Scandinavian journal of clinical and laboratory investigation. Supplementum, 2014
Young women with polycystic ovary syndrome (PCOS) present an increased risk for type II diabetes ... more Young women with polycystic ovary syndrome (PCOS) present an increased risk for type II diabetes and cardiovascular diseases. The prevalence of altered glucose tolerance ranges between 20 and 35 % in patients while the prevalence of type II diabetes ranges between 2 and 8 % and seems related to body weight and ethnic group. Moving from the young fertile age to the 40s and the menopause the prevalence of type II diabetes continues to increase compared to the general female population and may reach 10-16 % of PCOS women. However, prevalence of altered glucose tolerance does not increase. Also cardiovascular risk is increased in a large part of young PCOS women but this risk tends to be normalized with age because of the reduction of ovarian androgen secretion and occurrence of ovulatory cycles in at least one third of PCOS women approaching menopause. It may explain the discrepancy between cardiovascular (CV) risk during young age and observed number of CV events. Long-term management...
New guidelines regarding diagnosis of polycystic ovary syndrome have been published recently. The... more New guidelines regarding diagnosis of polycystic ovary syndrome have been published recently. The traditional way of making the diagnosis is guided by US National Health Institute. But many experts contradicted the method of diagnosis. An agreement was found on the new guidelines at a joint meeting of ESHRE and ASRM in 2004. At the same meeting new criteria for sonographic diagnosis were suggested. The new guidelines for diagnosis of polycystic ovary syndrome have represented a reasonable compromise between different opinions and because of it they have got a great success. During 2005 a consensus conference and a special expert committee have evaluated the new guidelines and reached some conclusion. That is likely to be published in future. The diagnostic study is not complete without an evaluation of metabolic and cardiovascular risk factors. Only a better understanding of the pathogenesis of polycystic ovary syndrome can definitely establish the diagnostic criteria.
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by the pathogenetic im... more Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by the pathogenetic importance of ovarian hyperandrogenism and insulin resistance and by the variable presence of four key features: (1) chronic anovulation; (2) hyperandrogenism; (3) abdominal obesity; and (4) polycystic ovaries [1].
Several beneficial effects produced by statins over and above the reduction in plasma cholesterol... more Several beneficial effects produced by statins over and above the reduction in plasma cholesterol levels, the so-called ''pleiotropic effects'' of statins, have been described. Recent clinical and experimental data have suggested a potential new effect of these drugs, namely a reduction in the risk of osteoporotic fractures. In 1999 the role of statins in bone formation was shown and, after that, observations of large groups of patients have pointed to a reduction in the risk of osteoporotic fractures with the use of statins compared to those using other lipid-lowering drugs or to the control group. The first prospective studies have produced contrasting results as to the effects of therapy with several statins (atorvastatin, fluvastatin, simvastatin) at different doses on biochemical markers of bone remodelling. To date only one randomised trial has been published. This compares the effects of treatment with simvastatin and atorvastatin on the levels of biochemical markers of bone remodelling, but still with non-univocal results: only therapy with simvastatin (but not atorvastatin) reduced the levels of bone-specific alkaline phosphatase. To conclude, observational studies have shown a reduction in the risk of osteoporotic fractures with the use of statins, but it is not yet known whether using these drugs may have a beneficial effect on bone turnover. We must therefore await larger prospective randomised clinical trials before prescribing these drugs in osteoporotic patients.
Cardiovascular diseases represent the major cause of death in most of developed countries and ult... more Cardiovascular diseases represent the major cause of death in most of developed countries and ultimately kill as many men as women. Both genders are exposed to the same risk factors but their rates of cardiovascular morbidity and mortality are very different until old age. This represents a crucial point; in fact, only at age 75 and over cardiovascular rates of women approximate those of men. It has been suggested that differences in hormonal status and mainly in androgen levels may explain such gender disparity. Consistently with this hypothesis, it has been shown that women with polycystic ovary syndrome (PCOS) have elevated cardiovascular risk despite their young age. However, the possibility that androgens may increase cardiovascular risk remains controversial. Hyperandrogenism, as isolated androgen excess, has not been clearly recognised so far as a risk factor for cardiovascular diseases. In addition, the risk of premature cardiovascular diseases in PCOS is at present uncertain. Long-term studies examining the prevalence of cardiovascular diseases among women with PCOS did not demonstrate a clear increased risk for cardiovascular morbidity and mortality. Thus, it seems that androgens have a limited role in inducing cardiovascular risk; the altered risk factors found in women with PCOS are mainly dependent on the metabolic components of this syndrome as well as on insulin resistance and reduced adiponectin secretion.
