Clinical trial NCT02689843: Effects of Cyproterone Compound-spironolactone, Metformin and Pioglitazone on Inflammatory Markers in PCOS
Official title: Effects of Treatment With Cyproterone Compound-spironolactone, Metformin and Pioglitazone on Serum Inflammatory Markers in Patients With Polycystic Ovary Syndrome (PCOS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Polycystic Ovary Syndrome
Keywords: Inflammation
Complement system proteins
Homocysteine
C-Reactive Protein
Cyproterone
Ethinyl Estradiol
Androgen Antagonists
Metformin
Thiazolidinediones
Pioglitazone
Lead sponsor: Shiraz University of Medical Sciences
Sponsor class: OTHER
First posted: 2016-02-24
Enrollment: 90
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the effects of three-month course of treatment modalities (Cyproterone compound-Spironolactone, Metformin and Pioglitazone) in patients with polycystic ovary syndrome (PCOS) on markers of inflammation \[serum complement, homocysteine and high sensitive C-reactive protein (hs-CRP)\] levels.

Detailed description: Polycystic ovary syndrome (PCOS) is estimated to affect up to10% of women of reproductive age, making it one of the most common endocrine disorders in this population. PCOS is associated with a broad range of adverse sequel, including hypertension, dyslipidemia, insulin resistance, hyperandrogenaemia, gestational and type 2 diabetes,which ultimately increase the cardiovascular morbidity in these patients. Also PCOS is increasingly recognized as a component of the metabolic syndrome. Management depends on symptoms or the source of androgen excess. Several treatment options are available, which allows for an individualized approach. Spironolactone is the safest potent available antiandrogen. It is effective in lowering the hirsutism score by approximately one third, although considerable individual variations exist. Other antiandrogens used to treat hirsutism and hirsutism equivalents include cyproterone acetate that has weak antiglucocorticoid effects. Metformin and thiazolidinediones, are promising adjuncts for treating PCOS. Although both of them increase insulin sensitivity, but their mechanism of action differ.

Serum complement, homocysteine and C-reactive protein (CRP) levels have been reported to be linked with insulin resistance.

The investigators want to measure serum complement, homocysteine and hs-CRP levels in patients with PCOS before and after three-month course of treatment with Cyproterone compound-Spironolactone (CC-S), metformin (M) and pioglitazone (P).

Eligibility criteria: Inclusion Criteria:

* Age 18-35 years
* Diagnosis of Polycystic Ovary Syndrome (PCOS) according to Rotterdam criteria 2003 (two out of three required):

  1. Oligomenorrhea or anovulation
  2. Clinical and/or biochemical signs of hyperandrogenism
  3. Polycystic ovaries (by ultrasound)

Exclusion Criteria:

* Smoking
* Pregnancy
* Diabetes mellitus
* Renal failure (serum creatinine \>1.5)
* Congenital adrenal hyperplasia
* Hyper or hypothyroidism
* Sex hormone therapy or antiandrogen therapy during the last three months
* Unexplained serum alanin aminotransferase (ALT) elevation more than 2.5 times above normal range
* Any systemic or febrile illnesses
* Use of glucocorticoid or anti-inflammatory drugs during the last three months
* Androgen secreting tumor
* Malignancy

Primary outcomes:
measure: Serum C3 level
timeFrame: 3 months
measure: Serum C4 level
timeFrame: 3 months
measure: Serum high-sensitive CRP (C-reactive protein)
timeFrame: 3 months
Secondary outcomes:
measure: Serum total Testosterone level
timeFrame: 3 months
measure: Serum free Testosterone level
timeFrame: 3 months
measure: Serum Dehydroepiandrosterone sulfate (DHEAS) level
timeFrame: 3 months
measure: Serum follicle stimulating hormone (FSH) level
timeFrame: 3 months
measure: Serum luteinizing hormone (LH) level
timeFrame: 3 months
measure: Fasting Blood Sugar (FBS)
timeFrame: 3 months
measure: Fasting Serum Insulin level
timeFrame: 3 months
measure: Serum homocysteine level
timeFrame: 3 months
measure: Number of patients with adverse events
timeFrame: 3 months
Other outcomes:
Locations:
city: Shiraz
country: Iran, Islamic Republic of
facility: Shahid Motahhari Clinic, Shiraz University of Medical Sciences
state: Fars
Study officials:
affiliation: Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences
name: Mesbah Shams, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences
name: Gholamhossein R Omrani, MD
role: STUDY_CHAIR
References: