Nutritional and Metabolic Diseases

Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Skin and Connective Tissue Diseases

Obesity

Syndrome

Polycystic Ovary Syndrome

Hirsutism

Menstruation Disturbances

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Hair Diseases

Skin Diseases

Virilism

Micronutrients

All Drugs and Chemicals

Hematinics

Vitamins

Other Dietary Supplements

Inositol

Folic Acid

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

6 months treatment with myo-inositol 1500 gr

myo-inositol 1500 gr

myo-inositol 2000 gr + folic acid 200 mcg

Previous studies have demonstrated that Myo-inositol is capable of restoring spontaneous ovarian activity, and consequently fertility, in most patients with PCOS. The aim of our study is to investigate the role of folic acid conteined in the inositol preparation. The study group included 50 patients, randomly allocated to subgroup A (myo-inositol 1500 gr) and subgroup B (myo-inositol 2000 gr + folic acid 200 mcg). The investigation include menstrual pattern and hirsutism score evaluation, hormonal assays, oral glucose tolerance test, euglycemic hyperinsulinaemic clamp and lipide profile at baseline and after six months of treatment.

Combination Therapy With Myo-inositol and Folic Acid Versus Myo-inositol Alone

Combination Therapy With Myo-inositol and Folic Acid Versus Myo-inositol Alone: Effects of Six Months Treatment on Clinical, Endocrine and Metabolic Features in Obese Women With Polycystic Ovary Syndrome

We'll estimate the efficacy of the two treatments on the ovarian function and menstrual pattern.

Catholic University of the Sacred Heart

medical doctor

Adult women will be assigned to this category if they report a history of regular menstrual cycles. We will aim to recruit 120 women in this category.

Adult women will be assigned to this category if they report a history of irregular menstrual cycles, without a pre-existing diagnosis of PCOS. We will aim to recruit 120 women in this category.

Adult women will be assigned to this category if they report a history of irregular menstrual cycles with a pre-existing diagnosis of PCOS by a physician. We will aim to recruit 120 women in this category.

Marla E. Lujan, PhD

The investigators would like to determine how aspects of metabolism and age influence ovarian function. The purpose of the study is to understand how nutrition and metabolism relate to follicle development in women with regular cycles, irregular cycles, or polycystic ovary syndrome (PCOS). We also plan to identify lifestyle factors associated with PCOS and understand how diet and activity levels impact features of PCOS.

In the ovaries, eggs rest in fluid filled sacs called follicles. When follicles grow they form small fluid-filled cysts that can be easily seen when we use ultrasound to view the ovaries. In women with regular menstrual cycles, groups of follicles grow and regress 2 to 3 times during their cycle (usually over a 28- day period). Several of these follicles grow to a stage where they begin to develop the potential to ovulate - but in general only one follicle is chosen to ovulate. Thus, at any given time during the menstrual cycle, numerous fluid-filled follicles can be visualized in a woman's ovaries at various stages of development using transvaginal ultrasonography. In women with absent or infrequent menstrual cycles, very little is known about the growth patterns of their follicles and how factors such as metabolic hormones, might play a role in the failure to ovulate. Being underweight or overweight increases your chances of having irregular or absent menstrual cycles and a history of abnormal reproductive function compounds your risks for chronic diseases such as infertility, diabetes, hypertension, atherosclerosis and certain cancers. This is particularly the case for women with PCOS that have menstrual cycles that appear to worsen or improve depending on their body weight and metabolic status. Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 6-12% of reproductive-aged women within the general population. The hallmark features of PCOS are menstrual irregularity, increased levels of androgens, and polycystic ovaries. The current diagnostic criteria require 2 out of 3 of these features to be present for the diagnosis, therefore a number of phenotypes of PCOS exist. However, the metabolic and reproductive differences across the phenotypic spectrum of PCOS are not well understood. Women with PCOS characteristically have polycystic ovaries, where up to 10 times more follicles are present in the ovary at any given time. Further, the follicle-size populations and overall distribution throughout the ovary varies in women - follicles may be situated around the periphery of the ovary or may be distributed throughout the ovary. Presumably these small follicles are arrested in development - but emerging data from the Lujan laboratory suggest that this is not the case. Rather, follicles continue to grow in a dynamic pattern during these prolonged periods of anovulation. By comparing follicle populations, reproductive hormones and markers of metabolism in women with regular cycles, women with irregular cycles, and women with a history of PCOS, the researchers plan to identify what factors might explain why fertility potential and long-term health are compromised in some women but not in others. By including women at both early and late stages of their reproductive potential, the researchers will also be able to assess what influence age has on these factors. The ultimate goal of this research is to understand how nutrition and metabolism regulate follicle development in women so we can better develop lifestyle and drug therapies to help women preserve their fertility and long-term health. Since obesity has recently become the leading cause of infertility in North America, these studies are especially important.

