Low-dose combination of flutamide,metformin and an oral contraceptive for non-obese,young women with polycystic ovary syndrome

BACKGROUND: The endocrine-metabolic status of non-obese, young women with polycystic ovary syndrome (PCOS) is normalized more effectively by combined treatment with flutamide and metformin than by either of these drugs in monotherapy. In this follow-up study, we assess whether the endocrine-metabolic benefits of combined flutamide-metformin treatment are maintained in the presence of a low-dose oral contraceptive (OC). METHODS: To a population of non-obese, young PCOS women already receiving flutamide-metformin (125 mg/day and 1275 mg/day), a low-dose OC (ethinyl estradiol 20 microg + gestodene 75 microg) was administered to reduce the risk of pregnancy. A total of 12 women elected to receive the OC and this subgroup (OC+) was matched to a subgroup continuing on flutamide-metformin alone (OC-), for a total study population of 24 women (mean age +/- SEM 18.7 +/- 0.3 years; body mass index, 21.8 +/- 0.5 kg/m(2)). Endocrine-metabolic indices were assessed before any treatment (0 months), on flutamide-metformin (12 months), and again after a further 6 months with or without additional OC (18 months). RESULTS: In OC- and OC+ women, the beneficial effects of flutamide-metformin on hyperandrogenaemia, hyperinsulinaemia and dyslipidaemia were maintained. In OC+ women, there was an additional increase in sex hormone-binding globulin (SHBG), and thus a further drop in the free androgen index. CONCLUSION: When a low-dose OC is administered with a low-dose flutamide-metformin combination in women with PCOS, the beneficial effects are maintained on hyperinsulinaemia-dyslipidaemia, which are key determinants of long-term complications. Hence, in daily practice, such a low-dose quatuor may become a therapeutic option of first choice for young women with PCOS.     

High neutrophil count in girls and women with hyperinsulinaemic hyperandrogenism: normalization with metformin and flutamide overcomes the aggravation by oral contraception

BACKGROUND: The endocrine hallmark of polycystic ovary syndrome (PCOS) is hyperinsulinaemic hyperandrogenism; another facet of PCOS is low-grade inflammation. METHODS: In adolescents and young women with hyperinsulinaemic hyperandrogenism (n = 118; mean age 16 years, body mass index 22 kg/m(2)), we analysed whether the PCOS-associated rise in leukocyte count is already detectable at young age and, if so, whether such elevation is lowered by metformin, flutamide-metformin, oral contraception (OC), or their combination. RESULTS: Leukocyte count (x 1000/mm(3)) in patients was high versus controls (7.5 +/- 0.1 versus 6.4 +/- 0.1; P < 0.001) due to a rise in neutrophils (4.2 +/- 0.1 versus 3.0 +/- 0.1; P < 0.001). Randomized studies at mean ages of 12.5 years (n = 24) and 15.2 years (n = 33) demonstrated normalizing effects of metformin (850 mg/day; P < 0.001) and, respectively, metformin plus flutamide (62.5 mg/day) on neutrophil counts; in young women (18.3 years; n = 41), the neutrophil count rose further on OC monotherapy (P = 0.003), but normalized on the same OC plus flutamide-metformin (P < 0.001 versus OC alone). CONCLUSIONS: (i) A high leukocyte count is already present in girls with hyperinsulinaemic hyperandrogenism, and this is due to a raised neutrophil count; (ii) this hyperneutrophilia is attenuated by metformin or flutamide-metformin, and is amplified by OC monotherapy; (iii) if these treatments are combined, the normalizing effect of flutamide-metformin overcomes the OC effect on neutrophil count.     

