The Effect of Weight Loss on Anti-Müllerian Hormone Levels in Women With Polycystic Ovary Syndrome (PCOS)

Obesity Clinical Trial

Official title:

The Effect of Weight Loss With Orlistat or Sibutramine Administration , Hypocaloric Diet and Physical Exercise , on AMH Levels, in Women With Polycystic Ovary Syndrome

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01475019
• Other study ID #: A1732,2011
• Status: Active, not recruiting
• Phase: Phase 4
• First received: November 14, 2011
• Last updated: November 18, 2011
• Start date: January 2004
• Est. completion date: December 2012

Study information

• Verified date: November 2011
• Source: Aristotle University Of Thessaloniki
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: National Organization of Medicines
• Study type: Interventional

Clinical Trial Summary

The first aim of the investigators study, was to investigate the combined effect of diet,physical exercise and orlistat, for 24 weeks, on serum Anti-Müllerian Hormone (AMH) levels in obese women with polycystic ovary syndrome (PCOS) and in obese controls.

The other aim of the investigators study, was to examine the effect of hypocaloric diet,physical exercise plus sibutramine on serum AMH levels, body composition, hormonal and metabolic parameters in overweight and obese patients with polycystic ovary syndrome (PCOS).

Description:

The first aim of our study, was to investigate the combined effect of diet,physical exercise and orlistat, for 24 weeks, on serum Anti-Müllerian Hormone (AMH) levels in obese women with polycystic ovary syndrome (PCOS) and in obese controls.

The study included sixty one (61) women with PCOS (mean age: 26.11±6.86 and mean body mass index: 34.83±6.39), matched for age and body mass index (BMI) with twenty (20) obese women without PCOS (mean age: 26.95±4.77 and mean BMI: 36.79±6.98). Diagnosis of PCOS was based on the 2003 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus criteria.

Briefly, a moderate daily physical activity and a normal-protein, energy restricted diet were prescribed based on a calculated individual basal metabolic rate (BMR) of all women (BMR-600 kcal/d), for a period of 24 weeks. In addition, orlistat (Xenical, Roche S.A., Greece; 120 mg, 3 times per day) was administered before each meal, for 24 weeks. At baseline, week 12, and week 24, at 9:00 AM, after an overnight fast, subjects were weighed. Waist and hip circumferences were measured in duplicate. Blood samples were collected and the basal serum levels of AMH, FSH, LH, PRL, T, D4A, DHEAS, 17a-hydroxyprogesterone (17a-OHP), SHBG, glucose, and insulin were measured. AMH concentrations were measured with an enzymatically amplified two-sided immunoassay [DSL-10-14400 Active Müllerian Inhibiting Substance/AMH enzyme-linked immunosorbent assay (ELISA) kit, DSL Laboratories, Webster, TX]. The theoretical sensitivity of the method is 0.006 ng/ml, the intra-assay coefficient of variation for high values is 3.3% and the interassay coefficient of variation for high values is 6.7%.

We also studied the changes of mean number of follicles (expressed as the mean number of follicles of both ovaries= follicles of right ovary+ follicles of left ovary/2) and mean ovarian volume (expressed as the mean volume of both ovaries= volume of right ovary+ volume of left ovary/2).

The other aim of our study, was to examine the effect of hypocaloric diet,physical exercise plus sibutramine on serum AMH levels, body composition, hormonal and metabolic parameters in overweight and obese patients with polycystic ovary syndrome (PCOS).

Outpatients, premenopausal, nonpregnant, nonlactating, overweight and obese women (body mass index, BMI >27), 18 years of age and older with PCOS were recruited for this study. The study included fifty seven (57) women with PCOS (mean age: 26.11±6.86 and mean body mass index: 34.83±6.39) who, besides diet and exercise, received Sibutramine treatment, matched for age and body mass index (BMI) with nineteen (19) obese women with PCOS (mean age: 26.95±4.77 and mean BMI: 36.79±6.98) treated only with diet and exercise. Diagnosis of PCOS was based on the 2003 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus criteria . Women with no classical 21-hydroxylase deficiency, hyperprolactinemia, adrenal or ovarian tumor and Cushing's disease were excluded by the appropriate tests. Other exclusion criteria were hypertension, thyroid dysfunction, overt diabetes mellitus and concomitant treatment, such as antihypertensive drugs, selective serotonin reuptake inhibitor or other SNRI drug, oral contraceptive pills or any other antiandrogen treatment (cyproterone acetate, spirolactone, luteinizing hormone (LH) release hormone agonist) and insulin-sensitizing agents (metformin, pioglitazone, rosiglitazone) that may interact with insulin sensitivity and lipid profile.

Briefly, all patients were placed in a hypocaloric diet plus sibutramine (10mg per day) for the first month and then on a hypocaloric diet plus sibutramine (10mg per day) or hypocaloric diet only for the subsequent 6 months. A moderate physical activity (3 hours per week) and a normal-protein, energy restricted diet were prescribed based on a calculated individual basal metabolic rate (BMR) of all women (BMR-600 kcal/d), for a period of 24 weeks.

At baseline, week 12, and week 24, at 9:00 AM, after an overnight fast, subjects were weighed. Waist and hip circumferences were measured in duplicate. Blood samples were collected and the basal serum levels of AMH, FSH, LH, PRL, T, D4A, DHEAS, 17a-hydroxyprogesterone (17a-OHP), SHBG, glucose, and insulin were measured. AMH concentrations were measured with an enzymatically amplified two-sided immunoassay [DSL-10-14400 Active Müllerian Inhibiting Substance/AMH enzyme-linked immunosorbent assay (ELISA) kit, DSL Laboratories, Webster, TX].

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: December 2012
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 39 Years

Eligibility

Inclusion Criteria:

• premenopausal,

• nonpregnant,

• nonlactating,

• overweight and obese women

Exclusion Criteria:

• classical 21-hydroxylase deficiency,

• hyperprolactinemia,

• adrenal or ovarian tumor and Cushing's disease

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Obesity
• Polycystic Ovaries Syndrome
• Polycystic Ovary Syndrome
• Syndrome

Intervention

Drug:
• Orlistat
Tablet, 120 mg, three times daily, for six months
• Sibutramine
Tablet, 10 mg, once daily, for six months

Behavioral:
• Diet and physical exercise
Hypocaloric diet and regular physical exercise

Locations

Country	Name	City	State
Greece	Aristotle University of Thessaloniki Medical School	Thessaloniki

Sponsors (1)

Lead Sponsor	Collaborator
Aristotle University Of Thessaloniki

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anti- Mullerian hormone (AMH) levels		6 months	No
Secondary	Weight loss		6 months	No
Secondary	Androgen levels	Free androgen index, Testosterone, 17OH Progesterone, D4 Andostenedione, Testosterone to Androstenedione ratio	6 months	No
Secondary	Follicular number	Mean follicular number	6 months	No
Secondary	Gonadotrophins	Follicular Stimulating Hormone (FSH), Luteneizing Hormone (LH), LH to FSH ratio	6 months	No