Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06015594 |
| Other study ID # |
PG/2020/12426 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2015 |
| Est. completion date |
May 1, 2022 |
Study information
| Verified date |
August 2023 |
| Source |
University of Cagliari |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This study aimed to understand whether metformin therapy can improve insulin resistance in
adolescent PCOS patients, both during treatment and after discontinuation, and to evaluate
its action on the hormonal and metabolic pathways.
Description:
Data were retrospectively retrieved from a database of clinical data collected in the
Outpatient Pediatric and Adolescent Gynecology Clinic of the University Hospital "Duilio
Casula," Monserrato, Cagliari (Division of Gynecology and Obstetrics, Department of Surgical
Sciences, University of Cagliari, Italy), between 2015 and 2019. PCOS diagnosis was adapted
for age following the 2019 update from Witchel SF and Carmina's recommendation.
The population consisted of 168 PCOS patients aged 12 to 17. Clinical examination, medical
history, blood sampling, and pelvic ultrasound (US) were performed. The number of
post-menarche years and the body mass index (BMI) were collected.
The patients were subjected to physical examination to evaluate hirsutism, according to the
criteria of the Ferriman and Gallwey score, as well as acne, using the Cremoncini
classification.
Each participant received detailed advice on improving their lifestyle, such as physical
activity and nutrition. Investigators gave indications of the various food and their weighted
intake and a balanced composition of macronutrients (carbohydrates 55%, lipids 25%, protein
20%; fiber ≥25 g/day), as recommended by the Reference intake levels of nutrients and energy
for the Italian population (LARN) guidelines. Vegetables, fruit, cereals, fish, and pulses,
typical of the Mediterranean style, were included in the diet.
Investigators recommended ≥150 minutes per week of moderate or ≥75 minutes of
vigorous-intensity exercise for weight gain prevention, minimizing sedentary time, and
including strength training exercises for two days per week, as reported from the 2018 PCOS
guideline.
Laboratory evaluations were performed during the menstrual cycle's first follicular phase
(days 3-7) and after a fast of 10-12 hours. Menstrual bleeding was induced by administering
medroxyprogesterone acetate (10 mg/day for five days) in amenorrhoeic patients.
Follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-β estradiol (E2), total
testosterone (TT), delta-4-androstenedione (A), 17-hydroxyprogesterone (17-OH-P) and sex
hormone binding globulin (SHBG) were tested. In addition, total cholesterol, HDL, LDL, and
triglycerides were measured with these blood tests.
The following day, the patients underwent a 75 g oral glucose tolerance test (OGTT). The OGTT
was performed at 9 am after fasting overnight. Blood samples were collected basally and 60,
90, 120, and 180 min after ingesting 75 g of glucose in 150 ml of water. Insulin and glucose
were assayed in all samples. Serum E2, FSH, LH, and TT were measured by chemiluminescence
immunoassay Immulite (Siemens Products Corporation, Los Angeles, CA). Enzymatic methods were
used for glucose, cholesterol, and triglycerides determination. Radioimmunoassay (RIA) was
used to measure serum A, insulin and 17-OHP (Diagnostic System Laboratories, Inc. [DSL],
Webster, TX). Insulin and glucose values were expressed as the area under the curve (AUC).
The AUC was calculated using the trapezoidal rule method and reported as mIU/ml times 180 min
for insulin.
A normal glycemic response to OGTT was defined according to the criteria of the National
Diabetes Data Group (1979).
As previously described, a normal insulinemic response to OGTT was defined by a threshold AUC
value of 16,900 mIU / ml / 180 min.
Insulin sensitivity evaluation was estimated using the homeostatic model assessment index
(HOMA), which was calculated as follows: HOMA = [fasting insulin (mU/ml) * fasting glucose
(mmol/l)/22, 5].
The same operator acquired ovarian morphology and ovarian volume for all patients. Ultrasound
was performed by a transabdominal probe in a whole bladder or transvaginally. A Voluson E6
ultrasound system equipped with a 2-8 MHz RAB4-8-D convex transducer (GE Medical Systems,
Austria) was used for the investigation. The ultrasound examination was performed on the same
day the blood samples were taken. Ovarian volume was calculated using the formula for a
modified prolate ellipsoid (longitudinal x transverse x anterior-posterior * 0.5233). The
mean volume values of both ovaries were included in the statistical analysis.
Participants were categorized into two groups: the study group, consisting of patients who
received metformin therapy, and the control group, which did not receive metformin during the
study period.
The metformin dose was determined based on the study by Fulghesu et al. Both the study and
control group underwent the same combined oral contraceptive pills (COCs), containing
drospirenone 3 mg/ethinyl estradiol 20 μg (3 mg DRSP/20 μg EE-24/4).
Follow-up was performed every 3-6 months in the first year, then after 12 months by OGTT and
clinical evaluation.
After about 24 months of treatment, the patients returned to the hospital and repeated
clinical and laboratory examinations. Finally, the patients repeated the same blood tests and
overall assessment at least 24 months after discontinuing metformin therapy. Baseline data
are expressed as b-AUC, b-HOMA, and b-BMI. End-of-therapy evaluation data are described as
e-AUC, e-HOMA, and e-BMI.
Evaluation data after the end of therapy are reported as ae-AUC, ae-HOMA, and ae-BMI.
Patient data were collected anonymously on an Excel® database (Office 365). Statistical
analysis was performed using the IBM SPSS Statistics statistical software, version 26 (IBM
SPSS Statistics, Chicago, IL, USA). Measurement data corresponding to the normal distribution
were expressed by mean ± SD, and the t-test was used for the paired samples (Student's
t-test). In addition, the count data were expressed as n (%), and the beta coefficient of
linear regression with a 95% confidence interval (95% CI) was reported for each analysis. In
all calculations, a p-value < 0.05 was considered significant.
