PCOS
Conditions
Brief summary
The aim of the current work was to compare the efficacy of cavitation ultrasound, metformin or combination of both in obese women with polycystic ovary syndrome (PCOS) regarding clinical pregnancy rate, ovulation rate, insulin resistance, serum testosterone level, lipid profile.
Detailed description
Polycystic ovary syndrome (PCOS) affects 5 to 10% of women of childbearing age and is the most common cause of anovulatory infertility. Common clinical manifestations include menstrual irregularities and signs of androgen excess such as hirsutism, acne, and alopecia. Metformin, a biguanide, is the most widely used drug for the treatment of type 2 diabetes worldwide. Its primary action is to inhibit hepatic glucose production, but it also increases the sensitivity of peripheral tissues to insulin. The increase in insulin sensitivity, which contributes to the efficacy of metformin in the treatment of diabetes, has also been shown in non diabetic women with the polycystic ovary syndrome.In women with PCOS, long-term treatment with metformin may increase ovulation, improve menstrual cyclicity, and reduce serum androgen levels; the use of metformin may also improve hirsutism. If published data on the effects of metformin in the prevention of diabetes can be extrapolated to women with the PCOS, then the drug may actually retard progression to glucose intolerance in affected women, as reported in a small, retrospective study. Ultrasonic vibrations spread in the form of a wave in medium such as a liquid or a solid. When the particles of an elastic medium are under ultrasonic vibration, they act continuously in only one direction. The lipolytic range of ultrasounds is 30-70 Kilohertz (KHz), and the best effects are obtained in a range between30-35 KHz. The depth of the treatment in the tissues is generally2-3 cm, to avoid muscles involvement. Biological effects of ultrasounds on adipocytes are: micro-mechanical, thermal, micro-streaming and cavitation. Cavitation ultrasound means that ultrasounds produce an alternation of decompression and compression waves in a fluid media which progressively increase the tension of the adipocyte until it implodes and frees the emulsified fat. The aim of the current work was to compare the efficacy of cavitation ultrasound, metformin or combination of both in obese women with polycystic ovary syndrome (PCOS) regarding clinical pregnancy rate, ovulation rate, insulin resistance, serum testosterone level, lipid profile.
Interventions
DEVICECavitation US
The areas with localized fat are treated 2 times per week for 3 months using Aesthetic cavitation via ultrasonic cavitation machine (Cavi SMART, South Korea, supplied with one piece cavitation probe of 40 KHz, 3-6 watt(W)/cm\^2 adjustable, 60W with 20cm\^2 active surface).
DRUGMetformin
Metformin hydrochloride (Glucophage 500 mg/tablet, Bristol-Myers Squibb, New York, USA). Medication is initiated in a step-up fashion every 5 days, from one tablet per day to three. This dose is maintained as tolerated throughout the 3 months of the study.
OTHERCavitation US + Metformin
Combination of both Cavitation US + Metformin. the treatment duration lasts 3 months
Sponsors
Ain Shams University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Obese infertile polycystic ovarian syndrome (PCOS) women
Exclusion criteria
