Polycystic ovary syndrome

High testosterone, dihydrotestosterone linked to adverse metabolic phenotype in patients with PCOS

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Patients with polycystic ovary syndrome who have a high testosterone to dihydrotestosterone ratio appear to be more likely to have an adverse metabolic phenotype, according to recent findings.

In the study, researchers evaluated 275 premenopausal women aged 16 to 48 years with PCOS and 35 BMI-matched, premenopausal, health women aged 21 to 50 years as controls. The researchers recorded anthropometric data for all participants, including height, weight, waist circumference and hip circumference.

Researchers recorded systolic and diastolic blood pressure measurements and calculated BMI. Fasting blood samples were taken to evaluate basal hormone serum levels. Additionally, an oral glucose tolerance test was performed, and blood samples were collected at 30, 60 and 120 minutes to determine glucose and insulin concentrations.

A routine method for liquid chromatography/mass spectrometry was used to determine total testosterone (T), total dihydrotestosterone (DHT), androstenedione and dehydroepiandrosterone (DHEA).

The researchers found that patients with PCOS had significantly higher levels of total T (P<.001), free testosterone (P<.001) and free DHT (P<.001) vs. healthy controls. Additionally, patients with PCOS had a significantly higher total T/DHT ratio (P<.001). No difference was found between PCOS and control participants in terms of total DHT levels (P=.072).

An analysis of just patients with PCOS revealed a significantly higher total T/DHT ratio in patients with obesity (P<.001) as well as those with metabolic syndrome (P<.001), impaired glucose tolerance (P<.001) or insulin resistance (P<.001).

The researchers also found significant association between total T/DHT ratio and various adverse anthropometric, hormonal, lipid and liver measures, and measures of glucose tolerance.

“This correlation was only found in PCOS patients, suggesting the [total] T/DHT ratio is a new biomarker for an adverse metabolic phenotype in PCOS patients,” the researchers wrote. “Nevertheless, future studies and larger trials are needed for the evaluation of results.”

High testosterone, dihydrotestosterone linked to adverse metabolic phenotype in patients with PCOS

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Patients with polycystic ovary syndrome who have a high testosterone to dihydrotestosterone ratio appear to be more likely to have an adverse metabolic phenotype, according to recent findings.

In the study, researchers evaluated 275 premenopausal women aged 16 to 48 years with PCOS and 35 BMI-matched, premenopausal, health women aged 21 to 50 years as controls. The researchers recorded anthropometric data for all participants, including height, weight, waist circumference and hip circumference.

Researchers recorded systolic and diastolic blood pressure measurements and calculated BMI. Fasting blood samples were taken to evaluate basal hormone serum levels. Additionally, an oral glucose tolerance test was performed, and blood samples were collected at 30, 60 and 120 minutes to determine glucose and insulin concentrations.

A routine method for liquid chromatography/mass spectrometry was used to determine total testosterone (T), total dihydrotestosterone (DHT), androstenedione and dehydroepiandrosterone (DHEA).

The researchers found that patients with PCOS had significantly higher levels of total T (P<.001), free testosterone (P<.001) and free DHT (P<.001) vs. healthy controls. Additionally, patients with PCOS had a significantly higher total T/DHT ratio (P<.001). No difference was found between PCOS and control participants in terms of total DHT levels (P=.072).

An analysis of just patients with PCOS revealed a significantly higher total T/DHT ratio in patients with obesity (P<.001) as well as those with metabolic syndrome (P<.001), impaired glucose tolerance (P<.001) or insulin resistance (P<.001).

The researchers also found significant association between total T/DHT ratio and various adverse anthropometric, hormonal, lipid and liver measures, and measures of glucose tolerance.

“This correlation was only found in PCOS patients, suggesting the [total] T/DHT ratio is a new biomarker for an adverse metabolic phenotype in PCOS patients,” the researchers wrote. “Nevertheless, future studies and larger trials are needed for the evaluation of results.”

PCOS increased risk for CVD, obesity.

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In a case-control study, researchers found that young women with polycystic ovary syndrome have a higher prevalence of cardiovascular disease risk factors, including hypertension, obesity and metabolic syndrome, compared with controls. The researchers also found significantly lower levels of lipoprotein apolipoprotein A-I and observed a significant reduction in efflux capacity.