Clinical,endocrine and metabolic effects of metformin added to ethinyl estradiol-cyproterone acetate in non-obese women with polycystic ovarian syndrome: a randomized controlled study

BACKGROUND: Oral contraceptive pills (OC) are usually the first choice of treatment for polycystic ovarian syndrome (PCOS), when fertility is not desired. However, they do not improve, or may even further induce impairment of insulin sensitivity, which is already impaired in women with PCOS. In this prospective, randomized study, we analysed the additional benefits of adding metformin to the OC treatment in non-obese women with PCOS. METHODS: After a baseline work-up including body mass index (BMI), waist:hip ratio (WHR), Ferriman-Gallwey score, ovarian volume, serum gonadotrophin, androgen and sex hormone-binding globulin (SHBG) levels, and fasting lipid, glucose and insulin levels, 40 non-obese women with PCOS were assigned either to the OC or to the OC + metformin treatment by computer-assisted randomization. At the end of the 4 month follow-up period, subjects were re-evaluated. RESULTS: The two groups were similar at baseline. After treatment, women in the OC + metformin group had significant decreases in BMI and WHR, and a significant increase in insulin sensitivity, in contrast to those in the OC group, who had insignificant changes in these parameters. Adding metformin also caused significant improvements in serum androstenedione and SHBG levels compared with the OC treatment alone. CONCLUSIONS: Adding metformin to the OC treatment may improve the insulin sensitivity, and may further suppress the hyperandrogenaemia in non-obese women with PCOS.     

Discontinuous low-dose flutamide-metformin plus an oral or a transdermal contraceptive in patients with hyperinsulinaemic hyperandrogenism: normalizing effects on CRP, TNF-alpha and the neutrophil/lymphocyte ratio

BACKGROUND: Low-dose flutamide-metformin (Flu-Met) with an oral contraceptive is a therapeutic option for women with hyperinsulinaemic hyperandrogenism. We questioned (i) whether Flu-Met maintains efficacy if given discontinuously; (ii) how the efficacy of discontinuous Flu-Met plus a transdermal contraceptive compares with Flu-Met plus oral contraceptive; and (iii) whether these treatments also lower circulating C-reactive protein (CRP) and tumour necrosis factor alpha (TNF-alpha) and the high neutrophil/lymphocyte ratio. METHODS: Non-obese, young patients (n = 31) with hyperinsulinaemic hyperandrogenism were started on Flu-Met (21/28 days) and randomized to receive in addition either a drospirenone oral contraceptive or a transdermal contraceptive for 6 months. RESULTS: The effects of Flu-Met were similar whether combined with oral or transdermal contraceptive. In both groups, CRP and TNF-alpha levels fell and the high neutrophil/lymphocyte ratio normalized (P < 0.001). Lean body mass increased (P < 0.001) in both groups but, in contrast to earlier experience with continuous Flu-Met, fat mass failed to decrease in either group. CONCLUSIONS: Flu-Met seems less lipolytic, if given for only 21 days in every 28-day period. The efficacy of Flu-Met is comparable when combined with an oral contraceptive or a transdermal contraceptive. The range of Flu-Met effects may henceforth include lower levels of CRP and TNF-alpha, and a normalization of the neutrophil/lymphocyte ratio.     

Insulin sensitivity in non-obese women with polycystic ovary syndrome during treatment with oral contraceptives containing low-androgenic progestin.

BACKGROUND: Combined oral contraceptives (COC) effectively suppress hyperandrogenism in women with polycystic ovary syndrome (PCOS), though deterioration of insulin sensitivity during treatment is assumed. The study aim was to investigate insulin action and androgen production during treatment with COC containing low-androgenic progestin. METHODS: A total of 13 PCOS women and nine controls was enrolled into the study. Only non-obese women with a body mass index (BMI) 相似文献   

Difference in body weight between American and Italian women with polycystic ovary syndrome: influence of the diet