* Women 40 years or older * Women using fertility treatments, oral contraceptives or other confounding medications during the last 3 months * Smokers or with history of general diseases like cardiovascular, liver, kidney or respiratory disease, diabetes, uncontrolled hypertension, or malignancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinical Pregnancy Rate | 9 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ovulation Rate as Determined by Ultrasonographic Folliculometry and Luteal Serum Progesterone Assay. | 3 months | The Number of participants who had evidence of successful ovulation during the 3 months. Ovulation was diagnosed based on ultrasonographic folliculometry and/or luteal serum progesterone assay.Every month, folliculometry was done to count the number of antral follicles (AFC), follow follicular growth, measure dominant follicle diameter and detect occurrence of ovulation. a mid-luteal serum progesterone assay was done to confirm ovulation. Ultrasound was performed serially till reaching preovulatory follicle(s of around 20 mm in diameter that then rupture to show a collapsed follicle in the same location with internal echoes consistent with its transformation to a corpus luteum. Progesterone assay was done using immulite 2000 apparatus chemiluminescent immunometric assay. Mid-luteal phase progesterone above 6 ng/mL was considered indicative of normal corpus. luteum function. |
| Change in Insulin Resistance | Baseline and 3 months | Change in Fasting insulin concentration |
| Change in Serum Free Testosterone Level | Baseline and 3 months | Change in serum free testosterone levels |
| Change in Lipid Profile | Baseline and 3 months | Change in LDL levels was taken as the indicator of change in lipid profile |
Countries
Egypt
Participant flow
Recruitment details
252 women were assessed for eligibility 54 women were excluded * Not meeting inclusion criteria (n=38) * Declined to participate (n=9) * Other reasons (n=7)
Participants by arm
| Arm | Count |
|---|---|
| Cavitation US Cavitation ultrasound was done using ultrasonic cavitation machine 2 times per week for 3 months | 66 |
| Metformin Metformin oral tablets 500 mg were given three times daily for 3 months | 66 |
| Cavitation US + Metformin Combination of both Cavitation US + Metformin | 66 |
| Total | 198 |
Baseline characteristics
| Characteristic | Total | Cavitation US | Metformin | Cavitation US + Metformin |
|---|---|---|---|---|
| Abdominal fat mass | 6.9 Kilograms (kg) STANDARD_DEVIATION 2.6 | 6.8 Kilograms (kg) STANDARD_DEVIATION 2.8 | 6.9 Kilograms (kg) STANDARD_DEVIATION 3.2 | 7.1 Kilograms (kg) STANDARD_DEVIATION 2.2 |
| Acne No | 131 Participants | 48 Participants | 43 Participants | 40 Participants |
| Acne Yes | 67 Participants | 18 Participants | 23 Participants | 26 Participants |
| Age, Continuous | 26 Years STANDARD_DEVIATION 4.7 | 25.7 Years STANDARD_DEVIATION 4.5 | 26.1 Years STANDARD_DEVIATION 4.1 | 26.3 Years STANDARD_DEVIATION 5.2 |
| Androgenic alopecia No | 171 Participants | 54 Participants | 57 Participants | 60 Participants |
| Androgenic alopecia Yes | 27 Participants | 12 Participants | 9 Participants | 6 Participants |
| Body fat mass | 39.5 Kilograms (kg) STANDARD_DEVIATION 10.5 | 37.7 Kilograms (kg) STANDARD_DEVIATION 10.4 | 39.8 Kilograms (kg) STANDARD_DEVIATION 11.2 | 41.1 Kilograms (kg) STANDARD_DEVIATION 10.1 |
| Body hair mean score | 3.5 PCOSQ Body hair Score STANDARD_DEVIATION 1.7 | 3.4 PCOSQ Body hair Score STANDARD_DEVIATION 1.7 | 3.3 PCOSQ Body hair Score STANDARD_DEVIATION 1.9 | 3.7 PCOSQ Body hair Score STANDARD_DEVIATION 1.6 |
| Body Mass Index | 36.9 kg/m^2 STANDARD_DEVIATION 4.7 | 37.9 kg/m^2 STANDARD_DEVIATION 4.9 | 36.7 kg/m^2 STANDARD_DEVIATION 4.2 | 36.1 kg/m^2 STANDARD_DEVIATION 5.2 |
| Diastolic blood pressure | 81.7 millimeters of mercury (mmHg) STANDARD_DEVIATION 7.6 | 80.5 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.2 | 81.6 millimeters of mercury (mmHg) STANDARD_DEVIATION 7.1 | 82.9 millimeters of mercury (mmHg) STANDARD_DEVIATION 7.8 |
| Duration of infertility | 3.3 Years STANDARD_DEVIATION 1.4 | 3.3 Years STANDARD_DEVIATION 1.5 | 3.4 Years STANDARD_DEVIATION 1.3 | 3.2 Years STANDARD_DEVIATION 1.3 |
| Emotion mean score | 4.6 PCOSQ Emotion Score STANDARD_DEVIATION 1.6 | 4.3 PCOSQ Emotion Score STANDARD_DEVIATION 1.4 | 4.9 PCOSQ Emotion Score STANDARD_DEVIATION 1.6 | 4.7 PCOSQ Emotion Score STANDARD_DEVIATION 1.7 |
