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

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.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome; Hyperandrogenism; Anovulation
• Intervention / Treatment: Drug: Micronized Progesterone

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Chronic ovulatory dysfunction, defined as intermenstrual intervals of >45 days or a total of <8 menstrual cycles per year
• Polycystic ovaries, defined as at least one ovary with >12 follicles between 2 and 9 mm or an ovarian volume >10 mL
• Clinical hyperandrogenism, defined by a Ferriman Gallwey score >8

Exclusion Criteria:

• non-classic congenital adrenal hyperplasia,
• hyperprolactinemia
• thyroid dysfunction
• Oral contraceptives pills taken at least 3 months before the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Drug: Micronized Progesterone; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total testosterone (TT)	Difference between first and second sample in Total testosterone	Blood samples will be collected at baseline (Sample #1) , and between the 3rd ad the 5th day of withdrawal after the treatment (sample #2)
Change in free testosterone (FT)	Difference between first and second sample in free testosterone	Blood samples will be collected at baseline (Sample #1) , and between the 3rd ad the 5th day of withdrawal after the treatment (sample #2)
Change in sex hormone binding globulin (SHBG)	Difference between first and second sample in sex hormone binding globulin (SHBG)	Blood samples will be collected at baseline (Sample #1) , and between the 3rd ad the 5th day of withdrawal after the treatment (sample #2)
Change in dehydroepiandrosterone sulfate (DHEAS)	Difference between first and second sample in dehydroepiandrosterone sulfate (DHEAS)	Blood samples will be collected at baseline (Sample #1) , and between the 3rd ad the 5th day of withdrawal after the treatment (sample #2)
Change in androstenedione (A4)	Difference between first and second sample in androstenedione (A4)	BBlood samples will be collected at baseline (Sample #1) , and between the 3rd ad the 5th day of withdrawal after the treatment (sample #2)
Change in 17-OH progesterone	Difference between first and second sample in 17-OH progesterone	Blood samples will be collected at baseline (Sample #1) , and between the 3rd ad the 5th day of withdrawal after the treatment (sample #2)

Collaborators and Investigators

• Sponsor: Institut Universitari Dexeus

Publications and helpful links

General Publications

• Livadas S, Boutzios G, Economou F, Alexandraki K, Xyrafis X, Christou M, Zerva A, Karachalios A, Tantalaki E, Diamanti-Kandarakis E. The effect of oral micronized progesterone on hormonal and metabolic parameters in anovulatory patients with polycystic ovary syndrome. Fertil Steril. 2010 Jun;94(1):242-6. doi: 10.1016/j.fertnstert.2009.02.073. Epub 2009 May 5.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2014
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: March 1, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (ACTUAL): March 23, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 23, 2017
• Last Update Submitted That Met QC Criteria: March 16, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; 46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Adrenogenital Syndrome; Congenital Abnormalities; Polycystic Ovary Syndrome; Hyperandrogenism; Syndrome; Anovulation; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: SMD-2017-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No