Current research has failed to thoroughly examine the relationships between dietary intake, energy expenditure and PCOS. The purpose of this proposed study is to identify lifestyle factors associated with PCOS. Through dietary intake and energy expenditure data, the researchers plan to examine potential lifestyle differences between PCOS and healthy women, as well as between BMI classifications within women with PCOS. The Research Team will also be able to evaluate the diet quality according to the USDA Dietary Guidelines for Americans of all women included in the study. The Research Team is also interested in the relationships between biological markers and lifestyle endpoints in women with and without PCOS. Previous literature has shown there are biological marker differences between those with and without PCOS. By examining these relationships, researchers may further understand whether PCOS status is associated with lifestyle parameters.

To accomplish these objectives, the investigators plan to recruit 120 women with regular menstrual cycles and 240 women with irregular menstrual cycles, with or without PCOS (sub-grouped into 120 women with irregular menstrual cycles and 120 women with a history of PCOS). Their goal is to recruit an equal number of women in each group such that they are matched for age (18 - 48 years old) and body mass index (BMI; Normal weight = 18 - 24.9 kg/m2; Overweight = 25 - 29.9 kg/m2; Obese ≥ 30kg/m2). Women will be included in the PCOS sub-group if they have a confirmed PCOS diagnosis from their primary care provider. Ultrasound scans of the ovaries will be assessed for the total number, size, and distribution of follicles using both two- and three-dimensional imaging techniques. Participants will have blood samples collected determine serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, progesterone, anti-müllerian hormone (AMH), and inhibin B. The following metabolic parameters will be assessed: (1) 75-gram oral glucose tolerance test to characterize glucose and insulin dynamics at 0, 30, 60, 90, and 120 minutes post-glucose ingestion; (2) dual X-ray absorptiometry (DXA) scan to quantify body fat and lean muscle distribution; (3) vitals and anthropometry assessment to measure waist and hip circumference, height, weight, blood pressure, and heart rate, and (4) fasting blood tests to detect serum concentrations of androgens (i.e., total testosterone, androstenedione, free androgen index) and serum markers of metabolic syndrome (i.e., lipids and hemoglobin A1C). Participants will complete a food frequency questionnaire, a semi-structured dietary interview, and physical activity questionnaire. A researcher may also provide participants with an accelerometer to wear for a week. Participants may also elect to participate in an optional subcutaneous fat biopsy.

Nutritional and Metabolic Correlates of Ovarian Morphology in Women With Polycystic Ovary Syndrome

The number and size of all follicles in each ovary will be assess by ultrasonography for each participant with regular menstrual cycles, irregular menstrual cycles and PCOS.

Insulin sensitivity will be determined by administration of an oral glucose tolerance test and compared across groups.

The size of each ovary will be determined by ultrasonography for each participant and compared across groups.

Circulating AMH levels in the serum will be determined for each participant and compared across groups.

The ratio of circulating LH to FSH concentrations in the serum will be determined for each participant and compared across groups.

Total testosterone, androstenedione and free androgen index concentrations in serum will be determined and compared across groups.

Average menstrual cycle length as determined by self-reported history will be determined and compared across groups.

Degree of hirsutism as judged by the Ferriman-Gallwey scale will be determined and compared across groups.

Lipids, glucose and HbA1C concentrations will be determined and compared across groups.

Blood pressure will be determined and compared across groups.

The ratio of weight to height will be determined and compared across groups.