BACKGROUND: The study aim was to determine differences in body mass in two populations of women (USA and Italy) with polycystic ovary syndrome (PCOS), and to assess the effect of diet on body mass and cardiovascular risk factors. METHODS: Pools of women with PCOS from the USA (n = 343) and Italy (n = 301), seen between 1993 and 2001, were available for assessment. From these populations, 20 women who were seen consecutively in 2001 at each site had detailed analyses of diet and cardiovascular risk factors. RESULTS: In the entire group, American women had a significantly higher body mass compared with Italian women (P < 0.01). Also, the 20 women consecutively evaluated in the USA had a significantly higher mean (+/- SD) body mass index (40.3 +/- 1.0 kg/m(2)) than in Italy (29.7 +/- 1.0 kg/m(2)). US women had worse insulin resistance, lower levels of high-density lipoprotein-cholesterol (HDL-C) (P < 0.01) and higher levels of triglycerides (P < 0.01). Dietary analysis in the two groups indicated that the total daily calorific intake was similar (USA 2277 +/- 109; Italy 2325 +/- 68 Kcal), with no appreciable differences in dietary content of protein, carbohydrate and fat. However, the dietary saturated fat content was significantly higher in US women (31.9 +/- 3 versus 18.2 +/- 2 g/day, P < 0.01). Saturated fat intake correlated negatively with HDL-C (P < 0.01). CONCLUSIONS: Among women with PCOS, body mass was significantly higher in US women compared with Italian women. However, total calorie intake and dietary constituents were similar, except for a higher saturated fat in US women. It is hypothesized that diet alone does not explain differences in body mass; genetic and lifestyle factors likely contribute. An increased saturated fat intake may worsen the cardiovascular risk profile.     

Follistatin and activin A serum concentrations in obese and non-obese patients with polycystic ovary syndrome.

BACKGROUND: Activin promotes ovarian follicular development, inhibits androgen production and increases FSH and insulin secretion. Follistatin, an activin-binding protein, neutralizes activin bioactivity. Therefore, a decrease in the ratio of activin/follistatin might encourage characteristic features of polycystic ovary syndrome (PCOS). We investigated whether women with PCOS showed disordered follistatin and/or activin serum concentrations. METHODS: The study group included 24 obese and 20 non-obese (body mass index vertical line and <27 kg/m2 respectively) clomiphene-failure PCOS patients. The control group included 16 obese and 46 non-obese patients with normal ovulatory cycles. Blood samples were obtained from the patients on day 3-5 of a progesterone-induced or spontaneous cycle and were assayed for LH, FSH, testosterone, 17-hydroxy-progesterone, androstenedione, follistatin, activin A, fasting glucose and insulin. RESULTS: Follistatin concentrations were comparable between obese and non-obese PCOS patients (mean +/- SE; 1171 +/- 103 and 1045 +/- 159 pg/ml respectively) and significantly higher than their respective controls (628 +/- 61 and 592 +/- 49 pg/ml, P < 0.0001 and P < 0.02 respectively). Activin A concentrations were comparable between the four groups (590 +/- 35, 513 +/- 74, 661 +/- 87 and 595 +/- 43 pg/ml in obese and non-obese PCOS and controls respectively). Stepwise regression analyses for relationships between follistatin or activin A levels and all other variables indicated that follistatin was significantly and independently positively affected by PCOS (P < 0.0001), age (P < 0.02), androstenedione (P < 0.03) and weight (P < 0.05). Activin A was significantly and independently negatively affected by PCOS (P < 0.003) and FSH (P < 0.03), and positively affected by weight (P < 0.009) and androstenedione (P < 0.02). CONCLUSIONS: Serum follistatin is increased in PCOS patients, regardless of obesity. PCOS is the most significant variable that relates to high follistatin and low activin A serum concentration. A high follistatin/activin ratio could well contribute to the pathophysiology of PCOS.     

A clinician's response to the oral contraceptive thrombosis controversy

The controversy involving new progestin oral contraceptives (OC) began in late 1995, continued through 1996, and started to reach resolution in 1997. The fundamental question is whether OC containing desogestrel and gestodene have a different risk of thrombosis compared with OC containing older progestins. Correcting for preferential prescribing and the healthy user effect leads to the conclusion that all low-dose OC--regardless of progestin type--have an increased risk of venous thromboembolism. Low-dose OC do not increase the risk of myocardial infarction or stroke in healthy, non-smoking women less than 35 years of age. With effective patient screening for risk factors, the serious side effects of OC can be virtually eliminated.     

