Gökalp Öner

The effects of metformin and letrozole on endometriosis and comparison of the two treatment agents in a rat model

BACKGROUND Our aim was to investigate the effects of metformin and letrozole on experimentally induced endometriosis in a rat model. METHODS Endometriotic implants were surgically formed, and 38 rats were randomly divided into four groups. Group 1 (control group, 8 rats) was given no medication. Group 2 (metformin group, 10 rats) was given 100 mg/kg/day of oral metformin. Group 3 (metformin group, 10 rats) was given 200 mg/kg/day of oral metformin. Group 4 (letrozole group, 10 rats) was given 0.1 mg/kg/day of oral letrozole. All rats continued to receive the treatment for 4 weeks and then were sacrificed to assess the size of implants and scores of adhesions. The histopathologic scores of implants in excised endometriotic foci were examined by a pathologist. RESULTS The mean surface area of endometriotic implants was similar in all groups before the treatment. Although the area was not reduced in controls, it was found to be significantly reduced in all treatment groups (44.50 +/- 23.37, 5.90 +/- 2.37, 4.30 +/- 1.33, 6.90 +/- 3.72 mm(2), respectively; P < 0.05). The effect was comparable between the treatment groups. The histopathologic assessment revealed that the histopathologic score of implants was lowest after 100 mg/kg/day metformin. Additionally, metformin reduced the severity of adhesions. CONCLUSIONS Metformin and letrozole caused a statistically significant regression of endometriotic implants. The effects of metformin on endometriotic tissue were at least comparable to letrozole.

Clinical, endocrine and metabolic effects of metformin vs N-acetyl-cysteine in women with polycystic ovary syndrome

OBJECTIVE To evaluate the clinical, endocrine and metabolic effects of metformin and N-acetyl-cysteine (NAC) in patients with polycystic ovary syndrome (PCOS). STUDY DESIGN In this prospective trial, 100 women with PCOS were randomly divided to receive metformin (500 mg p.o. three times daily) or NAC (600 mg p.o. three times daily) for 24 weeks. Hyperandrogenism, lipid profiles, hirsutism scores, menstrual irregularity, insulin sensitivity and tumour necrosis factor-α (TNF-α) levels were measured at baseline and after the treatment period. RESULTS Both treatments resulted in a significant decrease in body mass index, hirsutism score, fasting insulin, HOMA index, free testosterone and menstrual irregularity compared with baseline values, and both treatments had equal efficacy. NAC led to a significant decrease in both total cholesterol and low-density lipoprotein levels, whereas metformin only led to a decrease in total cholesterol level. Although TNF-α levels increased following treatment for both groups, the difference from baseline was not significant. CONCLUSIONS Metformin and NAC appear to have comparable effects on hyperandrogenism, hyperinsulinaemia and menstrual irregularity in women with PCOS. The effects of metformin and NAC on insulin sensitivity are not associated with TNF-α.

Efficacy of omega-3 in the treatment of polycystic ovary syndrome.

The purpose of this study was to evaluate the efficacy and safety of omega-3 in the treatment of polycystic ovary syndrome and to compare the clinical, hormonal, TNF-α and resistin levels in the patients treated with omega-3. A total of 45 non-obese PCOS women were studied. Women were treated with daily oral 1,500 mg of omega-3 for 6 months. Body mass index (BMI), hirsutism score, fasting glucose and insulin levels were noted for each case. Hirsutism was assessed at 6-month intervals using the Ferriman–Gallwey (F–G) scoring system. Hormonal, TNF-α and resistin levels at 6 months of therapy were compared with baseline values. BMI, F–G scoring, insulin and HOMA levels decreased significantly during treatment, but glucose levels did not change. In the hormonal profile, serum LH and testosterone levels decreased and sex hormone-binding globulin levels increased significantly after the 6 months of therapy. On the other hand, TNF-α levels showed a significant increase, whereas resistin levels showed no change. Omega-3 may be also effective in improving hirsutism and insulin resistance in patients with PCOS.

