What are the effects of a 16-week exercise program on ovarian function in women with morbid obesity who have undergone bariatric surgery?

Plasma level of sex hormone binding globulin (SHBG) at baseline and 16-week and 1-year follow-up measured by immunoassay with a Beckman Coulter kit, with a maximum value of 200 nmol/l and an imprecision of less than 7%

All outcomes will be assessed at baseline, as well as at follow-up (i.e. week 16 and 1 year)

Secondary outcomes related to ovarian function (primary aim):
1. Plasma level of anti-Müllerian hormone (AMH) measured using an ELISA assay (antimüllerian hormone Gen II ELISA assay; Beckman Coulter, Brea, CA, USA), with a detection limit of 17 pmol/l, and with a coefficient of variation of less than 10%
2. Plasma level of follicle-stimulating hormone (FSH), as a marker of ovulatory capacity, measured using the Beckman Coulter immunoassay kit, with a sensitivity of 0.2 mIU/ml, with an imprecision of less than 10%
3. Plasma level of thyroxine (T4; ng/dl) measured in the laboratory using a Beckman Coulter immunoassay kit
4. Plasma level of thyrotropin (TSH; μIU/l), as a marker of thyroid function, measured in the laboratory using a Beckman Coulter immunoassay kit, with a detection limit of 100 mUI/l and a coefficient of variation of 0.003 µUI/ml
5. Plasma level of luteinizing hormone (LH; mUI / l) measured using a Beckman Coulter immunoassay kit, with a detection limit of 250 IU/l with a coefficient of variation of 0.2 mIU/ml
6. Plasma level of estradiol (pmol/l) measured in the laboratory using Beckman Coulter immunoassay kit
7. Plasma level of prolactin (ng/ml) measured using a Beckman Coulter immunoassay kit
8. Plasma level of total testosterone (ng/ml) measured using a Beckman Coulter immunoassay kit, with a detection limit of 16 ng/ml with a coefficient of variation of 0.1 ng/ml
9. Free androgenic index will be calculated as the total testosterone:SHBG ratio

Outcomes obtained by transvaginal ultrasound using the Toshiba Xario ultrasound equipment (Toshiba Medical Systems Corporation, Japan) equipped with a 7 MHz curved endovaginal transducer.
10. Ovocitary count. The total number of follicles whose size is between 2 and 8 mm ultrasound visualized in both ovaries will be recorded.
11. Diameters of both ovaries measured sonographically in the longitudinal axis and in the transverse axis (mm)
12. Endometrial thickness: measurement of the thickness of the endometrium ultrasound visualized in a longitudinal section of the uterus.
13. Pulsatility index of uterine arteries (left, right and middle), measured by ultrasound. The 7 MHz endovaginal transducer must be placed paramedially to the uterine cervix at the level of the internal cervical orifice. The vessel must be identified with color Doppler and high speed scales (between 30 and 50 cm/s) should be used for the selective identification of the vessel. The soundproofing angle for measurements must be less than 45°. Three or more waves of similar characteristics must be obtained for measurement, with adequate magnification, occupying at least three quarters of the screen. The size of the Doppler sample should be equivalent to the diameter of the artery and should be placed in the center of the vessel. The pulsatility index (PI) will be calculated.

Other variables relevant to to ovarian function:
14. Duration of menstrual bleeding (days) recorded by the gynecologist through personal interview with the participant
15. Duration of the menstrual cycle (days) recorded by the gynecologist through personal interview with the participant
16. Hirsutism measured using the Ferriman and Gallwey Scale. The score will be: ≤8: normal; 9-11: mild hirsutism; 12-9: moderate hirsutism; ≥20: severe hirsutism

Secondary outcomes related to secondary aims (i.e. markers of chronic inflammation and insulin resistance) obtained in plasma:
17. C-reactive Protein (CRP) levels (mg/l), as a relevant indicator of systemic inflammation, measured using an immunoturbidimetric analysis with the Beckman Coulter kit, with a detection limit of 80 mg/l with a coefficient of variation <1 mg/l
18. Interleukin 6 (IL-6; pg/ml) measured using a Cobas immunoassay kit, with a sensitivity of 1.5 pg/ml
19. Tumor necrosis factor alpha (TNFα; pg/ml) measured using a Cobas immunoassay kit, with a coefficient of variation of less than 8%
20. Leptin (pg/ml) measured using a Cobas immunoassay kit, with a coefficient of variation of less than 6%
21. Glomerular sedimentation rate (VSG, mm/h). It will be measured by Menarini diagnostics kit
22. Glucose and insulin measured using standard techniques. The HOMA index (homeostasis model assessment of insulin resistance) will be calculated using the formula [insulin, mIU/l] × [glucose, mg/dl])/405. Insulin is measured using the Cobas immunoassay kit, with an upper limit of 300 µUI/ml with a coefficient of variation of 0.03 µIU/ml.

Other secondary outcomes:
23. Arterial stiffness measured through pulse wave velocity (VOP; Mobil-O-Graph® 24-h pulse wave analysis monitor, IEM GmbH, Stolberg, Germany). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) will be measured with the same device and the mean blood pressure will be calculated as MBP =1/3(SBP - DBP) + DBP.
24. Body composition assessed by dual x-ray absorptiometry (DEXA; DMS Imaging, STRATOS dR). The percentage of total body fat, fat free mass and muscle mass will be measured.
25.Weight measured using an InBody270 body composition analyzer
26. Height measured using a Seca 22 stadiometer
27. Aerobic capacity (or cardiorespiratory fitness) assessed with the Bruce protocol on a treadmill
28. Lower limb muscular strength assessed with the 30-s chair stand test
29. Upper limb muscular strength assessed using handgrip dynamometry (i.e. handgrip strength test)
30. Range of motion of the shoulder girdle assessed using the back-scratch test
31. Health-related quality of life assessed with the 36-item Short Form Health Survey (SF-36) questionnaire. The score in its 8 dimensions and a physical and mental component summary (i.e. the score ranges from 0 to 100, with higher values representing a better quality of life) will be calculated.

Other information that will be registered:
32. Physical activity and sedentary time assessed using an ActiGraph activity monitor with ActiLife software version 6.11.7
33. Food intake assessed (at pre-test, post-test and 12-month follow-up) using two 24-h reminders
34. Frequency of food consumption assessed with the self-administered questionnaire used in the PREDIMED study
35. Adherence to the Mediterranean diet will be assessed with the PREDIMED questionnaire
36. Sociodemographic variables and clinical history: Age, marital status, level of education, employment status, income level, etc. will be recorded.
37. Personal history of obesity (duration of obesity), cardiovascular disease, hypertension, obstructive sleep apnea (OSA), type 2 diabetes, medication use, etc., assessed using the patient's medical history
38. Surgical technique assessed using patient's medical record. The surgical techniques to be performed are mini-gastric bypass with a single anastomosis (mainly), as well as laparoscopic sleeve gastrectomy (only when BMI ≥50).