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1.
Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels.
Panidis, D, Farmakiotis, D, Rousso, D, Kourtis, A, Katsikis, I, Krassas, G
Fertility and sterility. 2008;(4):899-906
Abstract
OBJECTIVE To investigate the combined effect of diet and orlistat, for 24 weeks, on anthropometric features, hormonal parameters, and indices of insulin resistance in obese women with polycystic ovary syndrome (PCOS) and in obese women without the syndrome. DESIGN Prospective clinical study. SETTING Department of obstetrics and gynecology in a major university in Greece. PATIENT(S): Eighteen selected women with PCOS were matched for age and body mass index with 14 obese control women. INTERVENTION(S): Subjects were prescribed an energy-restricted diet, and orlistat (120 mg, 3 times per d) was administered to all subjects for 24 weeks. MAIN OUTCOME MEASURE(S): At baseline, week 12, and week 24, after an overnight fast, blood samples were collected, and serum levels of FSH, LH, PRL, T, Delta(4)A, DHEAS, 17 alpha-hydroxyprogesterone, sex hormone-binding globulin, glucose, and insulin were measured. RESULT(S): Testosterone levels were significantly decreased with treatment in women with PCOS; this decrease was attributed to the first trimester, whereas T levels did not change during the second 12-week period. In women with PCOS, insulin levels and HOMA-IR values were decreased during the first 12 weeks, whereas no significant change was observed during the second trimester. CONCLUSION(S): Orlistat administration, combined with diet, for 24 weeks, resulted in significant weight loss and improvement of insulin resistance in obese women, with or without PCOS. Moreover, T levels were significantly decreased in women with PCOS. There appears to be a trend during the first 12-week period for greater improvement of metabolic and hormonal parameters in women with PCOS.
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2.
[Safety of long-term replacement hormonal therapy in patients with erectile dysfunction and androgen deficiency].
Morgunov, LIu, Vertkin, AL, Pushkar', DIu
Urologiia (Moscow, Russia : 1999). 2007;(5):49-51
Abstract
Safety of testosterone undecanoate in relation to initiation of cancer and prostatic adenoma (PA) in patients with androgenic deficiency and erectile dysfunction (ED) was studied for 12 months in 49 patients aged 57 to 73 years treated with intramuscular testosteron injections. The size of the prostate in patients with adenoma was 46.34 +/- 21.12 cm3 while in adenoma-free patients--19.11 +/- 6.57 sm3. Diabetes mellitus of type 2 (DM-2) was diagnosed in 46.9% patients. All the patients had documented hypogonadism and ED. Tests for PSA and transrectal ultrasound investigation was made in all the patients. 12 month testosterone therapy produced normalization of a mean level of testosterone in both groups, index of erectile function increased. In one patient PSA rose higher than normal value. None of the patients developed obstruction of the urinary tract. Body mass index, lipid spectrum and carbohydrate metabolism also improved. Thus, long-term therapy with testosterone undecanoate has no effect on PSA level, does not induce urinary obstruction with enlarged prostate. The presence of DM-2 is not a contraindication for androgen therapy in adenoma patients. By reducing body mass index, total cholesterol, triglycerides and LDLP, testosterone therapy lowers the risk of prostatic cancer.
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3.
Elevated plasma concentration of asymmetric dimethylarginine that is reduced by single dose testosterone administration in idiopathic hypogonadotropic hypogonadism patients.