| Fasting glucose | 80.1 mg/dl STANDARD_DEVIATION 22.3 | 83.1 mg/dl STANDARD_DEVIATION 21.4 | 79.4 mg/dl STANDARD_DEVIATION 22.7 | 77.8 mg/dl STANDARD_DEVIATION 22.1 |
| Fasting Glucose/Insulin Ratio (GIR) | 6.46 mg/mIU STANDARD_DEVIATION 0.7 | 6.44 mg/mIU STANDARD_DEVIATION 0.8 | 6.35 mg/mIU STANDARD_DEVIATION 0.7 | 6.59 mg/mIU STANDARD_DEVIATION 0.7 |
| Fasting insulin | 12.4 µIU/ml STANDARD_DEVIATION 5.1 | 12.9 µIU/ml STANDARD_DEVIATION 6.4 | 12.5 µIU/ml STANDARD_DEVIATION 5.3 | 11.8 µIU/ml STANDARD_DEVIATION 4.1 |
| Fat free mass | 51.1 Kilograms (kg) STANDARD_DEVIATION 9.6 | 50.8 Kilograms (kg) STANDARD_DEVIATION 9.5 | 51.2 Kilograms (kg) STANDARD_DEVIATION 9.1 | 51.2 Kilograms (kg) STANDARD_DEVIATION 10.2 |
| Free testosterone | 3.8 pg/ml STANDARD_DEVIATION 1.71 | 3.9 pg/ml STANDARD_DEVIATION 2.07 | 3.8 pg/ml STANDARD_DEVIATION 1.32 | 3.7 pg/ml STANDARD_DEVIATION 1.72 |
| High-density lipoprotein (HDL) | 80.4 mg/dl STANDARD_DEVIATION 10.6 | 80.9 mg/dl STANDARD_DEVIATION 11.2 | 77.8 mg/dl STANDARD_DEVIATION 9.9 | 82.1 mg/dl STANDARD_DEVIATION 10.8 |
| Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | 2.46 HOMA score STANDARD_DEVIATION 1.01 | 2.65 HOMA score STANDARD_DEVIATION 1.01 | 2.45 HOMA score STANDARD_DEVIATION 1.06 | 2.27 HOMA score STANDARD_DEVIATION 0.99 |
| Infertility mean score | 3.6 PCOSQ Infertility Score STANDARD_DEVIATION 1 | 3.7 PCOSQ Infertility Score STANDARD_DEVIATION 1.02 | 3.6 PCOSQ Infertility Score STANDARD_DEVIATION 0.9 | 3.4 PCOSQ Infertility Score STANDARD_DEVIATION 1.1 |
| LH/FSH ratio | 1.77 Ratio STANDARD_DEVIATION 0.6 | 1.79 Ratio STANDARD_DEVIATION 0.7 | 1.85 Ratio STANDARD_DEVIATION 0.6 | 1.68 Ratio STANDARD_DEVIATION 0.6 |
| Low-density lipoprotein (LDL) | 126.5 mg/dl STANDARD_DEVIATION 19.6 | 129.7 mg/dl STANDARD_DEVIATION 19.3 | 127.1 mg/dl STANDARD_DEVIATION 20.4 | 122.6 mg/dl STANDARD_DEVIATION 19.1 |
| Luteinizing Hormone (LH) | 10.9 mIU/ml STANDARD_DEVIATION 1.3 | 10.9 mIU/ml STANDARD_DEVIATION 1.1 | 10.7 mIU/ml STANDARD_DEVIATION 1.1 | 11.1 mIU/ml STANDARD_DEVIATION 1.8 |
| Menstrual pattern Amenorrhea | 141 Participants | 43 Participants | 47 Participants | 51 Participants |
| Menstrual pattern Oligomenorrhea | 57 Participants | 23 Participants | 19 Participants | 15 Participants |
| Menstrual problems mean score | 3.7 PCOSQ Menstrual problems Score STANDARD_DEVIATION 1.1 | 3.6 PCOSQ Menstrual problems Score STANDARD_DEVIATION 1.1 | 3.7 PCOSQ Menstrual problems Score STANDARD_DEVIATION 1.1 | 3.9 PCOSQ Menstrual problems Score STANDARD_DEVIATION 1.1 |
| Quantitative Insulin sensitivity Check Index (QUICKI) | 0.33 Index STANDARD_DEVIATION 0.04 | 0.33 Index STANDARD_DEVIATION 0.03 | 0.33 Index STANDARD_DEVIATION 0.04 | 0.34 Index STANDARD_DEVIATION 0.04 |
| Region of Enrollment Egypt | 198 Participants | 66 Participants | 66 Participants | 66 Participants |
| Seborrheic dermatitis No | 99 Participants | 40 Participants | 32 Participants | 27 Participants |
| Seborrheic dermatitis Yes | 99 Participants | 26 Participants | 34 Participants | 39 Participants |
| Serum Follicle-stimulating Hormone (FSH) | 6.2 mIU/ml STANDARD_DEVIATION 2.1 | 6.1 mIU/ml STANDARD_DEVIATION 1.9 | 5.8 mIU/ml STANDARD_DEVIATION 2.2 | 6.6 mIU/ml STANDARD_DEVIATION 2.3 |
| Sex: Female, Male Female | 198 Participants | 66 Participants | 66 Participants | 66 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Systolic blood pressure | 122 millimeters of mercury (mmHg) STANDARD_DEVIATION 11.6 | 122.4 millimeters of mercury (mmHg) STANDARD_DEVIATION 10.1 | 121.9 millimeters of mercury (mmHg) STANDARD_DEVIATION 12.4 | 121.8 millimeters of mercury (mmHg) STANDARD_DEVIATION 12.3 |
| Total body fat percent | 44.6 Percentage STANDARD_DEVIATION 5.8 | 43.2 Percentage STANDARD_DEVIATION 5.6 | 44.9 Percentage STANDARD_DEVIATION 6.2 | 45.6 Percentage STANDARD_DEVIATION 5.7 |