  • “Given the available data, there is evidence to suggest that women with PCOS are at an increased risk for developing CV-related outcomes,” Andrea Roe, MD, of the department of obstetrics and gynecology in the division of reproductive endocrinology at the University of Pennsylvania, and colleagues wrote. “These data strongly support educating all PCOS patients about the associated risk of dyslipidemia and need for frequent lipid screening.”

The researchers evaluated women aged 18 to 50 years with PCOS (n=124) and geographically matched controls (n=67). The patients with PCOSdemonstrated higher BMI and blood pressure, but similar HDL and LDL levels compared with controls, according to data.

The mean ApoA-I levels were lower and ApoB to ApoA-I ratio was greater among patients with PCOS compared with controls (P<.01), researchers wrote.

In addition, women with PCOS displayed an 11% decrease in normalized cholesterol efflux capacity compared with controls (P<.05). The cholesterolefflux capacity was correlated with BMI, ApoA-I, HDL and presence of metabolic syndrome, researchers wrote.

Multivariable regression model data indicated that PCOS was significantly associated with less cholesterol efflux (beta level, –0.05; 95% CI, –0.1 to –0.009).

After adjustments for age and BMI, PCOS was also significantly associated with an atherogenic profile, including an increase in large VLDL particles, size and small LDL particles (P<.01).

PCOS: Endocrine Society Issues New Guidelines.

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An Endocrine Society task force has developed new guidelines for the treatment of polycystic ovary syndrome (PCOS).

The guidelines published online October 24 in the Journal of Clinical Endocrinology & Metabolism, are aimed at helping physicians and patients understand a complex condition that often has diverse symptoms.

Task Force Chair Richard S. Legro, MD, professor in obstetrics and gynecology, Penn State University College of Medicine, Hershey, Pennsylvania, and colleagues developed the evidence-based guidelines, using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to rate the strength and quality of recommendations.

“The Society’s recommendations allow physicians to make the diagnosis [of PCOS] if clear symptoms are present without resorting to universal hormone tests or ultrasound screenings,” Dr. Legro said in a press release.

The guidelines advise that an adult woman be diagnosed with PCOS if she has at least 2 of the following symptoms: excess androgen, ovulatory dysfunction, or polycystic ovaries. In addition, any diagnosis of PCOS must rule out other androgen-excess disorders. Physicians should also screen patients for endometrial cancer, mood disorders, obstructive sleep apnea, diabetes, and cardiovascular disease.

Diagnosis of PCOS in adolescent girls should be based on clinical or biochemical signs of hyperandrogenism, after excluding other possible causes, in the presence of persistent oligomenorrhea, the task force advises. A PCOS diagnosis during perimenopause and menopause should be based on a documented, long-term history of oligomenorrhea and hyperandrogenism in reproductive years, the report advises. A finding of PCO morphology via ultrasound would also provide supportive evidence, although the authors note this is least likely in menopausal women. The guidelines recommend against routine ultrasound for endometrial thickness in women with PCOS.

In diagnosing and treating women with PCOS, physicians should look for terminal hair growth, acne, alopecia, acanthosis nigricans, and skin tags during physical examination, according to the new guidelines. The guidelines also recommend screening for ovulatory status using menstrual history.

The guidelines advise assessment of body mass index, waist circumference, blood pressure, and oral glucose tolerance. Overweight and obese patients with PCOS symptoms should be screened for obstructive sleep apnea. Adults and adolescents should be screened and treated for depression and anxiety.

The committee recommends treatment with hormonal contraceptives as the first-line therapy for menstrual abnormalities and hirsutism/acne. Exercise therapy is recommended to manage weight, alone or with a calorie-restricted diet.

The task force advises against the use of metformin as a first-line PCOS treatment, but metformin is recommended for women with PCOS and type 2 diabetes or impaired glucose tolerance who do not succeed with weight loss and exercise. Metformin is also recommended for women who cannot take hormonal contraceptives.

