term data published in the literature on a sex difference in rhGH dose requirement in GH-deficient patients. It furthers extends the data by demonstrating that this sex difference in GH responsivity persists and changes during the 24 months of the study. Moreover, it shows that estrogen replacement blunts the IGF-I response to rhGH in women, whereas in men with androgen substitution the responsivity increases over time, thus bearing a risk of undertreatment in women and overtreatment in men.
Withdrawal of Long-Term Physiological Growth Hormone (GH) Administration: Differential Effects on Bone Density and Body Composition in Men with Adult-Onset GH Deficiency*
Authors: Biller Beverly M. K. , Sesmilo Gemma , Baum Howard B. A. , Hayden Douglas , Schoenfeld David , Klibanski Anne 
Published: January 2014

Abstract
Adults with acquired GH deficiency (GHD) have been shown to have osteopenia associated with a 3-fold increase in fracture risk and exhibit increased body fat and decreased lean mass. Replacement of GH results in decreased fat mass, increased lean mass, and increased bone mineral density (BMD). The possible differential effect of withdrawal of GH replacement on body composition compartments and regional bone mass is not known. We performed a randomized, single blind, placebo-controlled 36-month cross-over study of GH vs. placebo (PL) in adults with GHD and now report the effect of withdrawal of GH on percent body fat, lean mass, and bone density, as measured by dual energy x-ray absorptiometry. Forty men (median age, 51 yr; range, 24–64 yr) with pituitary disease and peak serum GH levels under 5μ g/L in response to two pharmacological stimuli were randomized to GH therapy (starting dose, 10 μg/kg·day, final dose 4 μg/kg·day) vs. PL for 18 months. Replacement was provided in a physiological range by adjusting GH doses according to serum insulin-like growth factor I levels. After discontinuation of GH, body fat increased significantly (mean ± sem, 3.18 ± 0.44%; P = 0.0001) and returned to baseline. Lean mass decreased significantly (mean loss, 2133 ± 539 g; P = 0.0016), but remained slightly higher (1276 ± 502 g above baseline;P = 0.0258) than at study initiation.
In contrast to the effect on body composition, BMD did not reverse toward pretreatment baseline after discontinuation of GH. Bone density at the hip continued to rise during PL administration, showing a significant increase (0.0014 ± 0.00042, g/cm2·month; P = 0.005) between months 18–36. Every bone site except two (radial BMD and total bone mineral content), including those without a significant increase in BMD during the 18 months of GH administration, showed a net increase over the entire 36 months. Therefore, there is a critical differential response of the duration of GH action on different body composition compartments. Physiological GH administration has a persistent effect on bone mass 18 months after discontinuation of GH.