Mucormycosis is a rare invasive mycotic infection treated by antifungini or amphotericin B. We de... more Mucormycosis is a rare invasive mycotic infection treated by antifungini or amphotericin B. We describe the case of a patient with septic fever and a necrotic lesion, with phlegmon of medial left thigh. Surgery was performed to drain the abscess content and to remove the necrotic tissue; mucormycosis was diagnosized by histological and culture tests and treated by intravenous amphotericin B. Since the lesion worsened, liposomal amphotericin B was directly infused into the left common iliac artery, with progressive improvement, and treatment was continued until complete recovery. Therefore, the endoarterial infusion of liposomal amphotericin B was a safe and successful treatment of advanced lesions of mucormycosis. In such lesions, intravenous general antibiotic administration probably is not sufficient to reach the whole infected area.
The Journal of Steroid Biochemistry and Molecular Biology, 2015
Approximately 20-30% of PCOS women demonstrate excess adrenal precursor androgen (APA) production... more Approximately 20-30% of PCOS women demonstrate excess adrenal precursor androgen (APA) production, primarily using DHEAS as a marker of APA in general and more specifically DHEA, synthesis. The role of APA excess in determining or causing PCOS is unclear, although observations in patients with inherited APA excess (e.g., patients with 21-hydroxylase deficient congenital classic or nonclassic adrenal hyperplasia) demonstrate that APA excess can result in a PCOS-like phenotype. Inherited defects of the enzymes responsible for steroid biosynthesis, or defects in cortisol metabolism, account for only a very small fraction of women suffering from hyperandrogenism or APA excess. Rather, women with PCOS and APA excess appear to have a generalized exaggeration in adrenal steroidogenesis in response to ACTH stimulation, although they do not have overt hypothalamic-pituitary-adrenal axis dysfunction. In general, extra-adrenal factors, including obesity, insulin and glucose levels, and ovarian secretions, play a limited role in the increased APA production observed in PCOS. Substantial heritabilities of APAs, particularlyDHEAS,havebeenfoundinthegeneralpopulationandinwomenwithPCOS;however,thehandful of SNPs discovered to date accountonly for a small portion of the inheritance of these traits. Paradoxically, and asinmen,elevatedlevelsofDHEASappeartobeprotective againstcardiovascularrisk inwomen,althoughthe role of DHEAS in modulating this risk in women with PCOS remains unknown. In summary, the exact cause of APA excess in PCOS remains unclear, although it may reflect a generalized and inherited exaggeration in androgen biosynthesis of an inherited nature.
To reevaluate the clinical significance of elevations of adrenal androgens in polycystic ovary sy... more To reevaluate the clinical significance of elevations of adrenal androgens in polycystic ovary syndrome (PCOS). Thirty women with PCOS and ten ovulatory controls were evaluated. Serum dehydroepiandrosterone (DHEA) sulfate and 11 beta-hydroxyandrostenedione were measured before and after 3 and 6 months of GnRH agonist (GnRH-A) therapy. All controls and 15 women with PCOS received intravenous ACTH before and after GnRH-A therapy. Twenty-one (70%) of the women with PCOS had elevations of DHEA sulfate, and 16 (53%) had elevations in 11 beta-hydroxyandrostenedione. Only two women with PCOS had normal values of both adrenal androgens. After GnRH-A therapy, only 11 subjects (37%) had elevated values of DHEA sulfate. Four of 16 women had reductions in 11 beta-hydroxyandrostenedione. Only those with elevated baseline DHEA sulfate levels had reductions after GnRH-A therapy. The reduction of DHEA sulfate with GnRH-A correlated with the reduction in androstenedione. Of the subjects who had reductions in DHEA sulfate with GnRH-A therapy, there was a blunted response of DHEA to ACTH after treatment. Our findings suggest that the ovary may influence the prevalence and magnitude of adrenal androgen excess in PCOS.