The ratio of waist circumference to hip circumference will be determined and compared across groups.

Percentage and distribution of fat and lean mass as assessed using DXA technology will be compared across groups.

A food frequency questionnaire will be administered to assess diet composition for the last three months

Participants will be asked to wear a small accelerometer device to assess physical activity

Subcutaneous fat biopsies will be conducted to assess differences in fat cell populations (major site of reproductive hormone synthesis) between groups

University of Rochester

Cornell University

Overweight

Overnutrition

Nutrition Disorders

Body Weight

Androgens

Women will be assigned to this category if they report a history of regular menstrual cycles (every 21 to 35 days). Recruitment will be targeted to obtain 20 lean (BMI\<25 kg/m2) and 20 overweight or obese (BMI\>24.9kg/m2) women in each of the following age groups: 18-24y (early), 25-34y (mid), ≥35y (later adulthood).

Women will be assigned to this category if they have clinical or biochemical androgen excess and report a history of irregular menstrual cycles (\<21 days or \>35 days), including women with a pre-existing diagnosis of PCOS. Recruitment will be targeted to obtain 20 lean (BMI\<25kg/m2) and 20 overweight or obese (BMI\>24.9kg/m2) women in each of the following age groups: 18-24y (early), 25-34y (mid), ≥35y (later adulthood).

Kathleen Hoeger, MD

The investigators would like to determine how aspects of adiposity and age influence ultrasound features of the ovaries which are used to diagnose polycystic ovarian syndrome (PCOS). The study will also compare anti-Müllerian hormone (AMH) levels against ultrasound features of the ovary to predict PCOS.

The purpose of this study is to develop ultrasound criteria for polycystic ovaries for women with PCOS across early, mid and late adulthood and to assess the impact of body composition on these ultrasound criteria.. The study will also compare ultrasound features of the ovary against or in combination with AMH (a hormonal biomarker) in predicting PCOS. This research will help improve the diagnosis of PCOS by considering multiple markers (i.e., ultrasound features and AMH levels) and multiple modifiers of those markers (i.e., age and adiposity).

As the name implies, the primary ultrasound feature used to diagnose PCOS is polycystic ovaries (PCO). However, PCO have frequently been observed in healthy women, calling into question the specificity of PCO to the condition of PCOS, as well as its ability to inform progression of the disease and/or response to treatment. The Lujan laboratory recently showed that the most widely accepted ultrasound criteria for PCO overlap with features of the normal ovary, and their laboratory proposed new thresholds to redefine PCO. These new criteria represented a significant change in the definition of PCO owing to the improved resolution of new technology. That said, these new criteria are still limited. They do not account for factors known or suspected to influence ovarian morphology. For example, follicle counts and ovarian size increase at puberty and decrease with age. Additional results from the Lujan laboratory showed that follicle number per ovary (FNPO) thresholds for women in later adulthood (35-38y) were substantially lower than those in early (18-25y) and mid-adulthood (26-34y). Furthermore, the new criteria for PCO do not account for a potential impact of adiposity on ovarian morphology. In the same study, conducted by the Lujan laboratory, overweight women exhibited more 6-9mm follicles than lean women, irrespective of androgen status.

Lastly, there is significant interest in determining whether AMH can serve as a surrogate to sonographic measures to define PCO. AMH is a peptide hormone produced by the granulosa cells of growing follicles and circulating levels represent secretions by antral follicles ≤8mm. Accordingly, serum AMH is increased in women with PCOS, reflecting the accumulation of 2-5mm antral follicles and greater production by granulosa cells of PCO compared to normal ovaries. Excess AMH is thought to inhibit follicle growth and selection. Unlike discrete aspects of ovarian morphology (i.e. follicle number or size),85 AMH levels remain largely constant throughout the normal menstrual cycle.Such stability may make AMH a more advantageous functional and surrogate morphological indicator of ovarian status compared to morphologic features. Further, some have argued that the variability in ultrasound assessments, and unsuitability of transvaginal approaches in certain clinical populations, justify the pursuit of a less onerous biomarker of PCO. However, there is significant bias across AMH assays and a consensual threshold for AMH to define PCO has not been determined. Proposed thresholds were hindered by heterogeneity in assay performance and in the clinical cohorts assessed. Ultimately, the ability of AMH to serve as a surrogate marker for PCO remains unknown and should be evaluated against sonographic measures in well-defined cohorts with improved assays. In this study, the researchers plan to refine the sonographic definition of PCO by establishing age-specific criteria that maintain sensitivity and specificity for PCOS in both lean and overweight populations. They will also clarify any ability of anti-Müllerian hormone (AMH) to better inform the diagnosis of PCOS.