For infertility, the report recommends clomiphene citrate as a first-line treatment. For women undergoing in vitro fertilization, the guidelines recommend metformin as adjuvant therapy to prevent ovarian hyperstimulation.

 

 

BMI may be most vital determinant of basal metabolic rate in PCOS.

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The BMI of patients with polycystic ovary syndrome appeared to be the most important factor in basal metabolic rate, independent of the polycystic ovary syndrome phenotype and insulin resistance, according to Margareta D. Pisarska, MD, who presented the data at the conjoint meeting of the International Federation of Fertility Societies and the American Society for Reproductive Medicine.

“Based on our study — since we do think obesity does play a significant role — we believe it is important for endocrinologists to help counsel these women in a fashion similar to those who are obese by emphasizing that weight loss and lowering BMI are important,” Pisarska, director of the division of reproductive endocrinology and infertility; director of the Fertility and Reproductive Medicine Center at Cedars-Sinai Medical Center; associate professor at Cedars-Sinai Medical Center and the David Geffen School of Medicine at UCLA, told Endocrine Today.

 

The researchers conducted the case-control study examining the metabolic changes (ie, lean body mass, body fat mass, body fat percentage, skeletal muscle mass, BMI and basal metabolic rate) in 128 patients with PCOS (mean age, 28.1 years) and 72 eumenorrheic, non-hirsute controls (mean age, 32.9 years).

In terms of hormonal profile, patients with PCOS had greater testosterone, dehydroepiandrosterone sulfate (DHEA-sulfate), fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels compared with controls.

After controlling for age and BMI differences, there was no difference in body composition parameters between patients with PCOS and controls. There were no significant results regarding changes to the basal metabolic rate (P=.0162), lean body mass (P=.0153) or skeletal muscle mass (P=.0169), she said.

However, differences in fasting insulin and HOMA-IR remained significant. When looking at insulin resistance in women with PCOS as a potential factor affecting body composition and metabolic rates, there was also no difference between these groups.

“It is not necessarily PCOS; BMI and age are probably the more important determinants of basal metabolic rate, regardless of PCOS phenotype and insulin resistance,” Pisarska said.

BMI may be most vital determinant of basal metabolic rate in PCOS.

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The BMI of patients with polycystic ovary syndrome appeared to be the most important factor in basal metabolic rate, independent of the polycystic ovary syndrome phenotype and insulin resistance, according to Margareta D. Pisarska, MD, who presented the data at the conjoint meeting of the International Federation of Fertility Societies and the American Society for Reproductive Medicine.

“Based on our study — since we do think obesity does play a significant role — we believe it is important for endocrinologists to help counsel these women in a fashion similar to those who are obese by emphasizing that weight loss and lowering BMI are important,” Pisarska, director of the division of reproductive endocrinology and infertility; director of the Fertility and Reproductive Medicine Center at Cedars-Sinai Medical Center; associate professor at Cedars-Sinai Medical Center and the David Geffen School of Medicine at UCLA, told Endocrine Today.

The researchers conducted the case-control study examining the metabolic changes (ie, lean body mass, body fat mass, body fat percentage, skeletal muscle mass, BMI and basal metabolic rate) in 128 patients with PCOS (mean age, 28.1 years) and 72 eumenorrheic, non-hirsute controls (mean age, 32.9 years).

In terms of hormonal profile, patients with PCOS had greater testosterone, dehydroepiandrosterone sulfate (DHEA-sulfate), fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels compared with controls.

After controlling for age and BMI differences, there was no difference in body composition parameters between patients with PCOS and controls. There were no significant results regarding changes to the basal metabolic rate (P=.0162), lean body mass (P=.0153) or skeletal muscle mass (P=.0169), she said.

However, differences in fasting insulin and HOMA-IR remained significant. When looking at insulin resistance in women with PCOS as a potential factor affecting body composition and metabolic rates, there was also no difference between these groups.

“It is not necessarily PCOS; BMI and age are probably the more important determinants of basal metabolic rate, regardless of PCOS phenotype and insulin resistance,” Pisarska said.

Two-state solution’ proposed for renaming PCOS.

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New terminology is warranted for improved diagnosis and treatment of polycystic ovary syndrome phenotypes, according to researchers.