The Journal of Clinical Endocrinology & Metabolism, 2000
Women with polycystic ovary syndrome (PCOS) have chronic anovulation and hyperandrogenism and fre... more Women with polycystic ovary syndrome (PCOS) have chronic anovulation and hyperandrogenism and frequently have abnormalities in their lipid profiles and insulin/insulin-like growth factor axis that increase their lifetime risk for cardiovascular disease. Normal ovulatory women may have polycystic ovaries on ultrasonography and yet lack the clinical features of PCOS. To further explore whether ovulatory women without clinical/biochemical hyperandrogenism but with polycystic appearing ovaries (ov-PAO) have subclinical features of PCOS, we prospectively characterized 26 ov-PAO women and matched them by age and body mass index to 25 ovulatory women with normal appearing ovaries (ov-NAO) and to 22 women with PCOS. After an overnight fast, all women had baseline endocrine and metabolic assessments. In addition, a subset of each group of women underwent GnRH-agonist (leuprolide acetate 1 mg sc) testing, ACTH stimulation, and an insulin tolerance test (ITT). At baseline, ov-PAO and ov-NAO women had similar endocrine profiles (LH, LH:FSH,
International Journal of Gynecology & Obstetrics, 2009
To determine which adipocytokines are differentially expressed as a function of body mass index (... more To determine which adipocytokines are differentially expressed as a function of body mass index (BMI), to compare expression of adipocytokines in abdominal subcutaneous and omental fat, and to correlate these findings with serum levels, BMI, and parameters of insulin resistance. Serum and subcutaneous (sc) and omental (om) tissue were obtained from lean and obese ovulatory women undergoing gynecologic surgery. We determined adipocytokine expression in sc versus om abdominal fat and related this to increasing BMI. Serum leptin was higher and adiponectin lower in overweight subjects. Adipocytokines had higher expression in sc abdominal versus om adipose tissue with the most significant difference observed for leptin (P=0.01). As BMI increased, sc leptin expression increased and adiponectin expression decreased. The leptin/adiponectin ratio correlated significantly with BMI (R=0.84, P=0.0001). Increased adipocytokine expression correlates with BMI. Abdominal sc tissue has greater adipocytokine expression overall. The serum leptin/adiponectin ratio is highly correlated with BMI. These data may help in our understanding of how obesity affects women in a variety of ways.
Adrenal hyperandrogenism is prevalent in many women with polycystic ovary syndrome (PCOS), althou... more Adrenal hyperandrogenism is prevalent in many women with polycystic ovary syndrome (PCOS), although the expression of this enhanced secretion may be heterogeneous. Since no single factor acts in isolation, this study was performed to assess the influence of oestradiol (total and unbound), insulin, insulin-like growth factor (IGF)-I, IGF-II and the binding proteins IGFBP-I, and IGFBP-3, on basal and adrenocorticotrophic hormone (ACTH) stimulated adrenal androgen secretion in 25 women with PCOS and 10 matched ovulatory controls. Women with PCOS exhibited elevations of all androgens as well as unbound oestradiol, insulin and non-IGFBP-1 bound IGF-I. Positive correlations were noted between oestrogen and basal and ACTH stimulated ∆ 5 adrenal androgens. Serum IGF-I was only correlated with basal dehydroepiandrosterone sulphate (DHEA-S), while insulin exhibited a strong correlation with the ∆ 4 pathway and androstenedione formation in particular. This correlation was also confirmed by dividing the PCOS group into those women with and without hyperinsulinaemia. The activity of 17,20 lyase favouring androstenedione was increased in the hyperinsulinaemic women. By multivariate analyses, body mass index did not influence these findings. Although there are inherent difficulties in making major conclusions based on correlative analyses, it is suggested that oestrogen may have a greater influence on enhancing ∆ 5 adrenal androgen secretion, and insulin a greater effect on the ∆ 4 pathway. In turn, the relative importance of these influences may contribute to the heterogeneous nature of adrenal hyperandrogenism in PCOS.