To accomplish these objectives, the investigators plan to recruit 120 women with regular ovulatory cycles and 120 women with PCOS. Within each of these categories, the investigators plan to recruit 20 lean and 20 overweight women in each age group: 18-24y (early), 25-34y (mid), ≥35y (later adulthood). Ultrasound scans of the ovaries will be assessed for the total number, size, and distribution of follicles using both two- and three-dimensional imaging techniques. Additionally, participants will have blood samples collected to determine serum concentrations of AMH. Because features of the ovaries are expected to be different in lean and overweight women, the researchers hope to develop ultrasound criteria that will help healthcare providers to diagnosis specific ovulation problems in women across all body sizes and ages. This project addresses the need to improve methods and criteria used to define PCO across clinical populations.

Ovarian Ultrasonography for the Clinical Evaluation of Polycystic Ovary Syndrome

The number of follicles in each ovary will be assessed by ultrasonography

The number all follicles in a single cross sectional plane of each ovary will be assessed by ultrasonography

The brightness of the ovarian stroma in a single cross section will be determined by ultrasonography for each participant and compared across groups.

The ratio of the stromal area to the total ovarian area of the ovary in a single cross section will be determined by ultrasonography for each participant and compared across groups.

The follicle distribution pattern will be assessed by ultrasonography for each participant and compared across groups.

The ratio of circulating LH to FSH concentrations in the serum will be determined for each participant and compared across groups

Degree of hirsutism as judged by the Ferriman-Gallwey scale will be determined and compared across groups

Average menstrual cycle length as determined by self-reported history will be determined and compared across groups

Acne Vulgaris

Alopecia

Alopecia Areata

Plain, round, biconvex, white film-coated tablets that appear identical to MLE4901 tablets

Plain, round, biconvex, white film-coated tablets administered twice per day

For 80% of subjects randomized to MLE4901 (n=24/30), the dose is 40 mg twice daily. Six subjects (20%) randomized to higher MLE4901 dose cohorts that were promptly discontinued.

MLE4901

Placebo

This is a Phase 2b double-blind, randomized, parallel-group, placebo-controlled study of MLE4901 versus placebo in women with PCOS.

Following a Screening/Wash-out Period of up to 12 weeks, an 8-week Lead-in Period (starting with a progestin challenge) will be used to better characterize the study population. A Treatment Period of 28 weeks' duration will follow the Lead-in Period. Then, an 8-week Follow-up Period (i.e., no study drug) will be used to assess the durability of effects of MLE4901. The study duration will be approximately 48 weeks (11 months) per subject

MLE4901 vs. Placebo for the Treatment of PCOS

A Double-blind, Randomized, Parallel-group, Placebo-controlled Study of MLE4901 for the Treatment of Polycystic Ovary Syndrome (PCOS)

Assessment of the number of days between menstrual cycles (i.e., days between the start of a menstrual period and the start of the next consecutive menstrual period) from baseline to end of 28 week double blind treatment period

Number of menstrual periods from baseline to the end of the 28 week double blind treatment period

Medpace, Inc.

Covance

Millendo Therapeutics US, Inc.

Treatment with 1 matching placebo tablet self-administered twice daily

Placebo Treatment Arm

Treatment with 1 tablet of MLE4901 self-administered twice daily \[80% treated with dose of 40 mg twice daily\]

MLE4901 Treatment Arm

Matching placebo tablet self-administered twice daily

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Menstrual cycle frequency

Due to termination of the study by the Sponsor, no patients completed the study. No efficacy data are available because study termination occurred prior to scheduled assessments.