 “We would like to propose a nosological ‘two-state solution’ to the conflict. The endocrine syndrome of hyperandrogenism and chronic anovulation, eg, the National Institutes of Health (NIH) phenotype, should have a new name that acknowledges both its reproductive features as well as its long-term metabolic risks. The phenotypes diagnosed by ovarian morphology, eg, the remaining Rotterdam phenotypes, should continue to be known as PCOS,” wroteAndrea Dunaif, MD, vice chair for research in the department of medicine at Northwestern University Feinberg School of Medicine, and Bart Fauser, MD, of the department of reproductive medicine and gynecology at the University Medical Center in Utrecht, the Netherlands.

 

The researchers cited recommendations from the NIH Office for Disease Prevention’s Evidence-based Methodology Workshop on PCOS held last year, which suggested clarifying benefits and drawbacks from diagnostic criteria; causes, predictors and long-term consequences; and treatment and prevention strategies. They added that the syndrome is often overlooked outside of obstetrics and gynecology visits.

Currently, the diagnostic criteria for PCOS by the NIH include hyperandrogenism and chronic anovulation; Rotterdam includes two of the following: hyperandrogenism, chronic anovulation and polycystic ovaries. Finally, the Androgen Excess Society criteria state that PCOS is marked by hyperandrogenism plus ovarian dysfunction indicated by oligo/amenorrhea and/or polycystic ovaries, according to the researchers.

“Specifically, we want to ensure that this recommendation does not lead to Balkanization of the field, which will clearly undermine the broad interdisciplinary efforts required for meaningful scientific advances in our understanding of PCOS,” they wrote.

Source: Endocrine Today

10 Symptoms of Gluten Intolerance.

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More than 55 diseases have been linked to gluten, the protein found in wheat, rye, and barley. It’s estimated that 99% of the people who have either gluten intolerance or celiac disease are never diagnosed. It is also estimated that as much as 15% of the US population is gluten intolerant. Could you be one of them? If you have any of the following symptoms it could be a sign that you have gluten intolerance:


1.) Digestive issues such as gas, bloating, diarrhea and even constipation. I see the constipation particularly in children after eating gluten.

2.) Keratosis Pilaris, (also known as ‘chicken skin’ on the back of your arms). This tends be as a result of a fatty acid deficiency and vitamin A deficiency secondary to fat-malabsorption caused by gluten damaging the gut.

3.) Fatigue, brain fog or feeling tired after eating a meal that contains gluten.

4.) Diagnosis of an autoimmune disease such as Hashimoto’s thyroiditis, Rheumatoid arthritis, Ulcerative colitis, Lupus, Psoriasis, Scleroderma or Multiple sclerosis.

5.) Neurologic symptoms such as dizziness or feeling of being off balance.

6.) Hormone imbalances such as PMS, PCOS or unexplained infertility.

7.) Migraine headaches.

8.) Diagnosis of chronic fatigue or fibromyalgia. These diagnoses simply indicate your conventional doctor cannot pin point the cause of your fatigue or pain.

9.) Inflammation, swelling or pain in your joints such as fingers, knees or hips.

10.) Mood issues such as anxiety, depression, mood swings and ADD.

Source: Eat Local Grown

Spironolactone/metformin superior to either treatment alone for PCOS.

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Low-dose spironolactone and metformin combination therapy compared with either drug alone appeared to be an effective treatment for the management of polycystic ovary syndrome, according to results from an open-label, randomized study conducted in India.

“The key findings suggest superior efficacy (menstrual cyclicity, Ferriman–Gallwey [FG] score, serum total testosterone, insulin sensitivity and compliance) of low-dose spironolactone and metformin over either drug alone in the management of PCOS, without increasing the adverse event rate,”Mohd Ashraf Ganie, MD, of the department of endocrinology and metabolism at All India Institute of Medical Sciences in Ansari Nagar, New Delhi, India, and colleagues wrote.

Women who fell under the Androgen Excess-PCOS (AE-PCOS) 2006 criteria for PCOS were randomly assigned to one of three groups: metformin 1,000 mg per day (n=56), low-dose spironolactone 50 mg per day (n=51) or a combination of both drugs (n=62) for 6 months.