Objective: Although serum leptin is principally influenced by body mass, to understand the role o... more Objective: Although serum leptin is principally influenced by body mass, to understand the role of insulin and androgens in the regulation of serum leptin in normal weight women. Design: Prospective observational study. Setting: Academic practice in reproductive endocrinology. Patient(s): Twenty-one women with polycystic ovary syndrome (PCOS) of normal body weight, 8 apparently normal women with polycystic-appearing ovaries (PAO), and 21 normal women. Intervention(s): Fasting blood levels of luteinizing hormone, follicle-stimulating hormone, testosterone (T), unbound T, dehydroepiandrosterone sulfate (DHEAS), insulin, insulin growth factor-binding protein-1 (IGFBP-1), and leptin. Main Outcome Measure(s): Comparisons of measured hormones in the different groups and correlative analysis Result(s): Women with PCOS had higher levels of serum luteinizing hormone, T, unbound T, DHEAS and insulin, and lower levels of IGFBP-1 compared with the normal controls, but they had similar leptin levels. Normal women with PAO had increased levels of insulin and leptin compared with controls, whereas IGFBP-1 was lower in PAO. In normal weight women with PCOS and PAO, leptin correlated positively with body weight and insulin, and negatively with IGFBP-1 and DHEAS.
A better understanding of the different phenotypes and of their endocrine and metabolic character... more A better understanding of the different phenotypes and of their endocrine and metabolic characteristics permits investigators to distinguish three main androgen excess disorders: classic polycystic ovary syndrome (PCOS), mild ovulatory PCOS, and idiopathic hyperandrogenism. These androgenic phenotypes differ more for the severity of the endocrine and metabolic alteration than for the etiopathogenetic mechanisms. The appearance of a particular androgenic phenotype is determined by a sum of genetic and environmental factors, but mostly by body weight. (Fertil Steril 2006;85:1582-5.
Scandinavian journal of clinical and laboratory investigation. Supplementum, 2014
Young women with polycystic ovary syndrome (PCOS) present an increased risk for type II diabetes ... more Young women with polycystic ovary syndrome (PCOS) present an increased risk for type II diabetes and cardiovascular diseases. The prevalence of altered glucose tolerance ranges between 20 and 35 % in patients while the prevalence of type II diabetes ranges between 2 and 8 % and seems related to body weight and ethnic group. Moving from the young fertile age to the 40s and the menopause the prevalence of type II diabetes continues to increase compared to the general female population and may reach 10-16 % of PCOS women. However, prevalence of altered glucose tolerance does not increase. Also cardiovascular risk is increased in a large part of young PCOS women but this risk tends to be normalized with age because of the reduction of ovarian androgen secretion and occurrence of ovulatory cycles in at least one third of PCOS women approaching menopause. It may explain the discrepancy between cardiovascular (CV) risk during young age and observed number of CV events. Long-term management...
New guidelines regarding diagnosis of polycystic ovary syndrome have been published recently. The... more New guidelines regarding diagnosis of polycystic ovary syndrome have been published recently. The traditional way of making the diagnosis is guided by US National Health Institute. But many experts contradicted the method of diagnosis. An agreement was found on the new guidelines at a joint meeting of ESHRE and ASRM in 2004. At the same meeting new criteria for sonographic diagnosis were suggested. The new guidelines for diagnosis of polycystic ovary syndrome have represented a reasonable compromise between different opinions and because of it they have got a great success. During 2005 a consensus conference and a special expert committee have evaluated the new guidelines and reached some conclusion. That is likely to be published in future. The diagnostic study is not complete without an evaluation of metabolic and cardiovascular risk factors. Only a better understanding of the pathogenesis of polycystic ovary syndrome can definitely establish the diagnostic criteria.
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by the pathogenetic im... more Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by the pathogenetic importance of ovarian hyperandrogenism and insulin resistance and by the variable presence of four key features: (1) chronic anovulation; (2) hyperandrogenism; (3) abdominal obesity; and (4) polycystic ovaries [1].
