c-peptide and Hyperandrogenism

A total of 12 women (24.2 +/- 1.6 years old, BMI 36.7 +/- 1.5 Kg/m2) with hyperandrogenism (HA) and with normal glucose tolerance test were studied to evaluate the involvement of endogenous opioids in the pathophysiology of insulin secretion and insulin sensitivity in HA by administering naltrexone, an oral opioid receptor antagonist. Six patients received naltrexone orally (75 mg daily) and another six received placebo for 12 weeks (double-blind study). Before and after therapy a frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed. The insulin sensitivity index (SI) was determined by Bergman's program. SHBG, DHEAS, testosterone, free androgen index (FAI) and plasma concentrations of IGF-I and IGFBP-1 were determined in 3 basal samples, before and after therapy. Treatment with naltrexone in hyperandrogenic patients resulted in a decrease in fasting insulin concentrations of 40% and C-peptide concentrations of 50% (p < 0.05). Insulin and C-peptide from the FSIVGTT displayed a similar pattern with a fall in the area under the curve under naltrexone treatment of 34% for insulin and 35% for C-peptide. Insulin sensitivity did not change under naltrexone (1.26 +/- 0.19 vs 1.32 +/- 0.32 10(-4) x min(-1)/(uU/ml)) or placebo (0.95 +/- 0.19 vs 1.12 +/- 0.28 10(-4) x min(-1)/(uU/ml)) administration. However, glucose effectiveness increased significantly with naltrexone (2.231 +/- 0.002 vs 3.354 +/- 0.006 x 10(-2) min(-1)). Glucose (fasting and area under the curve) was not modified significantly after naltrexone administration. Baseline hormone levels were similar in the two groups, and they did not change after long-term treatment with naltrexone or placebo. In conclusion, these results support the hypothesis of elevated opioid tonus and increased insulin secretion as a possible mechanism of hyperinsulinism in a group of hyperandrogenic women of ovarian origin. This alteration could act as an additional factor in the pathogenesis of insulin resistance found in an important proportion of these patients.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Dehydroepiandrosterone Sulfate; Double-Blind Method; Female; Glucose Tolerance Test; Humans; Hyperandrogenism; Insulin; Insulin Secretion; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Naltrexone; Narcotic Antagonists; Opioid Peptides; Placebos; Testosterone

Acne beyond 25 years of age is frequently associated with hormonal derangement in women. Hormonal association provides the impetus for hormonal therapy as well as underpins the need for blood investigations in this population. Hence, we aim to estimate the presence of hormonal derangement and lipid alteration in female adult acne.. A prospective, observational study was conducted in Dhulikhel Hospital from July 2015 to February 2016. Females older than 25 years with acne were taken in the study after informed consent. Total 100 patients were enrolled after sample size estimation. Hormonal paneland lipid profile were measured. Hormones tested were androgens, C-peptide and thyroid stimulating hormone.Data analysis was done with SPSS-23. Bivariate analysis was done by chi-square test for categorical data.. In this study, majority of patients were younger than 30 years (70.5%) and perioral area most commonly involved. Hormonal alteration was seen in 37.2% patients, among which17.9% had hyperandrogenism, 15.4% had abnormal thyroid level and 10.3% had high C-peptides respectively. Lipid profile was altered in 15.4% patients. Hormonal alteration had significant association with irregular menstruation (P<0.05) but not acne severity.. We observed hormonal alteration frequently in females with adult acne, which comprised of various hormonal parameters including hyperandrogenism.Hormonal alteration reflects deranged metabolic milieu and we suggest that wide hormonal panel should be done in female adult acne. Relationship of hormones with menstrual irregularity but not with acne severity, suggest that clinical symptoms should lead hormonal investigations in all grades of acne.

Topics: Acne Vulgaris; Adult; Androgens; C-Peptide; Female; Humans; Hyperandrogenism; Lipids; Middle Aged; Nepal; Prospective Studies; Severity of Illness Index; Tertiary Care Centers; Thyrotropin