Differences in the use of combined oral contraceptives amongst women with and without acne

BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) provides a treatment option for women with acne, hirsutism or polycystic ovary syndrome (PCOS). CPA/EE may be prescribed as an oral contraceptive (OC), but is not licensed as such in the UK. The use of CPA/EE steadily increased after its introduction to the UK market in 1987, but there was a marked increase in its share of the OC market after 1995. METHODS: Using the General Practice Research Database, utilization patterns of CPA/EE and conventional oral contraceptives were compared in women aged 15-39 years, with or without acne or PCOS. RESULTS: Between 1994 and 1998, CPA/EE accounted for an increasing proportion of all OC use. The proportion of CPA/EE prescribed to women with acne declined between 1994 and 1998, whereas that prescribed to women with PCOS remained constant. The age-specific use of CPA/EE by women with acne or PCOS almost doubled. After 1995, there was a marked increase in the use of products containing levonorgestrel by women with acne or PCOS. CONCLUSIONS: A large proportion of CPA/EE is prescribed to women with acne and/or PCOS, although this proportion decreased between 1992 and 1998. This has important implications in CPA/EE risk assessment studies.     

Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome

Body composition, fat distribution and bone mineral density were examined in lean women suffering from polycystic ovary syndrome (PCOS) and compared with body composition and fat distribution characteristics of weight-matched lean controls. Ten women with PCOS and a body mass index (BMI) below 25.00 (kg/m(2)) and 10 healthy women with a BMI below 25.00 (kg/m(2)) matched for age and weight and BMI as controls were enrolled in this study. Body composition and bone density were measured by dual-energy- x-ray-absorptiometry and fat distribution patterns were calculated. Although matched for age, weight and BMI, lean PCOS patients showed a significantly higher amount of body fat and lower amount of lean body mass than the controls. The majority of PCOS patients showed an intermediate or android kind of fat distribution. Only 30% of the lean PCOS patients corresponded to the definition of gynoid fat distribution while this was true of all lean controls.     

Visceral fat is associated with cardiovascular risk in women with polycystic ovary syndrome

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have been reported to have subclinical cardiovascular disease (CVD) and increased abdominal fat. The aim of this study was to evaluate the relationship between visceral fat (VF) and early markers of CVD in PCOS women. METHODS: Two hundred overweight PCOS women [(mean +/- SD) age 24.6 +/- 3.2 years, body mass index (BMI) 28.5 +/- 2.8 kg/m2] and 100 healthy age- and BMI-matched volunteer controls entered this cross-sectional study. In all subjects, the amount of VF was measured by ultrasonography. Anthropometric measurements [BMI and waist circumference (WC)], complete hormonal and metabolic pattern, carotid intima-media thickness (IMT), brachial arterial flow-mediated dilation (FMD) and inflammatory biomarkers [C-reactive protein (CRP), fibrinogen, white blood cells count and plasminogen activated inhibitor-1] were also obtained from all subjects. A stepwise linear regression model was used in PCOS patients to verify if IMT or FMD as dependent variables are affected by other independent variables. RESULTS: VF amount was significantly (P < 0.001) higher in PCOS subjects than in healthy controls [31.4 +/- 7.3 versus 28.0 +/- 6.1 (mean+/-SD) mm, respectively] and directly related to insulin resistance: HOMA (r = 0.918, P < 0.001) and AUC(INS) (r = 0.879, P < 0.001), and to WC (r = 0.658; P < 0.001). In PCOS, the two linear regression analyses showed that IMT is positively affected by VF and CRP, whereas FMD is positively affected by IMT and negatively by VF and CRP. CONCLUSIONS: VF amount is associated with subclinical CVD in PCOS patients.     