Several beneficial effects produced by statins over and above the reduction in plasma cholesterol... more Several beneficial effects produced by statins over and above the reduction in plasma cholesterol levels, the so-called ''pleiotropic effects'' of statins, have been described. Recent clinical and experimental data have suggested a potential new effect of these drugs, namely a reduction in the risk of osteoporotic fractures. In 1999 the role of statins in bone formation was shown and, after that, observations of large groups of patients have pointed to a reduction in the risk of osteoporotic fractures with the use of statins compared to those using other lipid-lowering drugs or to the control group. The first prospective studies have produced contrasting results as to the effects of therapy with several statins (atorvastatin, fluvastatin, simvastatin) at different doses on biochemical markers of bone remodelling. To date only one randomised trial has been published. This compares the effects of treatment with simvastatin and atorvastatin on the levels of biochemical markers of bone remodelling, but still with non-univocal results: only therapy with simvastatin (but not atorvastatin) reduced the levels of bone-specific alkaline phosphatase. To conclude, observational studies have shown a reduction in the risk of osteoporotic fractures with the use of statins, but it is not yet known whether using these drugs may have a beneficial effect on bone turnover. We must therefore await larger prospective randomised clinical trials before prescribing these drugs in osteoporotic patients.
Cardiovascular diseases represent the major cause of death in most of developed countries and ult... more Cardiovascular diseases represent the major cause of death in most of developed countries and ultimately kill as many men as women. Both genders are exposed to the same risk factors but their rates of cardiovascular morbidity and mortality are very different until old age. This represents a crucial point; in fact, only at age 75 and over cardiovascular rates of women approximate those of men. It has been suggested that differences in hormonal status and mainly in androgen levels may explain such gender disparity. Consistently with this hypothesis, it has been shown that women with polycystic ovary syndrome (PCOS) have elevated cardiovascular risk despite their young age. However, the possibility that androgens may increase cardiovascular risk remains controversial. Hyperandrogenism, as isolated androgen excess, has not been clearly recognised so far as a risk factor for cardiovascular diseases. In addition, the risk of premature cardiovascular diseases in PCOS is at present uncertain. Long-term studies examining the prevalence of cardiovascular diseases among women with PCOS did not demonstrate a clear increased risk for cardiovascular morbidity and mortality. Thus, it seems that androgens have a limited role in inducing cardiovascular risk; the altered risk factors found in women with PCOS are mainly dependent on the metabolic components of this syndrome as well as on insulin resistance and reduced adiponectin secretion.
Mucormycosis is a rare invasive mycotic infection treated by antifungini or amphotericin B. We de... more Mucormycosis is a rare invasive mycotic infection treated by antifungini or amphotericin B. We describe the case of a patient with septic fever and a necrotic lesion, with phlegmon of medial left thigh. Surgery was performed to drain the abscess content and to remove the necrotic tissue; mucormycosis was diagnosized by histological and culture tests and treated by intravenous amphotericin B. Since the lesion worsened, liposomal amphotericin B was directly infused into the left common iliac artery, with progressive improvement, and treatment was continued until complete recovery. Therefore, the endoarterial infusion of liposomal amphotericin B was a safe and successful treatment of advanced lesions of mucormycosis. In such lesions, intravenous general antibiotic administration probably is not sufficient to reach the whole infected area.