Elevated testosterone levels during prenatal life lead to hyperandrogenism and insulin resistance in adult females. This study evaluated whether prenatal testosterone exposure leads to the development of insulin resistance in adult male rats in order to assess the influence of gonadal hormones on glucose homeostasis in these animals. Male offspring of pregnant rats treated with testosterone propionate or its vehicle (control) were examined. A subset of male offspring was orchiectomized at 7 wk of age and reared to adulthood. At 24 wk of age, fat weights, plasma testosterone, glucose homeostasis, pancreas morphology, and gastrocnemius insulin receptor (IR) beta levels were examined. The pups born to testosterone-treated mothers were smaller at birth and remained smaller through adult life, with levels of fat deposition relatively similar to those in controls. Testosterone exposure during prenatal life induced hyperinsulinemia paralleled by an increased HOMA-IR index in a fasting state and glucose intolerance and exaggerated insulin responses following a glucose tolerance test. Prenatal androgen-exposed males had more circulating testosterone during adult life. Gonadectomy prevented hyperandrogenism, reversed hyperinsulinemia, and attenuated glucose-induced insulin responses but did not alter glucose intolerance in these rats. Prenatal androgen-exposed males had decreased pancreatic islet numbers, size, and beta-cell area along with decreased expression of IR in gastrocnemius muscles. Gonadectomy restored pancreatic islet numbers, size, and beta-cell area but did not normalize IRbeta expression. This study shows that prenatal testosterone exposure leads to a defective pancreas and skeletal muscle function in male offspring. Hyperinsulinemia during adult life is gonad-dependent, but glucose intolerance appears to be independent of postnatal testosterone levels.

Topics: Animals; Blood Glucose; Body Weight; C-Peptide; Female; Glucose Intolerance; Hyperandrogenism; Hyperinsulinism; Insulin-Secreting Cells; Islets of Langerhans; Male; Muscle, Skeletal; Orchiectomy; Pancreas; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Receptor, Insulin; Testosterone; Testosterone Propionate

Hyperandrogenism is the pathological condition, which clinical signs are "androgendependent dermopathies" (seborrhea, acne, hirsutism, alopecia) and not in every cases evidence with hyperandrogenemia. Free testosterone is the most frequent marker of hyperandrogenism, but its determination routinely not feasible in all laboratories. Therefore, some models for calculating free and bioavailable testosterone have been developed. In women the testosterone sources are not only ovaries and adrenal glands, but also abdominal and peripheral fat. There are many investigations to definite correlations between body mass index, androgens and sex hormone binding globulin. The aim of this study was to define the correlations between clinical, biochemical markers of hyperandrogenism and body mass index, with regard of abdominal obesity in young women with hirsutism. 83 female adolescents (14-20 year) with hirsutism and 20 female adolescents in control group were included. C-peptide, estradiol, total testosterone, sex hormone binding globulin (SHBG) were measured. Free androgen index (FAI), free (cFT) and bioavailable (Bio-T) testosterone were calculated. The levels of C-peptide and glucose were used to compute Homa-IR (homeostasis model assessment for insulin resistance). There were detected significant high levels by all hormonal parameters of hyperandrogenism in women with hirsutism, than in control group. In patients with abdominal obesity were also found significant high levels by all calculated parameters of hyperandrogenism and significant low level of steroid-bind globulin, than in patients with central obesity. In two groups by hirsutism degree were not detected any differences between androgen markers. The findigs of this research suggest, that android obesity in female adolescents with hirsutism can cause harder hyperandrogenism and elevate free androgen index, free and bioavailable testosterone levels. The prophylactic reduction of body mass index may prevent complications.

Topics: Adolescent; Adult; Androgens; Blood Glucose; Body Mass Index; C-Peptide; Estradiol; Female; Hirsutism; Humans; Hyperandrogenism; Menarche; Obesity, Abdominal; Prospective Studies; Sex Hormone-Binding Globulin; Testosterone; Young Adult

The exaggerated 17-hydroxyprogesterone response to GnRH agonists, which reflects functional ovarian hyperandrogenism (FOH), is believed to be the prominent abnormality in women with polycystic ovary syndrome (PCOS).. Our objectives were to quantify the prevalence of PCOS with FOH and to evaluate whether the presence of FOH may distinguish different clinical and biochemical phenotypes.. We conducted an observational study at an academic hospital that included 148 PCOS women and 22 healthy age-matched normal-weight control women.. A hormone profile was taken at baseline and in response to (1-24)ACTH and to a GnRH agonist, buserelin, administered during dexamethasone suppression.. Based on the data obtained in the control subjects, the PCOS patients were divided into two groups, one with a normal (NR-PCOS, n = 78) and one with a high 17-hydroxyprogesterone response (HR-PCOS, n = 70) to buserelin. The two groups of PCOS subjects had similar anthropometric parameters and clinical signs of hyperandrogenism. Age and body weight at menarche were significantly lower and higher, respectively, in the HR-PCOS group than the NR-PCOS group. Moreover, the HR-PCOS group had higher basal testosterone (P < 0.001), free androgen index (P < 0.01), 17-hydroxyprogesterone (P < 0.05), estrogens (P < 0.05), area under the curve for insulin (insulin(AUC)) (P < 0.05), and C-peptide(AUC) (P < 0.01) and lower insulin sensitivity (as composite insulin sensitivity index) (P < 0.05) than the NR-PCOS group. The response of 17-hydroxyprogesterone to (1-24)ACTH (as percent variation) was lower in the HR-PCOS group with respect to the NR-PCOS group (P < 0.05), whereas the response of cortisol, androstenedione, and dehydroepiandrosterone was similar. Finally, the HR-PCOS group had lower percent suppression of androstenedione (P < 0.001) and 17-hydoxyprogesterone (P < 0.05) to dexamethasone. In a multiple regression model applied in all PCOS women, insulin(AUC) but not androgens or markers of insulin resistance predicted the 17-hydroxyprogesterone response to buserelin to a highly significant extent (t = 3.269; P < 0.01).. This study indicates that the paradigm that FOH is a specific feature of the PCOS status can no longer be sustained. We have shown that women with an exaggerated 17-hydroxyprogesterone response to a GnRH agonist, buserelin, are characterized by more severe hyperandrogenemia, glucose-stimulated beta-cell insulin secretion, and worse insulin resistance than those without evidence of FOH. Our data may be consistent with the hypothesis that excess insulin may represent a candidate factor responsible for FOH in these women, through the overactivation of the cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17) enzyme pathway.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adult; Anthropometry; Blood Glucose; Buserelin; C-Peptide; Cosyntropin; Dexamethasone; Female; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Hormones; Humans; Hyperandrogenism; Insulin; Middle Aged; Ovarian Diseases; Phenotype; Polycystic Ovary Syndrome; Prospective Studies