Effect of laparoscopic ovarian diathermy on circulating inhibin B in women with anovulatory polycystic ovary syndrome

BACKGROUND: Laparoscopic ovarian diathermy (LOD) frequently induces ovulation in patients with polycystic ovary syndrome (PCOS). The mechanism by which this effect occurs remains largely unexplained. The aim of this study was to measure changes in inhibin B production in response to LOD to see whether this could explain the mechanism of action of LOD. METHODS: This prospective study included 50 anovulatory women with PCOS. All women underwent LOD. Blood samples were collected before and after LOD to measure plasma concentrations of inhibin B, gonadotrophins and androgens. RESULTS: The pre-operative median plasma concentration of inhibin B was 110.0 pg/ml (range 19.0-567.0 pg/ml). There was a statistically significant inverse correlation (r= -0.286; P < 0.05) between body mass index (BMI) and inhibin B. Non-obese women with PCOS (BMI 30 kg/m2; n=13). Following LOD, 39 women ovulated. No statistically significant change of inhibin B after LOD was observed in the overall group of women with PCOS or in the subgroup of non-obese PCOS women with higher pre-operative inhibin B. CONCLUSIONS: The lack of any change of inhibin B after LOD makes it unlikely that this hormone has any role to play in the mechanism of action of LOD.     

Insulin sensitivity, insulin secretion, and metabolic and hormonal parameters in healthy women and women with polycystic ovarian syndrome

To study the contributions of body mass, body fat distribution and family history of type 2 diabetes mellitus to hyperinsulinaemia, insulin secretion and resistance in polycystic ovarian syndrome (PCOS), 17 lean (LC) and 17 obese (OC) healthy control subjects, and 15 lean (LPCOS) and 28 obese (OPCOS) women with PCOS were investigated. Waist:hip ratio (WHR), serum concentrations of sex steroids, glucose and insulin during a 75 g oral glucose tolerance test (OGTT), and insulin and C-peptide early phase secretion, and insulin sensitivity index using a euglycaemic hyperinsulinaemic clamp were assessed. The PCOS subjects had a higher mean WHR than the controls. A trend towards hyperinsulinaemia and impairment of insulin sensitivity (including the rates of both glucose oxidation and non-oxidation) was observed in LPCOS subjects, but only in OPCOS subjects were these changes significant. Early phase insulin secretion but not the early phase C-peptide secretion was increased in PCOS subjects compared to controls, suggesting that peripheral hyperinsulinaemia in PCOS women was mainly due to the observed lowered hepatic insulin extraction and insulin resistance in skeletal muscle. Moreover, the presence of a family history of type 2 diabetes did not affect early phase insulin or C-peptide secretion in the PCOS group. These results confirm and strengthen earlier contentions, that insulin resistance is a characteristic defect in PCOS and is worsened particularly by abdominal obesity.     

Is there a role for leptin in the endocrine and metabolic aberrations of polycystic ovary syndrome?

Immunoreactive serum leptin was analysed in 49 women with polycystic ovary syndrome (PCOS) distributed on a wide range of body mass index (BMI; kg/m2) and in 32 normally menstruating women with comparable age, BMI, physical activity and dietary habits. All women with PCOS had increased androgen concentrations and obese women with PCOS (BMI > or = 25, n=24) also showed decreased insulin sensitivity and a preferential accumulation of truncal-abdominal body fat. Anthropometric and hormonal variables, insulin sensitivity, and pancreatic beta-cell activity were investigated in all women. Percentage body fat was calculated using gender-specific regression equations based on skinfold measurements. Serum leptin concentrations were higher in obese than in non-obese women (P < 0.001), but did not differ between the women with PCOS and controls, nor did they differ between glucose intolerant and glucose tolerant, or hirsute and non-hirsute women with PCOS. Both groups showed strong correlations between serum leptin concentrations and percentage body fat, BMI, body fat distribution, fasting plasma insulin and C-peptide, early insulin secretion, the free androgen index (FAI), and the degree of insulin resistance. After correcting for percentage body fat, only the FAI in the women with PCOS remained significant (P < 0.05). However, in a multiple regression analysis with both percentage body fat and the FAI as independent variables, the FAI increased only minimally (2%) the explained variation in leptin concentrations. Thus, serum leptin concentrations are almost exclusively determined by the total amount of body fat, independent of its location, and do not confirm the hypothesis that leptin is involved in the development of the hormonal and metabolic abnormalities in the PCOS.      