Cakir, E, Ozcan, O, Yaman, H, Akgul, EO, Bilgi, C, Erbil, MK, Yesilova, Z
The Journal of clinical endocrinology and metabolism. 2005;(3):1651-4
Abstract
Our aim was to investigate whether plasma l-arginine and asymmetric dimethylarginine (ADMA) concentrations and nitric oxide (NO) production are altered in male idiopathic hypogonadotropic hypogonadism (IHH) patients in the hypogonadal state and after single dose testosterone administration compared with those in control subjects. Eighteen newly diagnosed male patients with IHH and 20 healthy volunteer controls matched by age and body mass index were enrolled in the study. Single dose testosterone was administrated im. Initially, pretreatment blood samples were collected after overnight fasting. Posttreatment blood samples were drawn 10 d after the injection. ADMA, l-arginine, and NO were measured in pre- and posttreatment blood samples. The pretreatment ADMA and l-arginine levels were significantly higher, and plasma nitrite plus nitrate (NOx) levels were lower than those in the control group. After 10 d of treatment, ADMA and l-arginine levels were significantly reduced, and NOx levels were significantly increased. There was a significant positive correlation (P < 0.01) between ADMA and l-arginine and a negative correlation between ADMA and NOx levels in patients and controls. In conclusion, the patients with IHH showed elevated plasma ADMA levels associated with a reduction in NO production. Single dose parenteral T administration lowered ADMA concentrations and increased NO production to the control group values.
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4.
Effects of oral administration of androstenedione on plasma androgens in young women using hormonal contraception.
Bassindale, T, Cowan, DA, Dale, S, Hutt, AJ, Leeds, AR, Wheeler, MJ, Kicman, AT
The Journal of clinical endocrinology and metabolism. 2004;(12):6030-8
Abstract
Androstenedione as a dietary supplement has been targeted at the sporting community, but there are limited data regarding its effects on plasma androgens in young women. A double-blind, cross-over study was undertaken involving 10 women (20-32 yr) using hormonal contraception. Because contamination of supplements has been reported, an in-house oral formulation was prepared containing purified androstenedione, the control being lactose only. After oral administration of a single dose of androstenedione (100 mg), blood was collected frequently up to 8 h and at 24 h. Maximum plasma androgen concentrations observed between volunteers were well above the upper limit of reference ranges for women, being 121-346 nmol/liter for androstenedione, 14-54 nmol/liter for testosterone (T), 11-32 nmol/liter for 5alpha-dihydrotestosterone, and 23-90 nmol/liter for 3alpha-androstanediol glucuronide. The free androgen index and T concentration changed in a similar manner. The mean change in area under the plasma concentration-time curve (0-24 h), compared with control data were: androstenedione approximately 7-fold, T approximately 16-fold, 5alpha-dihydrotestosterone approximately 9-fold, and 3alpha-androstanediol glucuronide approximately 5-fold; the mean conversion ratio of androstenedione to T was 12.5% (range 7.8-21.6%). Increases in T area under the plasma concentration-time curve were correlated with SHBG concentration (r = 0.80; P = 0.005). Formulation characteristics and SHBG levels appear to be important factors when considering plasma androgen increases after acute androstenedione administration.
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5.
Serum leptin levels in premature pubarche and prepubertal girls with and without obesity.
Teixeira, RJ, Ginzbarg, D, Rodrigues Freitas, J, Fucks, G, Silva, CM, Bordallo, MA
Journal of pediatric endocrinology & metabolism : JPEM. 2004;(10):1393-8
Abstract
Leptin can be regarded as a marker of the nutritional status of the body. This study was performed to determine the correlation of leptin levels with insulin (I) and androgens in girls with premature pubarche (PP) and prepubertal controls (C) with (OB) or without (nOB) obesity. We studied 25 girls with PP and 14 C; girls were dived into two subgroups according to body mass index (BMI): OB (18 PP and 8 C) and nOB (7 PP and 6 C). Obesity was defined as BMI >95th percentile for chronological age. Serum levels of leptin, I, glucose (G), DHEAS, testosterone, androstenedione (A), cortisol, SHBG, IGFBP-1 and lipid profile were measured. The fasting G to I ratio (FGIR) was calculated and FGIR <7 was considered as suggestive of I resistance (IR). Data were analyzed comparing PP vs C and OB vs nOB. Serum DHEAS (0.60 +/- 0.45 vs 0.18 +/- 0.22 microg/ml) and A (895.5 +/- 420.4 vs 457.0 +/- 352.1 pg/ml) levels were significantly higher in PP than C. Other hormonal and metabolic parameters were similar. Serum leptin (30.8 +/- 18.3 vs 8.1 +/- 5.9 ng/ml), A (841.8 +/- 471.1 vs 522.5 +/- 317.2 pg/ml), DHEAS (0.53 +/- 0.44 vs 0.31 +/- 0.39 microg/ml), G (88.4 +/- 8.8 vs 80.2 +/- 8.1 mg/dl), I (13.5 +/- 7.7 vs 5.1 +/- 3.7 microU/ml) and total cholesterol (TC) (180.5 +/- 30.9 vs 161.8 +/- 29.5 mg/dl) levels were greater in the OB than in the nOB group. IR was observed in 10 girls with OB and in one with nOB. Leptin was correlated with BMI (r = 0.83), SHBG (r = -0.44), IGFBP-1 (r = -0.47), I (r = 0.37), A (r = 0.48) and TC (r = 0.36), but in multiple regression analysis only with BMI (r2 = 0.72, p < 0.001). Girls with PP and prepubertal OB girls showed elevated leptin levels independent of I and androgen levels. Girls with OB had a greater degree of hyperandrogenism and IR. As obesity, IR and hyperandrogenism are common findings in polycystic ovary syndrome (PCOS), which is more prevalent in young women with a history of PP, a role of leptin in PCOS can be suggested. In addition, girls with PP could be considered a population at risk for plurimetabolic syndrome.
