Metformin versus orlistat in the treatment of overweight and obese women with polycystic ovary syndrome (PCOS): A systematic review and meta-analysis

OBJECTIVES: To compare the effects of metformin and orlistat in terms of reduction in weight or BMI, and improvement of ovulation rates, endocrinologic and lipid profiles, and occurrence of adverse events among overweight or obese women diagnosed with PCOS. SEARCH METHODS: We searched Medline, OVID, HERDIN, EMBASE, Cochrane Library and ClinicalTrials.gov for head to head clinical trials of metformin versus orlistat for the treatment of overweight and obese women with PCOS. We also contacted the pharmaceutical companies and did hand-searching to look for related studies. SELECTION CRITERIA: Only randomized controlled trials comparing metformin and orlistat as treatment for overweight and obese PCOS women were included. Other inclusion criteria included: trial period of at least 3 months duration, participants, of any ethnicity, 18-40 years old, who are overweight or obese, and studies with or without non-pharmacologic interventions as part of the treatment regimen. DATA COLLECTION AND ANALYSIS: Titles and abstracts identified through the search strategies were screened by two reviewers. Two authors extracted data on publication characteristics, inclusion and exclusion criteria, intervention and co-intervention, primary and secondary outcomes, and details of study design. Two authors assessed the quality and risk bias of each RCT based on random sequence generation, allocation concealment, blinding of participants, caregivers, and assessors, attrition bias, incomplete outcome data, selective reporting, and publication bias. MAIN RESULTS: We included 5 RCTs (n=221). Overall, treatment effects of orlistat and metformin showed no significant difference in the following outcomes: ovulation rates (RR 0.78; 95% CI 0.41, 1.49), reduction of BMI (MD -0.47; 95%CI:-1.53,0.59), serum testosterone levels (MD -2.15;95% CI -9.64, 5.33), free androgen index MD 3.26; 95% CI -7.91, 14.43), homeostatic model assessment-insulin resistance (3.70; 95% CI -6.74, 14.15), fasting insulin (MD 7.86; 95% CI -3.09, 18.81), HDL-C (MD -1.19 ; 95% CI -4.78, 7.16) and triglycerides (MD -1.95; 95% CI -8.81, 4.90). Orlistat was significantly better than metformin in reducing total cholesterol (MD -6.60; 95% CI -10.79, -2.41), and LDL (MD -5.04; 95% CI -9.64, 5.33), free androgen index (MD 3.26; 95% CI -7.91, 14.43), homeostaic model assessment-insulin resistance (3.70; 95% CI -6.74, 14.15), fasting insulin (MD 7.86; 95% CI -3.09, 18.81), HDL-C (MD -1.19 ; 95% CI -4.78, 7.16) and triglycerides (MD -1.95; 95% CI -8.81, 4.90). Orlistat was significantly better than metformin in reducing total cholesterol (MD -6.60; 95% CI -10.79, -2.41), and LDL (MD -5.04); 95% CI  -9.99, -0.09), and had less adverse events (RR 0.37, 95% CI 0.14, 0.96). AUTHORS' CONCLUSIONS: Metformin and Orlistat have similar effects on weight loss, ovulation rates, and endocrinologic profiles of obese women with PCOS. Orlistat is more effective than metformin in decreasing total cholesterol and LDL -C levels, and has less adverse events than metformin. Therefore, we may recommend orlistat to overweight or obese women with PCOS who also have dyslipidemia. However, caution is given to our interpretations since small sample size, low quality of RCTs, and wide confidence intervals of pooled estimates significantly influence interpretation and recommendations. RCTs with adequately powered study populations are recommended to confirm findings of this review.

A rare case of virilizing ovarian steroid cell tumor in a 46 year-old woman: A case report and review of literature / Philippine Journal of Obstetrics and Gynecology

Virilization is the masculinization and enhancement of male secondary sexual characteristics in females. The etiology may be of adrenal or ovarian in origin. This case report shows a 46 year old woman who presented with defeminizing and virilizing symptoms. Further laboratory investigations revealed increased serum androgen levels and normal CT scan of the adrenals and kidneys. An ovarian mass was confirmed by transrectal ultrasonography. Following a total abdominal hysterectomy and bilateral salpingooophorectomy, histopathological and immunohistochemistry studies on the left ovarian mass confirmed an androgen-secreting, steroid-cell tumor, not otherwise specified (NOS). Serum testosterone values abruptly declined to normal levels within 1 month post-surgery. This paper likewise discusses an extensive review of literature regarding this rare ovarian tumor.

A second - look hysteroscopy after treatment of genital tuberculosis in an amenorrheic woman

A 32 year old G2P1 (1011) presented with amenorrhea of 2 years duration. Both sister and grandfather were diagnosed with Pulmonary Tuberculosis 10 years ago and adequately treated for 9 months with quadruple anti-Koch`s medications. Patient presented with no sign nor symptoms highly suspicious for tuberculosis. Physical and Pelvic examinations, complete endocrinologic investigations, chest X-ray and transvaginal ultrasound all revealed normal results. Progesterone challenge test failed to elicit withdrawal bleeding. Hyteroscopy showed a globularly fibrotic endometrial cavity, while endometrial biopsy revealed chronic granulomatous inflammation with Langhan`s giant cell typical of genital tuberculosis. She was subsequently started on anti-Koch`s medications for 6 months, with prompt resumption of menses after treatment. Second-look hysteroscopy on readmission showed normal, healthy-looking endometrium with no areas of fibrosis. Repeat endomentrial biopsy revealed benign secretory phase endometrium, with absolutely no evidence of chronic granulomatous inflammation. This paper aimed to underscore the value of hysteroscopy as a vital tool in the work-up amenorrhea, and to demonstrate, using second look hysteroscopy, the efficacy of anti-tuberculosis treatment on the uterine cavity in an amenorrheic woman diagnosed with genital tuberculosis.

Pure sertoli cell tumor of the ovary, a rare cause of isosexual pseudoprecocious puberty in a two year old girl

A case of a two and a half year old girl with a 6 month history of isosexual precocious puberty (thelarche: Tanner stage 2 breasts and menarche) secondary to an estrogenizing pure Sertoli cell tumor of the left ovary is presented. Pre-operative tumor markers AFP, BhCG and CA-125 revealed normal results. Transabdominal ultrasound with color flow mapping and Doppler interrogation revealed a solid left ovarian mass probably malignant. The patient underwent exploratory laparotomy, left salpingooophorectomy and frozen section revealing sex cord stromal tumor. Paraffin sections stained with Hematoxylin and Eosin revealed a benign Sertoli cell tumor. Immunostains of the tumor reacted positively for inhibin, calretenin and cytokeratin, but negative for epithelial membrane antigen. Total serum estradiol, prolactin, TSH and LH were elevated prior to surgical operation, with LH and prolactin substantially decreasing four weeks later into the normal prepubertal range. TSH and estradiol levels however have remained very slightly elevated. Serum FSH was at prepubertal levels. Breasts size had likewise regressed to prepubertal size four weeks postoperatively, and the menses never recurred. This is the youngest reported occurrence of this rare sex cord stromal neoplasm in the last 10 years in our institution. The prognosis of this extremely rare tumor presenting at this early juvenile stage is uncertain, and it is recommended to keep a close follow-up and regular endocrinologic investigation until prepubertal values are attained.