Growth hormone secretion is impaired but not related to insulin sensitivity in non-obese patients with polycystic ovary syndrome

BACKGROUND: The aim of the study was to elucidate the relationship between growth hormone (GH) secretion and insulin resistance in polycystic ovary syndrome (PCOS) patients. In order to exclude the influence of obesity on these parameters, only non-obese PCOS patients were studied. METHODS: Eleven PCOS patients and 11 controls with a body mass index (BMI) 相似文献   

Effect of an oral contraceptive on emotional distress, anxiety and depression of women with polycystic ovary syndrome: a prospective study

STUDY QUESTION: We aimed to determine the impact of an oral contraceptive (OC) treatment on health-related quality of life (HRQOL), depressive and anxiety symptoms in polycystic ovary syndrome (PCOS). SUMMARY ANSWER: OC therapy in PCOS improves hirsutism and menstrual disturbances, along with HRQOL. This improvement is not associated with any change in the prevalence of depressive and anxiety symptoms. WHAT IS KNOWN AND WHAT THIS ARTICLE ADDS: Limited data are available regarding the effects of an OC on HRQOL, and depressive and anxiety symptoms in PCOS. This study reports the effects of the ethinyl estradiol/drospirenone (EE/DRSP) OC on an HRQOL questionnaire for women with PCOS (PCOSQ), depressive and anxiety symptoms after 6 months of treatment. DESIGN: Prospective observational study. All participants completed PCOSQ, Beck Depression Inventory, Hospital Anxiety and Depression Scale and General Health Questionnaire. Serum androgens, fasting insulin, fasting and postload glucose values during an oral glucose tolerance test were measured. Changes in these variables and the scores of questionnaires were evaluated after 6 months of treatment with EE/DRSP (3 mg/30 μg). PARTICIPANTS AND SETTING: Thirty-six patients with PCOS without a previous psychiatric diagnosis were included in the study. MAIN RESULTS AND THE ROLE OF CHANCE: The main complaints of the patients were hirsutism and irregular menses. Accordingly, menstrual and hirsutism problems were the most serious concerns followed by emotional problems on the PCOSQ. Eight patients (22.2%) had clinical depression scores. After treatment, regular menstrual cycles were attained and hirsutism was significantly improved in all patients. Hirsutism and emotion domains of the PCOSQ improved at 6 months (P< 0.05 for both). Depression was improved in five of eight depressive patients and four new patients showed increased depression scores. Overall, depression, anxiety mean scores and depression rates did not show a significant change. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The study is subject to the strengths and limitations of observational study design. A limitation of our study is the small sample size and lack of data related to possible confounding factors. GENERALIZABILITY TO OTHER POPULATIONS: Generalizable to Caucasian PCOS.     

Lack of difference among progestins on the anti-atherogenic effect of ethinyl estradiol: a rabbit study

BACKGROUND: Progestins in combination with estrogen are believed to have different effects on the cardiovascular system. The aim of this study was to investigate the influence of different oral contraceptive formulations on the development of experimental atherosclerosis and vascular reactivity. METHODS: A total of 160 sexually mature rabbits were ovariectomized and randomly assigned to equally large groups: (i) a cholesterol-rich diet (320 mg/day), either given alone (placebo), or together with (ii) ethinyl estradiol (EE 70 micro g/day, oral), (iii) desogestrel (DSG 525 micro g/day, oral), (iv) gestodene (GSD 262.5 micro g/day, oral), (v) levonorgestrel (LNG 525 micro g/day, oral), (vi) EE + DSG, (vii) EE + LNG, or (viii) EE + GSD. After 31 weeks of treatment, aortic accumulation of cholesterol and vascular vasoreactivity (in vitro) were determined. RESULTS: Progestins alone did not reduce the accumulation of cholesterol. EE alone or in combination with a progestin reduced the accumulation of cholesterol relative to placebo (P < 0.0001). Isolated vessels from EE-treated animals relaxed significantly more to physiological concentrations of acetylcholine than did placebo (P < 0.001), whereas vessels treated with EE plus a progestin showed an intermediate response. CONCLUSION: The progestins investigated can be combined with EE without attenuating the anti-atherogenic effect of EE.     