Comparison of antiproliferative effects of metformine and progesterone on estrogen-induced endometrial hyperplasia in rats

Abstract Metformin has been shown to inhibit the growth of endometriotic implants, and reverse endometrial hyperplasia when combined with oral contraceptive in a case report. The aim of this study is to compare the antiproliferative effects of medroxyprogesterone acetate (MPA), and metformin in oopherectomized rat endometrium. Forty oopherectomized Wistar-Albino rats were used, and assigned to receive saline, 17 β Estradiol hemihydrate (4 mg/kg), 17 β Estradiol hemihydrate (4 mg/kg) and metformin (50 mg/kg), 17 β Estradiol hemihydrate (4 mg/kg) and MPA (1 mg/day) for 14 days. Histological markers of uterotrophy, including endometrial height, luminal ephitelial cell height and density of endometrial glands on hysterectomy speciments were quantified for each specimen. Rats treated with estradiol had significantly increased in endometrial height, endomerial luminal epithelial height and endometrial gland densitiy than the other groups. Metformin and MPA acetate significantly reduced all parameters indicating endometrial hyperplasia, and uterotrophy with respect to the control group. Antiproliferative effects of metformin, and MPA was found to be comparable for all three parameters. In conclusion, metformin attenuates estrogen-induced endometrial hyperplasia in ooferectomized rats to the same degree as progesterone.

The influence of obesity on ICSI outcomes in women with polycystic ovary syndrome

The objective of the study was to compare intracytoplasmic sperm injection (ICSI) outcome and gonadotropin doses between obese women with PCOS and non-obese patients with PCOS. This follow-up study represents ICSI outcomes in obese women with PCOS (BMI ≥ 30 kg/m2) compared with non-obese women with PCOS (BMI < 30 kg/m2). Obese (n = 18) and non-obese (n = 26) women with PCOS underwent long protocol pituitary suppression, ovarian stimulation and ICSI with fresh embryo transfer. Obese patients with PCOS required higher doses of gonadotropin (2994 IU vs 1719 IU; p < 0.001). Miscarriage rate was significantly higher in obese women compared with the non-obese women with PCOS (60% vs 6.7%, p = 0.002). Our results are valuable for counselling couples before initiation of assisted reproduction techniques (ART).

A prospective randomized trial comparing low-dose ethinyl estradiol and drospirenone 24/4 combined oral contraceptive vs. ethinyl estradiol and drospirenone 21/7 combined oral contraceptive in the treatment of hirsutism

BACKGROUND A prospective randomized trial was conducted to compare the clinical efficacy of two oral contraceptives containing drospirenone in the treatment of hirsutism in women. STUDY DESIGN Fifty women with moderate to severe hirsutism were recruited. Three women were lost to follow-up. Twenty-four patients received oral 0.03 mg ethinyl estradiol and 3 mg drospirenone 21/7 regimen (Group 1) for 6 months. Another group of 23 patients received oral 0.02 mg ethinyl estradiol and 3 mg drospirenone 24/4 regimen (Group 2) for 6 months. Hirsutism was assessed after 6 months using the Ferriman-Gallwey (F-G) scoring system. Hormonal levels after 6 months of both therapies were compared with baseline values and each other. RESULTS An improvement in the F-G scores for hirsutism (mean±SD) was observed in Group 1 (17.3±5.2 to 8.7±2.5, p<.001) and in Group 2 (17.5±4.8 to 7.9±2.8, p<.001). Pre- and post-treatment hirsutism scores were comparable between the groups (p>.05). Total and free testosterone levels decreased significantly after the therapy in both groups. The sex hormone-binding globulin levels increased significantly in both groups during the 6-month period. CONCLUSION The treatment of hirsutism with both combined oral contraceptives (COCs) containing drospirenone offered comparable effects and was well tolerated.

