Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Rare Diseases

Hemorrhage

Syndrome

Polycystic Ovary Syndrome

Hyperandrogenism

Anovulation

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

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

All Drugs and Chemicals

Androgens

Progesterone

Progestins

Hormones

Hormone Antagonists

Administration of 200 mg of vaginal Micronized Progesterone (100 mg every 12 hours) for a 7-day course

Anovulatory women with Polycystic ovary syndrome and clinical hyperandrogenism attended in our Hospital will participate in the study. A patient information sheet will be provided and written consent will be obtained. Patients who give written consent will participate in the trial. All patient information will be confidential and only be available to researches involved in the study.

Blood samples will be collected at baseline (Sample #1) and between the 3rd and the 5th day of withdrawal after 7 days of 100mg vaginal MP every 12 hours of administration(Sample#2).

Micronized Progesterone

Hormonal evaluation of women who are suspected of having Polycystic ovary syndrome (PCOS) involves the measurement of basal levels of androgens and 17-hydroxyprogesterone (17-OHP), which are generally used to establish the presence of hyperandrogenemia. In general, these levels are obtained during the follicular phase to maintain sampling uniformity and avoid spurious increases due to corpus luteum function. However, because most hyperandrogenic patients are oligo/amenorrheic, it is frequently necessary to administer a progestogen to induce withdrawal bleeding and properly time the blood sampling.

Several medications have been described to properly induce withdrawal bleeding , with medroxyprogesterone acetate (MPA) being the most widely use. However, synthetic compounds as MPA do not replicate precisely the constellation of biologic activities of the parent hormone and results in a temporary, albeit clinically relevant, suppression in ovarian function and circulating androgen levels , in addition of several adverse side effects .

In this study, it is hypothesized that the administration of natural progesterone vaginally, which will avoid hepatic first pass, may result in significantly less hormonal suppression.

The authors test this hypothesis by prospectively determining the effect of vaginal micronized progesterone (OMP), administered for the induction of withdrawal bleeding, on the circulating androgen and 17-OHP levels in women with PCOS.

Circulating Androgen Levels Are Not Affected by the Administration of Vaginal Micronized Progesterone for Withdrawal Bleeding in Patients With Polycystic Ovarian Syndrome

Difference between first and second sample in Total testosterone

Difference between first and second sample in free testosterone

Difference between first and second sample in sex hormone binding globulin (SHBG)

Difference between first and second sample in dehydroepiandrosterone sulfate (DHEAS)

Difference between first and second sample in androstenedione (A4)

Difference between first and second sample in 17-OH progesterone

Institut Universitari Dexeus

Fellow in Reproductive Endocrinology

Kennedy Disease

Reproductive Control Agents

Antineoplastic Agents

Estradiol

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Polyestradiol phosphate

Flutamide

Estrogens

Androgen Antagonists

Antineoplastic Agents, Hormonal

Prior to the first or second admission (randomly determined), subjects will be pretreated for 4 weeks with Flutamide (250 mg twice daily)

Prior to the first or the second admission (randomly determined), participants will be pretreated for 2 weeks with placebo (twice daily).

oral micronized progesterone suspension, 100 mg oral dose at 0800 during each study admission

Micronized progesterone

Placebo contains only inert ingredients and is not expected to exert any direct physiological effects.

Placebo

Flutamide, 250 mg taken orally twice daily for four weeks before study admission.

Two 0.1 mg/day transdermal estradiol patches will be applied 3 days prior to each inpatient admission; on the morning of study admission, these two patches will be removed and immediately replaced with two new 0.1 mg/day patches.

Estradiol patch

Melissa Gilrain, BS

Christopher M McCartney, MD

This study is trying to find out if flutamide (a medication that blocks the effects of testosterone) may help normalize an aspect of pituitary function (specifically, gonadotropin surge generation) in PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study. The investigators hypothesize that in estradiol-pretreated women with PCOS, acute progesterone augmentation of FSH release (positive feedback) will be enhanced by flutamide.

Women with PCOS appear to exhibit impaired progesterone (P4) augmentation of gonadotropin release (positive feedback), and this is at least partly independent of BMI differences. To test more directly the role of hyperandrogenemia/hyperandrogenism (HA), we will assess if the androgen-receptor blocker flutamide enhances P4 augmentation of gonadotropin release in estradiol (E2)-treated women with PCOS. We will study 10 women with PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study, with subjects undergoing two assessments of P4 positive feedback - once after 4 weeks' pretreatment with flutamide and once after 4-weeks' pretreatment with placebo (in random order). We will assess P4 positive feedback via frequent sampling for 16 hours. Subjects will be pretreated for 3 days (prior to CRU admission) with transdermal E2 (0.2 mg/day), starting no earlier than cycle day 7. Subjects will be admitted to the CRU the evening of day 3 of E2 treatment. Starting at 0200 h, blood will be collected for 16 hours. After 6 h of sampling (0800 h), subjects will receive a single oral dose of P4. A second CRU admission - performed at least 2 months later to permit adequate washout of flutamide (as needed) - will be identical to the first except that placebo pretreatment will be exchanged for flutamide pretreatment or vice versa. We will assess the P4-mediated augmentation of FSH release, with secondary endpoints including the P4-mediated augmentation of LH release. We hypothesize that in E2-pretreated women with PCOS, acute P4 augmentation of FSH release (positive feedback) will be enhanced by androgen-receptor blockade (flutamide).

Randomized, placebo-controlled, double-blinded, crossover study

This is a study regarding PCOS, so only females will be eligible

Androgen Blockade and Progesterone Augmentation of Gonadotropin Secretion

Ability of Androgen-receptor Blockade to Normalize Progesterone-induced Augmentation of Gonadotropin Secretion in PCOS (CRM010)

Change in mean FSH concentrations (post-progesterone FSH concentrations vs. pre-progesterone FSH concentrations)

Change in mean LH concentrations (post-progesterone LH concentrations vs. pre-progesterone LH concentrations)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Circulating Androgen Levels Are Not Affected by the Administration of Vaginal Micronized Progesterone for Withdrawal Bleeding in Patients With Polycystic Ovarian Syndrome	NCT03088046	Anovulation Polycystic Ovar... Hyperandrogenis...	Micronized Prog...	18 Years - 35 Years	Institut Universitari Dexeus
Androgen Blockade and Progesterone Augmentation of Gonadotropin Secretion	NCT04597099	PCOS Polycystic Ovar...	Micronized prog... Placebo Flutamide Estradiol patch	18 Years - 30 Years	University of Virginia
Circulating Androgen Levels Are Not Affected by the Administration of Vaginal Micronized Progesterone for Withdrawal Bleeding in Patients With Polycystic Ovarian Syndrome	NCT03088046	Anovulation Polycystic Ovar... Hyperandrogenis...	Micronized Prog...	18 Years - 35 Years	Institut Universitari Dexeus
Circulating Androgen Levels Are Not Affected by the Administration of Vaginal Micronized Progesterone for Withdrawal Bleeding in Patients With Polycystic Ovarian Syndrome	NCT03088046	Anovulation Polycystic Ovar... Hyperandrogenis...	Micronized Prog...	18 Years - 35 Years	Institut Universitari Dexeus

Spots Global Cancer Trial Database for micronized progesterone