Director of Clinical Operations

Treatment with 1 tablet of study drug self-administered twice daily (most dosed with 40 mg BID)

The trial was terminated prior to collection of any efficacy data.

Menstrual Cycle Duration

Study terminated prior to collection of efficacy data.

Number of Menstrual Periods

Overall Study

Diseases and Abnormalities at or Before Birth

Rare Diseases

Hyperandrogenism

Disorders of Sex Development

46, XX Disorders of Sex Development

Congenital Abnormalities

Urogenital Abnormalities

Adrenal Hyperplasia, Congenital

Adrenogenital Syndrome

Male Urogenital Diseases

Congenital Adrenal Hyperplasia

21-hydroxylase Deficiency

Natriuretic Agents

Natriuretic Peptide, C-Type

30 patients with regular normal menstrual cycle

Serum level of CNP in PCOS and healthy women

C type natriuretic peptide

Özay

Recent studies have shown that C natriuretic peptide is produced from granulosa cells, increasing cumulative guanosine monophosphate (cGMP) production by affecting cumulus cells through natriuretic peptide receptors. It is suggested that produced cGMP maintains the transport of oocytes via the gap junctions and leads to a continuous increase in cyclic adenosine monophosphate (cAMP) levels in the oocyte. An important role of increased internal cAMP levels in the oocyte is shown to suppress meiotic progression.

Deoxyribonucleic acid studies in animals have shown that expression of the natriuretic peptide precursor increases during the periovulatory period and shows that this increase decreases rapidly after luteinizing hormone / human chorionic gonadotropin (hCG) stimulation.Human studies have shown that after ovulation induction, the CNP level in follicular fluid decreases following ovulatory dose of hCG.Polycystic ovary syndrome (PCOS) is the most common endocrine disease in the reproductive period, characterized by hyperandrogenism, oligo-anovulation, and polycystic ovarian morphology on ultrasonography, and in an animal study investigating the relationship between CNP and PCOS, serum CNP levels were increased in polycystic ovary syndrome.CNP serum level is thought to show differences between healthy women and women with polycystic ovary syndrome.

In this prospective study, a total of 60 patients are planed to be included. PCOS group will be consisted of 30 women and control group will include 30 healthy women with regular menstruation aged between 18-40 years old. PCOS diagnosis will be made according to Rotterdam criteria.

Age and body mass index of all participants will be recorded. BMI will be calculated by dividing weight by height in square meters. Then morning fasting venous blood samples will be taken from the patients between 2nd-5th day of menstruation for both groups. All blood samples will be centrifuged on the day of collection. Sera will be aliquoted into 1.5 mL Eppendorf (Eppendorf, Milano, Italy) tubes, and will be kept at -80°C until the day of CNP test. For the PCOS patients describing oligo/anovulation, after excluding pregnancy, progesterone withdrawal bleeding will be created and then the patients will be evaluated. Serum levels of LH, FSH, estradiol, thyroid stimulating hormone (TSH), prolactin (PRL), androstenedione, dehydroepiandrosterone sulfate (DHEAS), total testosterone, free testosterone, sex hormone binding globulin (SHBG), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), glucose and insulin levels will be analyzed. For insulin sensitivity, homeostatic model of insulin resistance (HOMA-IR) will be used and it will be calculated by the formula: HOMA-IR ¼ fasting blood glucose (mg/dL)fasting insulin (mIU/mL)/405. Free androgen index will be calculated by the formula 100x (Total testosteron/SHBG).

Serum CNP levels of the patients will be analyzed by an enzyme-linked immunosorbent (ELISA) assay for human C-type natriuretic peptide in accordance with the manufacturer's instructions (SEA721Hu, ELISA Kit for Human C-Type Natriuretic Peptide, Wuhan USCN Business Co., Ltd., Cloud-Clone Corp., CCC, USA).

Data will be analyzed using Statistical Packege for Social Sciences software (SPSS v15, SPSS Inc, Chicago, IL, USA). Independent t-test will be used to compare the parameters with normal distribution. Parameters that don't fulfill the parametric test assumptions will be compared using Mann-Whitney U test. Correlation of CNP with other parameters will be analyzed using Spearman's rank correlation test. Receiver operating characteristic (ROC) curve will be used to evaluate diagnostic sensitivity and specificity of CNP for PCOS. P values less than 0.05 will be regarded as statistically significant.