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6.
Urinary profile of androgen metabolites in a population of sportswomen during the menstrual cycle.
Bricout, VA, Wright, F, Lagoguey, M
International journal of sports medicine. 2003;(3):197-202
Abstract
The aim of this investigation was to evaluate the urinary profile of androgen metabolites during menstrual cycle in both young-trained female athletes, and young sedentary women, not presenting any pathological signs. Urines were collected for 24 hours (08 : 00 a. m. the first day to 08 : 00 a. m. the second day) from all sportive and sedentary subjects. All steroids were measured by specific radioimmunological analysis, and the implications of these results in terms of concentrations and modifications by exercise will be discussed. During follicular phase, control values were respectively, testosterone glucuronide (TG): 1.67 +/- 0.70 nmol x mmol C -1; epitestosterone glucuronide (ETG): 2.51 +/- 0.88 nmol x mmol C -1; TG/ETG ratio: 0.72 +/- 0.26 and cortisol (FLU): 10.02 +/- 0.79 nmol x mmol C -1. No significant modifications were observed during luteal phase (respectively: TG: 1.48 +/- 0.50 nmol x mmol C -1; ETG: 2.65 +/- 0.93 nmol x mmol C -1; TG/ETG ratio: 0.67 +/- 0.31 and FLU: 9.29 +/- 3.37 nmol x mmol C -1. Similarly, no significant effect of physical training was observed on studied parameters between these two groups during either follicular phase (TG: 1.96 +/- 1.00 nmol x mmol C -1; ETG: 1.97 +/- 0.70 nmol x mmol C -1; TG/ETG ratio: 0.66 +/- 0.05 and FLU: 11.31 +/- 3.73 nmol x mmol C -1) or luteal phase (TG: 1.93 +/- 0.86 nmol x mmol C -1; ETG: 3.19 +/- 1.23 nmol x mmol C -1; TG/ETG ratio: 0.69 +/- 0.33 and FLU: 9.52 +/- 3.86 nmol x mmol C -1). It is concluded that although physical training could play a role in androgen metabolism, it has no significant incidence on urinary TG/ETG ratio. This study thus confirms that sportswomen can also be considered as normal subjects when they do not present any obvious endocrine disorder induced by physical activity.
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7.
Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids.