To determine whether 3-month GnRH analogue (GnRH-a) administration to hyperandrogenic anovulatory patients and healthy women affects glucose utilization or endogenous glucose production (EGP) in the postabsorptive state and during variable hyperglycemic-hyperinsulinemic infusions.. Prospective, nonrandomized study.. Academic research environment.. Twelve hyperandrogenic anovulatory patients and 11 healthy women matched by body mass index and waist to hip circumference ratio.. Variable hyperglycemic-hyperinsulinemic infusions replicated physiological increases in circulating glucose and insulin levels before and after 3-month GnRH-a administration.. Glucose utilization and EGP.. In the postabsorptive state, plasma glucose and insulin levels, glucose utilization, and EGP were similar in hyperandrogenic patients and healthy women. During variable hyperglycemic-hyperinsulinemic infusions, glucose use increased and EGP decreased to similar degrees in both groups of women. Three-month GnRH-a administration to hyperandrogenic patients and healthy women did not affect plasma glucose and insulin levels, glucose utilization and EGP in the postabsorptive state, or glucose utilization and EGP during variable hyperglycemic-hyperinsulinemic infusions.. Glucose use and EGP in the postabsorptive state and during variable hyperglycemic-hyperinsulinemic infusions are similar in hyperandrogenic anovulatory patients and healthy women of similar body fat distribution and are unaffected by 3-month GnRH-a administration.

Topics: Adolescent; Adrenal Glands; Adult; Anovulation; Blood Glucose; Body Composition; C-Peptide; Female; Glucagon; Human Growth Hormone; Humans; Hyperandrogenism; Insulin; Insulin Resistance; Leuprolide; Middle Aged; Ovary; Prospective Studies; Steroids

Insulin secretion in response to an oral glucose tolerance test (OGTT) and sex hormone levels (free testosterone, androstenedione, dehydroepiandrosterone sulfate [DHEAS], estradiol, and sex hormone-binding globulin [SHBG]) were evaluated in 49 healthy obese premenopausal women (body mass index [BMI], 30 to 50.6 kg/m2) and 21 control subjects (BMI, 17.8 to 24.0 kg/m2) with normal glucose tolerance and without signs of hyperandrogenism. Obese women were divided into two groups according to waist to hip ratio (WHR): 27 subjects with upper-body obesity (WHR > 0.85) and 22 subjects with lower-body obesity (WHR < 0.8). Both fasting and glucose-induced insulin levels were higher in women with upper-body obesity than in controls (P < .001) and those with lower-body obesity (P < .001). Hyperandrogenism was observed in women with upper-body obesity, as evident by significantly elevated free testosterone (P < .05 v controls and subjects with lower-body obesity) and decreased SHBG (P < .001 v controls). The most important independent determinants of fasting insulin levels were BMI (P < .01) and the ratio of DHEAS to free testosterone (P < .01). The most important determinants of cumulative insulin response were WHR (P < .0005), duration of obesity (P < .01), and androstenedione levels (P < .01). In conclusion, in healthy obese premenopausal women without clinical signs of hyperandrogenism, a high BMI and more pronounced upper-body fat localization resulted in hyperinsulinemia and hyperandrogenism. The duration of obesity exaggerated the glucose-induced insulin level and cumulative insulin response independently of the degree of obesity and obesity type. The ratio of DHEAS to free testosterone was an independent determinant of fasting insulin concentration. Furthermore, the ratio of DHEAS to free testosterone rather than either of these androgens alone may be important in the regulation of insulin action in women.

