Patient description: A 35-year-old woman presents with history of acne and mild hirsutism. The primary evaluation revealed elevated testosterone levels. She recently noticed gradual enlargement of her hands and feet and recognized that her ring is getting small for her finger. There is some irregularity in her menstrual cycle as well as some nipple discharge. She also has positive history for snoring and headache. The physical examination revealed subtle facial features of acromegaly and prognathism. Visual fields are normal by confrontation. Hirsutism, soft tissue thickening and diaphoresis of the hands and feet are noted. Laboratory evaluation in the fasting state reveals IGF-1 of 968 ng/mL and random GH of 19.7 ng/mL. MRI reveals a macroadenoma with no invasion. She is on stable doses of octreotide LAR since her diagnosis was confirmed. She is married and has 2 children. She is using IUD as her contraceptive method.

Clinical trial eligibility criteria: eligible ages (years): 18.0-40.0,  Polycystic Ovary Syndrome Insulin Resistance Hyperandrogenism women with PCOS: 1. Age 18 to 40 years 2. Body mass index (BMI) ≥25 to ≤40 given that 95% of all women with PCOS with a BMI ≥25 are insulin resistant (71,72). 3. PCOS diagnosis according to Rotterdam 2003 (73), with at least two of the following three symptoms: Clinical signs of hyperandrogenism (hirsutism or acne); oligo/amenorrhea; and/or polycystic ovaries (PCOS). Hirsutism is defined as a self-reported Ferriman-Gallwey (FG) score ≥8 (≥5 Asian) (74,75). Acne is defined by a positive response to the question Do you have acne? Oligomenorrhea is defined as an intermenstrual interval >35 days and <8 menstrual bleedings in the past year. Amenorrhea as <3 cycles per year. PCO is defined by transvaginal ultrasound with ≥12 follicles 2-9 mm and/or ovarian volume ≥10 ml in one or both ovaries. 4. Willing to sign the consent form controls: Controls should have BMI >25 to <40, regular cycles with 28 days ± 2 days, and no signs of hyperandrogenism. They are excluded if they have menstrual irregularities, signs of hyperandrogenism (FG >4), or evidence of PCO morphology on ultrasound  for all women 1. Age >40 2. of other endocrine disorders such as non-classic congenital adrenal hyperplasia (17-hydroxyprogesterone < 3nmol/L), androgen secreting tumors or suspected Cushing's syndrome. 3. Having known renal disease (creatinine clearance < 60 mL/min), hepatic insufficiency, autoimmune disorders or cancer. 4. Any acute condition with potential to alter renal function or cause tissue hypoxia. 5. Type I diabetes. 6. Pharmacological treatment (cortizon, antidepressant, other antidiabetic treatment such as insulin and acarbose, hormonal contraceptives, hormonal ovulation induction or other drugs judged by discretion of investigator) within 12 weeks. Depo Provera or similar within 6 months. 7. Hypersensitivity to metformin hydrochloride or to any of the excipients. 8. Blood pressure >160 / 100 mmHg 9. Pregnancy or breastfeeding the last 6 months 10. Acupuncture the last 2 months 11. Daily smoking and alcoholic intake 12. Language barrier or disabled person with reduced ability to understand the information given. In total 50 controls will be matched at baseline (age, weight and BMI) to women with PCOS. Controls will undergo screening and baseline visit, but will not be randomized to any treatment