Genazzani, AD, Stomati, M, Bernardi, F, Pieri, M, Rovati, L, Genazzani, AR
Fertility and sterility. 2003;(6):1495-501
Abstract
OBJECTIVE To evaluate the effects of a low-dose DHEA supplementation on hormonal parameters in early and late postmenopausal women. DESIGN Prospective case study. SETTING Postmenopausal women in a clinical research environment. PATIENT(S): Twenty postmenopausal women were divided in two groups according to age (50-55 and 60-65 years). INTERVENTION(S): All patients underwent hormonal evaluation before and at 3, 6, 9, and 12 months of therapy (25 mg/d of DHEA orally). Pelvic ultrasound examination and Kupperman score were performed before and after 3, 6, and 12 months of therapy. MAIN OUTCOME MEASURE(S): Plasma DHEA, DHEAS, estrone (E1), E2, P, androstenedione (A), T, dihydrotestosterone, 17alpha-hydroxyprogesterone (17-OHP), cortisol (F), allopregnanolone, beta-endorphin, sexual hormone-binding globulin (SHBG), LH, FSH, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) concentrations. RESULT(S): The levels of all the steroids that derive from DHEA metabolism increased in plasma with DHEA administration. Also neurosteroids (namely allopregnanolone) and endorphin showed increased plasma levels, whereas both gonadotropins were significantly reduced. Endometrial thickness did not change throughout the study period. CONCLUSION(S): Administration of low doses (25 mg) of DHEA positively modulates several endocrine parameters in early and late postmenopausal women, inducing the increase of the androgenic, estrogenic, and progestogenic milieu and reducing the climateric symptoms, similarly to estroprogestin replacement therapy. These data suggest that DHEA supplementation is a more effective replacement therapy than a simple "dietary supplement."
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8.
Effects of androgen manipulation on postprandial triglyceridaemia, low-density lipoprotein particle size and lipoprotein(a) in men.
Hislop, MS, St Clair Gibson, A, Lambert, MI, Noakes, TD, Marais, AD
Atherosclerosis. 2001;(2):425-32
Abstract
Although androgenic hormones decrease HDLC concentration, no direct evidence has linked them to atherosclerosis. The present study was undertaken to extend our ability to assess risk associated with androgen induced lipoprotein(Lp) changes by simultaneously gathering information about postprandial triglyceridaemia (PPT), LDL particle size, HDL and Lp(a) in men either taking exogenous androgens or with suppressed endogenous androgen concentrations. The experimental groups comprised nine male bodybuilders who self-administered anabolic-androgenic steroids (AAS) for a mean period of 6.5 weeks, and 10 healthy men whose testosterone concentration had been reversibly suppressed for 5 weeks using the GnRH agonist triptorelin (Decapeptyl; D-Trp-6-LHRH). A separate group receiving no hormonal treatment provided analytical control (n=7). Lipoprotein size was assessed by gradient gel electrophoresis categorisation (GGE), lipoprotein concentrations by immuno and enzymatic assays and PPT by a standardised oral fat tolerance test (65g /m(2)). Testosterone concentration was significantly reduced on triptorelin from 7.32+/-1.92 to 1.15+/-0.57 ng/ml (P=0.002). High dose AAS use was confirmed by urinalysis. With AAS use, mean HDLC and Lp(a) concentrations and PPT decreased from 0.9+/-0.3 to 0.7+/-0.3 mmol/l (P=0.004), 125+/-128 to 69+/-73 U/l (P=0.008) and 11.6+/-10.0 mmol/l h to 7.5+/-5.4 mmol/l h (P=0.027) respectively. Mean total cholesterol and LDLC were unchanged. LDL size was unchanged in six AAS users, decreased in one but remaining in the normal size range, and increased in two from small LDL to the normal range. Size changes in the latter two subjects were associated with 42 and 58% reductions in PPT respectively. In the triptorelin group, mean total cholesterol, HDLC and Lp(a) were increased from 4.8+/-0.8 mmol/l to 5.2+/-1.0 mmol/l (P=0.039), 1.1+/-0.2 to 1.4+/-0.3 mmol/l (P=0.002) and 278+/-149 to 377+/-222 U/l (P=0.004) respectively. Mean LDLC concentration and PPT were unchanged. LDL particle size increased in four, decreased in two, and was unchanged in four subjects. LDL size decreased in two and showed no change in the other five control subjects. Other lipid measures were unchanged in the control group. Thus, apart from lowering HDLC concentrations, no other potentially atherogenic effects of endogenous androgens or AAS were observed. A suppression of Lp(a) as well as a reduced PPT and increased LDL size in predisposed individuals may be antiatherogenic effects of AAS.