Comparison of Serum C Type Natriuretic Peptide Levels Between Polycystic Ovary Syndrome Patients and Healthy Women

C Type Natriuretic Peptide and Polycystic Ovary Syndrome

The comparison of serum levels of C type natriuretic peptide among PCOS and healthy women

We made a cut off value estimation for the diagnosis of PCOS by serum CNP levels using Receiver operator characteristics. The ROC curve incorporates both sensitivity (true positive rate) and specificity (true negative rate) providing a single assessment incorporating both measures. The higher the total area under the curve, the greater the predictive power of the CNP for diagnosing PCOS

Serum FSH and LH of PCOS and healthy women were compared

Serum Estradiol levels of PCOS and Healthy Women were compared

serum tiroid stimulating hormone of PCOS and healthy women were compared

serum prolactin levels of PCOS and healthy women were compared

Serum Androstenedione Levels of PCOS and Healthy Women were compared

Serum dehydroepiandrosterone sulfate (DHEAS) Levels of PCOS and Healthy Women were compared

Serum Total Testosterone Levels of PCOS and Healthy Women were compared

Serum Free Testosterone Levels of PCOS and Healthy Women were compared

Serum Sex Hormone Binding Globulin Levels of PCOS and Healthy Women were compared

Free androgen index of participants were compared. It was calculated with the formula 100XTotal testosterone/Sex hormone binding globulin

Serum glucose, total cholesterol and triglycerides levels of participants were compared

High density lipoprotein and low density lipoprotein levels of participants were compared

Serum Insulin Levels of Participants were compared

homeostatic model assessment of insulin resistance of participants were compared. The calculation was made with formula Glucose X Insulin/405.

Near East University, Turkey

Medical Doctor, assistant professor

36 patients with PCOS

C type natriuretic peptide: Serum level of CNP in PCOS and healthy women

Women With Polycystic Ovary Syndrome

30 patients with regular normal menstrual cycle

C type natriuretic peptide: Serum level of CNP in PCOS and healthy women

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination Therapy With Myo-inositol and Folic Acid Versus Myo-inositol Alone	NCT01555190	Polycystic Ovar... Hirsutism Menstrual Irreg...	myo-inositol 15... myo-inositol 20...	18 Years - 35 Years	Catholic University of the Sacred Heart
Combination Therapy With Myo-inositol and Folic Acid Versus Myo-inositol Alone	NCT01555190	Polycystic Ovar... Hirsutism Menstrual Irreg...	myo-inositol 15... myo-inositol 20...	18 Years - 35 Years	Catholic University of the Sacred Heart
Nutritional and Metabolic Correlates of Ovarian Morphology in Women With Polycystic Ovary Syndrome	NCT01927471	Polycystic Ovar... Menstrual Irreg...		18 Years - 48 Years	Cornell University
Ovarian Ultrasonography for the Clinical Evaluation of Polycystic Ovary Syndrome	NCT03547453	Polycystic Ovar... Menstrual Irreg... Overweight and ...		18 Years -	Cornell University
MLE4901 vs. Placebo for the Treatment of PCOS	NCT02865915	Polycystic Ovar...	MLE4901 Placebo	18 Years - 45 Years	Millendo Therapeutics, Inc.
Comparison of Serum C Type Natriuretic Peptide Levels Between Polycystic Ovary Syndrome Patients and Healthy Women	NCT04006171	Polycystic Ovar... c Type Natriure... Menstrual Irreg... Hyperandrogenis...	C type natriure...	18 Years - 40 Years	Near East University, Turkey
Comparison of Serum C Type Natriuretic Peptide Levels Between Polycystic Ovary Syndrome Patients and Healthy Women	NCT04006171	Polycystic Ovar... c Type Natriure... Menstrual Irreg... Hyperandrogenis...	C type natriure...	18 Years - 40 Years	Near East University, Turkey

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