Trial Information

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

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].