Androgen Responses to hCG and Ovarian Morphology in PCOS

NCT03489668 | Unknown

• 1 other identifier: PoznanUMS6
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale and Hypothesis We have previously reported that theca cells (TC) responses to hCG in women with PCOS represent a spectrum where some exhibit exaggerated increases of 17OHP while in others 17OHP responses resemble those of normal women (Maas KH et al, JCEM, 2015). The basis for this differential responsiveness is not clear. Earlier studies reported that 17OHP responses to gonadotropin stimulation were heterogeneous among PCOS women, which was attributed to the degree of hyperinsulinemia (Pasquali R et al, JCEM, 2007). However, assessment of the ovary was omitted in the analysis. In preliminary studies, we have found that in women with PCOS, insulin sensitivity was strongly correlated with insulin sensitivity index as assessed by the method of Matsuda and DeFronzo (Diabetes Care, 1999). However, the study lacked sufficient numbers. Further analysis of insulin sensitivity with respect to hCG stimulated theca cell responses is warranted. We have also examined 17OHP responses to hCG in relationship to antral follicle count and anti-Müllerian hormone (AMH) in PCOS and normal women. In PCOS women, as expected, serum AMH correlated with antral follicle count. However, TC responses in PCOS were inversely related to AMH (Maas KH et al, JCEM, 2015). These novel observations suggested that in PCOS AMH production may reflect redistribution of the follicle population. In human ovaries maximal immunodetection of AMH is observed in small (\< 4 mm) antral follicles followed by a rapid and progressive decline until an absence of the protein by 8 mm (Weenen C et al, Mol Hum Reprod, 2004). This consideration raises the issue of whether normal AMH levels represent more advanced follicle growth in some PCOS women compared with that of others with elevated AMH levels. An increased stage of follicle development would be accompanied by increased TC hyperplasia and may account for greater 17OHP responses to hCG stimulation. A comparison of TC responses to hCG with ovarian morphology has not be done in women with PCOS. Based on these findings, we hypothesize that in PCOS, heterogeneous TC responses to hCG reflect differences in morphometric development of the follicle population. In addition, the positive correlation between insulin sensitivity and TC responses to hCG suggest an effect of hyperinsulinemia. We propose to investigate the relationship between theca cell responses to hCG, follicle morphology, and insulin sensitivity before and following treatment with an insulin lowering drug, metformin.

Conditions

PCOS

Keywords

PCOS; Androgen; 3D ultrasound

Outcome Measures

Primary Outcomes (1)

• 17-OHP responses to hCG in PCOS and normal women

  Demonstrating a relationship between theca cell responses to hCG, and insulin sensitivity before and following treatment with an insulin lowering drug, metformin.

  2 years

Secondary Outcomes (1)

• Ovarian morphology in PCOS and normal women

  2 years

Study Arms (2)

PCOS

ACTIVE COMPARATOR

Metformin administration 1500mg/day

Drug: MetFORMIN 500 Mg Oral Tablet

Control

NO INTERVENTION

Interventions

MetFORMIN 500 Mg Oral Tablet DRUG

metformin administration 1500mg per day

PCOS

Eligibility Criteria

• Age: 18 Years - 37 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \<8 spontaneous menses per year • hyperandrogenism clinically (Ferriman-Gallway score≥8 or total testosterone\>0.5ng/ml).

You may not qualify if:

• CAH, hyperprolactinemia, thyroid disorder, Cushings syndrome, hypothalamic anovulation

Sponsors & Collaborators

• Poznan University of Medical Sciences: lead
• University of California, San Diego: collaborator

Study Sites (1)

Division of Infertility and Reproductive Endocrinology, Department of Gynecology and Obsterics

Poznan, Poland

RECRUITING

MeSH Terms

Interventions

Metformin; Tablets

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

Beata E Banaszewska, MD PhD

CONTACT

+48501303173; bbeata48@gmail.com

Antoni Duleba, Prof

CONTACT

antoni.duleba@yale.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD Asssociate Professor

Study Record Dates

• First Submitted: March 29, 2018
• First Posted: April 5, 2018
• Study Start: January 20, 2018
• Primary Completion: January 31, 2020
• Study Completion: March 31, 2020
• Last Updated: August 9, 2018

Record last verified: 2018-08

Locations

PL (1)