Topics: Adult; Androstenedione; Body Weight; C-Peptide; Dehydroepiandrosterone; Estradiol; Fasting; Female; Glucose; Glucose Tolerance Test; Gonadal Steroid Hormones; Humans; Hyperandrogenism; Hyperinsulinism; Insulin; Obesity; Premenopause; Regression Analysis; Sex Hormone-Binding Globulin; Testosterone

To further investigate the relationship between inappropriate gonadotropin, hyperinsulinemia and androgen excess.. We divided women with polycystic ovarian syndrome (PCOS) into two groups on the basis of LH/FSH (LH/FSH > or = 3, Group 1, n=30; LH/FSH<3, Group 2, n=25) and measured the responses of insulin, C-peptide (C-P), C-P/insulin (C-I) and testosterone concentrations to an oral glucose tolerance test (OGTT) in these patients and 15 control subjects.. Significant positive correlations were found between basal LH and T (r=O.58, p<0.05) in Group 1, and between fasting serum insulin and T (r=0.48, p<0.05) in Group 2. Although these patients had higher, delayed insulin and C-P responses to OGTT than the control group, much greater insulin and C-P levels and lower C/I values were found in Group 2. T concentrations decreased mildly during OGTT in Group 1 and the control, while they increased slightly in Group 2.. Our data suggest that hyperinsulinemia in PCOS is due to a enhanced beta-cell secretion and an impaired hepatic clearance of this hormone, hyperandrogenism may be LH-dependent in Group 1 and insulin-dependent in Group 2.

Topics: Adult; Analysis of Variance; C-Peptide; Female; Follicle Stimulating Hormone; Glucose; Glucose Tolerance Test; Humans; Hyperandrogenism; Insulin; Luteinizing Hormone; Polycystic Ovary Syndrome; Testosterone

Previous studies have documented the association of insulin resistance and hyperandrogenism in adult women with functional ovarian hyperandrogenism (FOH) or polycystic ovary syndrome (a form of FOH). However, the possible impact of adrenal hyperandrogenism development during childhood in premature pubarche (PP) patients on postpubertal insulin secretion patterns remains unclear. The fasting insulin to glucose ratio, C peptide, early insulin response to glucose (IRG), mean blood glucose, mean serum insulin (MSI), glucose uptake rate in peripheral tissues (M), and insulin sensitivity indexes (SI) in response to a standard oral glucose tolerance test were evaluated in 13 PP girls with FOH (group A; age, 17.2 +/- 0.5 yr), 11 eumenorrheic nonhirsute PP girls (group B; age, 16.6 +/- 0.5 yr), and 21 age-matched controls (group C). Body mass indexes (BMI) were similar in the 3 groups (group A, 23.3 +/- 0.8; group B, 22.5 +/- 0.6; group C, 20.6 +/- 0.5 kg/m2). MSI values were significantly higher in FOH patients than in controls (74.7 +/- 17.6 vs. 45.7 +/- 4.1 mU/L; P < 0.01), but were not different from those in group B (63.3 +/- 11.1 mU/L). Thirty-eight percent of FOH patients (group A) and 27% of non-FOH patients (group B), all of whom had normal BMI, showed MSI levels well above the upper normal limit for controls (> 83.3 mU/L). MSI correlated with the degree of ovarian hyperandrogenism [defined by an abnormal 17-hydroxyprogesterone response to challenge with the GnRH analog leuprolide acetate; group A] and with the free androgen index [testosterone (nanomoles per L)/sex hormone-binding globulin (nanomoles per L) x 100; groups A and B)]. Although IRG, glucose uptake rate in peripheral tissues, mean blood glucose, and SI values were not significantly different in the 3 groups, 3 patients in group A and 1 patient in group B showed decreased insulin sensitivity and/or an enhanced early IRG. Among others, significant correlations between MSI and free androgen index values (r = 0.6; P < 0.002; groups A and B) and between BMI and SI (r = -0.53; P < 0.05; groups A and B) were found. Peak 17-hydroxyprogesterone responses to ACTH at PP diagnosis correlated positively with SI in both groups of patients (r = 0.53; P < 0.007). Hyperinsulinemia is a common feature in adolescent PP patients with FOH and appears to be directly related to the degree of androgen excess. Long term follow-up of PP patients into adulthood is warranted to ascertain whether hyperinsulinemia actuall

Topics: Adolescent; Androgens; Blood Glucose; C-Peptide; Female; Hair; Humans; Hyperandrogenism; Hyperinsulinism; Insulin; Insulin Secretion; Medical Records; Ovary; Puberty; Sexual Maturation