The Journal of Steroid Biochemistry and Molecular Biology, 2015
Approximately 20-30% of PCOS women demonstrate excess adrenal precursor androgen (APA) production... more Approximately 20-30% of PCOS women demonstrate excess adrenal precursor androgen (APA) production, primarily using DHEAS as a marker of APA in general and more specifically DHEA, synthesis. The role of APA excess in determining or causing PCOS is unclear, although observations in patients with inherited APA excess (e.g., patients with 21-hydroxylase deficient congenital classic or nonclassic adrenal hyperplasia) demonstrate that APA excess can result in a PCOS-like phenotype. Inherited defects of the enzymes responsible for steroid biosynthesis, or defects in cortisol metabolism, account for only a very small fraction of women suffering from hyperandrogenism or APA excess. Rather, women with PCOS and APA excess appear to have a generalized exaggeration in adrenal steroidogenesis in response to ACTH stimulation, although they do not have overt hypothalamic-pituitary-adrenal axis dysfunction. In general, extra-adrenal factors, including obesity, insulin and glucose levels, and ovarian secretions, play a limited role in the increased APA production observed in PCOS. Substantial heritabilities of APAs, particularlyDHEAS,havebeenfoundinthegeneralpopulationandinwomenwithPCOS;however,thehandful of SNPs discovered to date accountonly for a small portion of the inheritance of these traits. Paradoxically, and asinmen,elevatedlevelsofDHEASappeartobeprotective againstcardiovascularrisk inwomen,althoughthe role of DHEAS in modulating this risk in women with PCOS remains unknown. In summary, the exact cause of APA excess in PCOS remains unclear, although it may reflect a generalized and inherited exaggeration in androgen biosynthesis of an inherited nature.
To reevaluate the clinical significance of elevations of adrenal androgens in polycystic ovary sy... more To reevaluate the clinical significance of elevations of adrenal androgens in polycystic ovary syndrome (PCOS). Thirty women with PCOS and ten ovulatory controls were evaluated. Serum dehydroepiandrosterone (DHEA) sulfate and 11 beta-hydroxyandrostenedione were measured before and after 3 and 6 months of GnRH agonist (GnRH-A) therapy. All controls and 15 women with PCOS received intravenous ACTH before and after GnRH-A therapy. Twenty-one (70%) of the women with PCOS had elevations of DHEA sulfate, and 16 (53%) had elevations in 11 beta-hydroxyandrostenedione. Only two women with PCOS had normal values of both adrenal androgens. After GnRH-A therapy, only 11 subjects (37%) had elevated values of DHEA sulfate. Four of 16 women had reductions in 11 beta-hydroxyandrostenedione. Only those with elevated baseline DHEA sulfate levels had reductions after GnRH-A therapy. The reduction of DHEA sulfate with GnRH-A correlated with the reduction in androstenedione. Of the subjects who had reductions in DHEA sulfate with GnRH-A therapy, there was a blunted response of DHEA to ACTH after treatment. Our findings suggest that the ovary may influence the prevalence and magnitude of adrenal androgen excess in PCOS.
The Journal of Clinical Endocrinology & Metabolism, 2000
Women with polycystic ovary syndrome (PCOS) have chronic anovulation and hyperandrogenism and fre... more Women with polycystic ovary syndrome (PCOS) have chronic anovulation and hyperandrogenism and frequently have abnormalities in their lipid profiles and insulin/insulin-like growth factor axis that increase their lifetime risk for cardiovascular disease. Normal ovulatory women may have polycystic ovaries on ultrasonography and yet lack the clinical features of PCOS. To further explore whether ovulatory women without clinical/biochemical hyperandrogenism but with polycystic appearing ovaries (ov-PAO) have subclinical features of PCOS, we prospectively characterized 26 ov-PAO women and matched them by age and body mass index to 25 ovulatory women with normal appearing ovaries (ov-NAO) and to 22 women with PCOS. After an overnight fast, all women had baseline endocrine and metabolic assessments. In addition, a subset of each group of women underwent GnRH-agonist (leuprolide acetate 1 mg sc) testing, ACTH stimulation, and an insulin tolerance test (ITT). At baseline, ov-PAO and ov-NAO women had similar endocrine profiles (LH, LH:FSH,
International Journal of Gynecology & Obstetrics, 2009
To determine which adipocytokines are differentially expressed as a function of body mass index (... more To determine which adipocytokines are differentially expressed as a function of body mass index (BMI), to compare expression of adipocytokines in abdominal subcutaneous and omental fat, and to correlate these findings with serum levels, BMI, and parameters of insulin resistance. Serum and subcutaneous (sc) and omental (om) tissue were obtained from lean and obese ovulatory women undergoing gynecologic surgery. We determined adipocytokine expression in sc versus om abdominal fat and related this to increasing BMI. Serum leptin was higher and adiponectin lower in overweight subjects. Adipocytokines had higher expression in sc abdominal versus om adipose tissue with the most significant difference observed for leptin (P=0.01). As BMI increased, sc leptin expression increased and adiponectin expression decreased. The leptin/adiponectin ratio correlated significantly with BMI (R=0.84, P=0.0001). Increased adipocytokine expression correlates with BMI. Abdominal sc tissue has greater adipocytokine expression overall. The serum leptin/adiponectin ratio is highly correlated with BMI. These data may help in our understanding of how obesity affects women in a variety of ways.