Removal of ascites up to 7.5 liters on one occasion and 45 liters in total may be safe in patients with severe ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially lethal complication of ovulation induction. We report herein a case with OHSS treated by serial vaginal paracentesis. A 31-year-old patient was hospitalized due to severe OHSS after in vitro fertilization (IVF)–embryo transfer. Transvaginal drainage was performed with a standard 17-gauge IVF needle connected to a vacuum pump through a drainage set in nine courses. We removed 45 liters of ascitic fluid in total and 7.5 liters of ascitic fluid in one course, leading to improvement of the patients condition and laboratory parameters. In conclusion, removal of ascites up to 7.5 liters on one occasion and 45 liters in total by serial vaginal paracentesis may be performed in patients with severe OHSS.

The effects of metformin and letrozole on endometrium and ovary in a rat model

Objective: The effects of metformin and letrozole on endometrium and ovarian reserve were studied in a rat model. Methods: Forty female Wistar albino mature rats at 8 weeks, weighing 180–260 g, were used for the study. These rats were randomly divided into four groups. Control group, eight rats, was given no medication by oral gavage. The rats in low-dose metformin group, 10 rats, were given 100 mg/kg/day of oral metformin. The rats in high-dose metformin group, 10 rats, were given 200 mg/kg/day of oral metformin. The rats in letrozole, 10 rats, were given 0.1 mg/kg/day of oral letrozole. Results: There was statistically significant difference in the endometrial thickness between the treatment groups and control group. The primordial follicle count was comparable in all treatment groups compared with control. Finally, there was no significant difference in total follicle count between the treatment groups and control. Conclusions: This study showed that both metformin and letrozole had similar effects on endometrium and ovary in the rat model. Additionally, metformin had a little effect on endometrium than letrozole. Although metformin and letrozole might have tendency to enhance the total follicle count in the rat model, they had comparable effects on ovarian follicles and did not change the ovarian reserve compared with control.

Assessment of ovarian reserve based on hormonal parameters, ovarian volume, and antral follicle count in women with familial Mediterranean fever

OBJECTIVE To evaluate ovarian reserve in women with familial Mediterranean fever (FMF). STUDY DESIGN Thirty women with FMF (20-29 years) and thirty healthy controls (20-29 years) were admitted to this study. Basal serum levels of follicle-stimulating hormone (FSH), oestradiol (E2), luteinizing hormone (LH) and inhibin B were measured on cycle day 3. All participants underwent transvaginal ultrasonographic examination on the third day of their menstrual cycle for the determination of ovarian volume (OV) and total antral follicle count (AFC). RESULTS Women with FMF had significantly higher concentrations of FSH, LH and E2 than healthy controls. Total AFC was significantly lower in women with FMF than in healthy controls. OV was also lower in the FMF group but there was no statistically significant difference in OV between the groups. Age was negatively associated with FSH and LH. Inhibin B was found to be negatively correlated with LH and OV. CONCLUSIONS In this preliminary study, the first in FMF patients, we found that ovarian reserve was reduced in women with FMF compared with healthy controls. FMF may affect the ovarian reserve but the mechanism of this effect is unclear.

Sex Hormones and Infertility

The normal physiology of the female reproductive system involves a hypothalamus that secretes gonadotropin-releasing hormone (GnRH)in a pulsatile manner, a pituitary gland that can be stimulated by the hypothalamus to regularly secrete both luteinizing hormone (LH) and follicle-stimulating hormone (FSH), an ovary that has both methodical enzymatic system and steroidogenesis for producing the sex hormones such as estrogen and progesteron, and a functional uterus that can be responded by these hormones. Sex hormones play a crucial role in reproductive biology as well as in general physiology. The most important aim of sex hormones is to design the cycle and to produce an optimal environment for pregnancy according to form ovarian physiology including follicular growth, ovulation, and corpus luteum formation and endometrial response including proliferative and secretuar phase for implantation. Among the various functions, sex hormones influence pregnancy, cardiovascular function, bone metabolism, and an individuals sense of general well-being. The action of sex hormones is mediated via extracellular signals to the nucleus to affect a physiologic response.