Low-dose flutamide-metformin therapy for hyperinsulinemic hyperandrogenism in non-obese adolescents and women

Polycystic ovary syndrome (PCOS) is a variable disorder that is characterized in adolescents and young women by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity and low-grade inflammation. At present, there is no approved therapy for PCOS. Recent studies indicate that a low-dose combination of flutamide (Flu; a generic androgen-receptor blocker) and metformin (Met; a generic insulin-sensitizer) normalizes the adolescent PCOS spectrum more than an oral contraceptive (OC); in young women, the PCOS spectrum was found to be more normalized by OC plus Flu-Met than by OC alone. Within the pathophysiological cascade of PCOS, Flu-Met seems to counter upstream anomalies like hyperinsulinemia or hyperandrogenism, thereby preventing or reversing downstream effects. In contrast, an OC essentially masks downstream symptoms like hirsutism, acne or irregular menses, whereas the upstream aberrations remain unaltered or may even be worsened. The available experience with Flu-Met is limited but promising. We emphasize that Flu-Met may (as part of its efficacy) induce ovulation but is contra-indicated post-conception because of potential embryotoxicity; therefore, it seems wise to combine Flu-Met with an oral or a transdermal oestro-progestagen or with a non-endocrine method of contraception. May this update prompt further research into Flu-Met's therapeutic potential in patients with PCOS. Until the abovementioned effects have been broadly confirmed, Flu-Met should not be regarded as a standard therapy for widespread clinical practice.     

Cyclic progestin administration increases energy expenditure and decreases body fat mass in perimenopausal women

OBJECTIVE: The menopause transition is characterized by luteal phase defect anovulatory cycles, and changes in body weight and body composition. Resting metabolic rate (RMR) is increased in the luteal phase of the menstrual cycle. We evaluated whether progestin administration increases RMR and influences body composition of perimenopausal women. DESIGN: Thirty-six perimenopausal women were randomly allocated to receive either calcium (1 g/day) continuously plus the progestin nomegestrol acetate (NOMAc; 5 mg/day for 10 days x month for 12 months) or calcium alone. Body composition, RMR, energy intake, and climacteric and psychological symptoms were evaluated at baseline and after 12 months. In the NOMAc group, body composition and RMR analyses were performed twice during the first month of treatment. One evaluation was performed after almost 8 days of NOMAc adjunct, and an another before or almost 15 days after NOMAc administration. RESULTS: Resting metabolic rate was increased by NOMAc administration of 54.5 +/- 73.8 kcal/24 h (P < 0.01). In women treated with NOMAc, fat mass decreased by 1.2 +/- 0.6 kg (P < 0.001). In comparison with controls, body weight (P < 0.05) and body mass index (P < 0.05) were also reduced after 12 months of therapy with NOMAc. CONCLUSIONS: In perimenopausal women the use of NOMAc increases RMR. During the menopause transition, cyclic NOMAc administration may contribute to reduce negative modification of body composition.     

The effect of contraceptive pills on the measured blood loss in medical termination of pregnancy by mifepristone and misoprostol: a randomized placebo controlled trial.

BACKGROUND: A prospective randomized placebo controlled trial was performed to assess the immediate use of oral contraceptive (OC) on the amount of blood loss in the post-abortion period in women undergoing medical abortion by mifepristone and misoprostol. METHODS: One hundred women were randomized by computer to receive either OC pills or placebo, immediately after medical abortion. RESULTS: There was no difference in the complete abortion rate between the two groups. The complete abortion rate was 98 and 92% in the OC and placebo groups respectively. The side-effects and duration of bleeding were also similar. The median days of vaginal bleeding were 17 (range: 3-41) and 15 (range: 5-48) in the OC and placebo groups respectively. There was a statistically significant decrease in the mean haemoglobin level on day 15 in the OC group (from 12.0 to 11.5 g/dl) whereas the mean haemoglobin level in the placebo group remained stable. The median measured blood loss was 69.9 ml in the OC group and 72.8 ml in the placebo group and there was no statistically significant difference between the two groups. CONCLUSION: We conclude that it is safe to offer women combined OC pills immediately after medical abortion as an option of contraception, as it does not affect the duration or amount of vaginal bleeding or the complete abortion rate.