Before randomization, women were given dietary counseling (30 kcal/kg to 35 kcal/kg composed of 50% to 55% carbohydrates, 20% to 25% protein and 15% to 20% fat with high fiber content) besides lifestyle advice (ie, 25 to 35 minutes of brisk walking per day).

Menstrual cycle patterns, FG score, BMI, waist-hip ratio, blood pressure, luteinizing hormone, follicle-stimulating hormone, total testosterone, glucose and insulin sensitivity indices were measured at baseline, 3 and 6 months after the intervention. Data indicate all groups had comparable mean age and BMI at baseline.

At 6 months, menstrual cycles per year increased, whereas FG scores, serum total testosterone, AUC-glucose and AUC-insulin decreased significantly (P<.05) in the combination group compared with either therapy alone, according to data.

The adverse events associated with combination therapy were not significantly high. However, some of the clinical benefits could be the result of lifestyle modifications due to the lack of a placebo arm, researchers wrote. Yet, the efficacy and compliance were apparent without an increase in adverse events.

PERSPECTIVE

 

  • This study confirms what we have suspected for some time: that combination therapy is better for women with PCOS than single-agent treatment. In this case, combination therapy included an insulin sensitizer (metformin) and an androgen blocker (spironolactone). It is important to understand that combination therapy works best if the medications being used have differing mechanisms of action. For example, there are a number of drugs that decrease the production of androgens (i.e., metformin or oral contraceptives) while other drugs will block the action of androgens (i.e., spironolactone, finasteride, etc.). Medications may also improve metabolic function (e.g. metformin) if needed. In a disorder as complex and multifactorial as PCOS, optimum therapy will be one that combines currently available therapies to affect maximum benefit while minimizing side-effects. This study suggests that the combination of metformin 1000 mg and spironolactone 50 mg daily is one of these therapies.
  • Ricardo Azziz, MD
  • Professor of obstetrics and gynecology, medicine, and medical humanities
    President of Georgia Regents University
    CEO of Georgia Regents Health System

Source: Endocrine Today

 

Liraglutide-metformin combo superior to either treatment alone for weight loss in PCOS.

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Short-term combination liraglutide and metformin yielded significant weight loss among obese women with polycystic ovary syndrome,Mojca Jensterle Sever, MD, PhD, of the University Medical Center in Ljubljana, Slovenia, told Endocrine Today here at ENDO 2013.

“Obesity is a great problem in women with polycystic ovary syndrome (PCOS) and we do not have a conventional satisfactory treatment for it. The most widely used drug is metformin for women with PCOS and metabolic disturbances, but it’s somehow not successful enough to curb obesity. That’s why we tried to use our experience with diabetes to test long-acting GLP-1 agonists for any effect on the PCOS population,” Jenterle Sever said in an interview.

She and colleagues conducted a 12-week open, metformin-controlled trial by randomly assigning 36 obese women with PCOS aged 31.3 years (BMI 37.1 kg/m2) to one of the following treatment arms: metformin 1,000 mg twice daily (n=14), liraglutide (Victoza, Novo Nordisk) 1.2-mg administered daily subcutaneously (n=11) or combined therapy (n=11).

Jensterle Sever said that 38% of patients lost ≥5% body weight (22% in the combination group, 16% in the liraglutide group and zero in the metformin group). Patients assigned to combination therapy lost an average of 6.5 kg vs. 3.8 kg among those in the liraglutide group and 1.2 kg in the metformin group (P<.001), according to data.

Patients in the combination group also demonstrated a greater decrease in BMI and waist circumference compared with the other two treatment groups, according to data.

“We found that this combined arm was more successful in reducing weight, BMI and waist circumference as compared with liraglutide and metformin treatment arm alone.”

Adverse events included nausea during liraglutide treatment. However, this effect gradually declined over time and was not correlated with weight loss, Jensterle Sever said.

These findings suggest that short-term combined treatment of liraglutide and metformin led to statistically significant weight loss in obese women with PCOS. – by Samantha Costa

Source: Endocrine today