Adrenal hyperandrogenism is prevalent in many women with polycystic ovary syndrome (PCOS), althou... more Adrenal hyperandrogenism is prevalent in many women with polycystic ovary syndrome (PCOS), although the expression of this enhanced secretion may be heterogeneous. Since no single factor acts in isolation, this study was performed to assess the influence of oestradiol (total and unbound), insulin, insulin-like growth factor (IGF)-I, IGF-II and the binding proteins IGFBP-I, and IGFBP-3, on basal and adrenocorticotrophic hormone (ACTH) stimulated adrenal androgen secretion in 25 women with PCOS and 10 matched ovulatory controls. Women with PCOS exhibited elevations of all androgens as well as unbound oestradiol, insulin and non-IGFBP-1 bound IGF-I. Positive correlations were noted between oestrogen and basal and ACTH stimulated ∆ 5 adrenal androgens. Serum IGF-I was only correlated with basal dehydroepiandrosterone sulphate (DHEA-S), while insulin exhibited a strong correlation with the ∆ 4 pathway and androstenedione formation in particular. This correlation was also confirmed by dividing the PCOS group into those women with and without hyperinsulinaemia. The activity of 17,20 lyase favouring androstenedione was increased in the hyperinsulinaemic women. By multivariate analyses, body mass index did not influence these findings. Although there are inherent difficulties in making major conclusions based on correlative analyses, it is suggested that oestrogen may have a greater influence on enhancing ∆ 5 adrenal androgen secretion, and insulin a greater effect on the ∆ 4 pathway. In turn, the relative importance of these influences may contribute to the heterogeneous nature of adrenal hyperandrogenism in PCOS.
Objective: Although serum leptin is principally influenced by body mass, to understand the role o... more Objective: Although serum leptin is principally influenced by body mass, to understand the role of insulin and androgens in the regulation of serum leptin in normal weight women. Design: Prospective observational study. Setting: Academic practice in reproductive endocrinology. Patient(s): Twenty-one women with polycystic ovary syndrome (PCOS) of normal body weight, 8 apparently normal women with polycystic-appearing ovaries (PAO), and 21 normal women. Intervention(s): Fasting blood levels of luteinizing hormone, follicle-stimulating hormone, testosterone (T), unbound T, dehydroepiandrosterone sulfate (DHEAS), insulin, insulin growth factor-binding protein-1 (IGFBP-1), and leptin. Main Outcome Measure(s): Comparisons of measured hormones in the different groups and correlative analysis Result(s): Women with PCOS had higher levels of serum luteinizing hormone, T, unbound T, DHEAS and insulin, and lower levels of IGFBP-1 compared with the normal controls, but they had similar leptin levels. Normal women with PAO had increased levels of insulin and leptin compared with controls, whereas IGFBP-1 was lower in PAO. In normal weight women with PCOS and PAO, leptin correlated positively with body weight and insulin, and negatively with IGFBP-1 and DHEAS.
A better understanding of the different phenotypes and of their endocrine and metabolic character... more A better understanding of the different phenotypes and of their endocrine and metabolic characteristics permits investigators to distinguish three main androgen excess disorders: classic polycystic ovary syndrome (PCOS), mild ovulatory PCOS, and idiopathic hyperandrogenism. These androgenic phenotypes differ more for the severity of the endocrine and metabolic alteration than for the etiopathogenetic mechanisms. The appearance of a particular androgenic phenotype is determined by a sum of genetic and environmental factors, but mostly by body weight. (Fertil Steril 2006;85:1582-5.
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