| Total cholesterol | 277.2 mg/dl STANDARD_DEVIATION 30.7 | 282.3 mg/dl STANDARD_DEVIATION 32 | 273.4 mg/dl STANDARD_DEVIATION 29.2 | 276.8 mg/dl STANDARD_DEVIATION 30.5 |
| Total testosterone | 0.83 ng/ml STANDARD_DEVIATION 0.04 | 0.84 ng/ml STANDARD_DEVIATION 0.05 | 0.83 ng/ml STANDARD_DEVIATION 0.04 | 0.83 ng/ml STANDARD_DEVIATION 0.04 |
| Triglycerides (TGs) | 204.3 mg/dl STANDARD_DEVIATION 25.7 | 204.9 mg/dl STANDARD_DEVIATION 28.1 | 199.6 mg/dl STANDARD_DEVIATION 22.4 | 208.4 mg/dl STANDARD_DEVIATION 26.8 |
| Waist to Hip Ratio (WHR) | 0.89 Ratio STANDARD_DEVIATION 0.7 | 0.88 Ratio STANDARD_DEVIATION 0.7 | 0.89 Ratio STANDARD_DEVIATION 0.7 | 0.91 Ratio STANDARD_DEVIATION 0.8 |
| Weight mean score | 2.4 PCOSQ Weight Score STANDARD_DEVIATION 1.4 | 2.6 PCOSQ Weight Score STANDARD_DEVIATION 1.4 | 2.4 PCOSQ Weight Score STANDARD_DEVIATION 1.3 | 2.1 PCOSQ Weight Score STANDARD_DEVIATION 1.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 66 | 15 / 66 | 19 / 66 |
| serious Total, serious adverse events | 0 / 66 | 0 / 66 | 0 / 66 |
Outcome results
Primary
Clinical Pregnancy Rate
Time frame: 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cavitation US | Clinical Pregnancy Rate | 12 participants |
| Metformin | Clinical Pregnancy Rate | 5 participants |
| Cavitation US + Metformin | Clinical Pregnancy Rate | 16 participants |
Secondary
Change in Insulin Resistance
Change in Fasting insulin concentration
Time frame: Baseline and 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cavitation US | Change in Insulin Resistance | -2.4 uIU/ml |
| Metformin | Change in Insulin Resistance | -1.1 uIU/ml |
| Cavitation US + Metformin | Change in Insulin Resistance | -3.4 uIU/ml |
Secondary
Change in Lipid Profile
Change in LDL levels was taken as the indicator of change in lipid profile
Time frame: Baseline and 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cavitation US | Change in Lipid Profile | -10.2 mg/dl |
| Metformin | Change in Lipid Profile | -8.9 mg/dl |
| Cavitation US + Metformin | Change in Lipid Profile | -20.9 mg/dl |
Secondary
Change in Serum Free Testosterone Level
Change in serum free testosterone levels
Time frame: Baseline and 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cavitation US | Change in Serum Free Testosterone Level | -0.4 pg/ml |
| Metformin | Change in Serum Free Testosterone Level | -0.2 pg/ml |
| Cavitation US + Metformin | Change in Serum Free Testosterone Level | -0.6 pg/ml |
Secondary
Ovulation Rate as Determined by Ultrasonographic Folliculometry and Luteal Serum Progesterone Assay.
The Number of participants who had evidence of successful ovulation during the 3 months. Ovulation was diagnosed based on ultrasonographic folliculometry and/or luteal serum progesterone assay.Every month, folliculometry was done to count the number of antral follicles (AFC), follow follicular growth, measure dominant follicle diameter and detect occurrence of ovulation. a mid-luteal serum progesterone assay was done to confirm ovulation. Ultrasound was performed serially till reaching preovulatory follicle(s of around 20 mm in diameter that then rupture to show a collapsed follicle in the same location with internal echoes consistent with its transformation to a corpus luteum. Progesterone assay was done using immulite 2000 apparatus chemiluminescent immunometric assay. Mid-luteal phase progesterone above 6 ng/mL was considered indicative of normal corpus. luteum function.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cavitation US | Ovulation Rate as Determined by Ultrasonographic Folliculometry and Luteal Serum Progesterone Assay. | 39 participants |
| Metformin | Ovulation Rate as Determined by Ultrasonographic Folliculometry and Luteal Serum Progesterone Assay. | 16 participants |
| Cavitation US + Metformin | Ovulation Rate as Determined by Ultrasonographic Folliculometry and Luteal Serum Progesterone Assay. | 45 participants |