Current treatment for polycystic ovary syndrome: focus on adolescence.

Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women and it is associated with an increased rate of infertility. Its etiology remains largely unknown, although both genetic and environmental factors play a role. PCOS is characterized by insulin resistance, metabolic disorders and low-grade chronic inflammation. To date, the treatment of PCOS is mainly symptomatic and aimed at reducing clinical signs of hyperandrogenism (hirsutism and acne), at improving menstrual cyclicity and at favoring ovulation. Since PCOS pathophysiology is still largely unknown, the therapeutic interventions currently in place are rarely cause-specific. In such cases, the therapy is mainly directed at improving hormonal and metabolic dysregulations typical of this condition. Diet and exercise represent the main environmental factors influencing PCOS. Thus, therapeutic lifestyle changes represent the first line of intervention, which, in combination with oral contraceptives, represent the customary treatment. Insulin resistance is becoming an increasingly studied target for therapy, most evidence stemming from the time-honored metformin use. Relatively novel strategies also include the use of thiazolidinediones and GLP1-receptor agonists. In recent years, a nutraceutical approach has been added to the therapeutic toolkit targeting insulin resistance. Indeed, emerging data support inositol and alpha-lipoic acid as alternative compounds, alone or in combination with the aforementioned strategies, with favorable effects on ovulation, insulin resistance and inflammation. Nevertheless, additional studies are required in adolescents, in order to assess the effectiveness of diet supplements in preventing negative impacts of PCOS on fertility in adult age. This review focuses on the main therapeutic options for PCOS to date.

l-glutamine supplementation exerts cardio-renal protection in estrogen-progestin oral contraceptive-treated female rats.

Glycogen and lipid disruptions represent a spectrum of metabolic disorders that are crucial risk factors for cardiovascular disease in estrogen-progestin oral contraceptive (COC) users. l-glutamine (GLN) has been shown to exert a modulatory effect in metabolic disorders-related syndromes. We therefore hypothesized that GLN supplementation would protect against myocardial and renal glycogen-lipid mishandling in COC-treated animals by modulation of Glucose-6-phosphate dehydrogenase (G6PD) and xanthine oxidase (XO) activities. Adult female Wistar rats were randomly allotted into control, GLN, COC and COC + GLN groups (six rats per group). The groups received vehicle (distilled water, p.o.), GLN (1 g/kg), COC containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and COC plus GLN respectively, daily for 8 weeks. Data showed that treatment with COC led to metabolically-induced obesity with correspondent increased visceral and epicardial fat mass. It also led to increased plasma, myocardial and renal triglyceride, free fatty acid, malondialdehyde (MDA), XO activity, uric acid content and decreased glutathione content and G6PD activity. In addition, COC increased myocardial but not renal glycogen content, and increased myocardial and renal glycogen synthase activity, increased plasma and renal lactate production and plasma aspartate transaminase/alanine aminotransferase (AST/ALT) ratio. However, these alterations were attenuated when supplemented with GLN except plasma AST/ALT ratio. Collectively, the present results indicate that estrogen-progestin oral contraceptive causes metabolically-induced obesity that is accompanied by differential myocardial and renal metabolic disturbances. The findings also suggest that irrespective of varying metabolic phenotypes, GLN exerts protection against cardio-renal dysmetabolism by modulation of XO and G6PD activities.

Major clinical research advances in gynecologic cancer in 2018.

Nineteen topics were selected as major clinical research advances in gynecologic oncology in 2018. For cervical cancer, the importance of human papillomavirus (HPV) testing alone as primary cervical cancer screening method and negative survival impact of minimally invasive surgery in early-stage cervical cancer were addressed. For ovarian cancer, cost-effectiveness of genetic testing to prevent cancer, use of analgesics and oral pill to reduce cancer risk, efficacy of secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, update in the use of poly (ADP-ribose) polymerase inhibitor, and efficacy of anti-angiogenic targeted treatments, including bevacizumab and tyrosine kinase inhibitors, were reviewed. For corpus cancer, sentinel lymph node mapping technique, adjuvant therapy in high-risk endometrial cancer (PORTEC-3), and targeted therapy in recurrent disease were covered. For the field of radiation oncology, survival outcomes of chemoradiation compared with chemotherapy alone in metastatic cervical cancer and new findings regarding the use of neoadjuvant chemotherapy in locally advanced cervical cancer were introduced. Lastly, for breast cancer, the use of talazoparib in patients with germline BRCA1/2 mutation, ovarian suppression for premenopausal patients, adjuvant chemotherapy guided by 21-gene assay, and combination therapy of atezolizumab and nab-paclitaxel for triple-negative cancer as well as promising overall survival results of palbociclib and fulvestrant in advanced breast cancer were briefly mentioned.

Comparative efficacy of oral contraceptive versus local treatment versus intense pulsed light combined with vacuum in endocrine acne in women.

Acne is the most common affection of adolescents, although it can be also found in adult women. Our study was aimed at the comparative assessment of three different therapies over a three-month period, applied to women with moderate comedogenic and papulo-pustular endocrine acne. In the study 116 female patients with endocrine localized face acne were included and divided into three groups: group I with 42 patients was treated with a combination of contraceptive pill + local treatment + pulsed-vacuum light; group II with 38 patients was treated with contraceptives and pulsed-vacuum light and group III with 36 patients was treated only with local treatment. The acne evaluation was made using the Global Acne Grading System (GAGS). Statistical data processing was carried out using the STATA software. For the comedogenic form of acne, the good and very good results were superior in group I vs group II and III (83.33% vs 31.58% vs 5.56%) at the end of the three months of treatment. For the papulo-pustulous form of acne, good and very good results were similar in groups I and II (92.86% vs 73.68%) both after the first month of treatment and at the end of the study, well above the local treatment group (13.99%). Our study highlighted the superiority of laser treatment combined with hormonal treatment, compared to hormonal and local treatment in the comedogenic form of acne, and the superiority of hormonal treatment combined (or not) with laser treatment in the papulo-pustular form compared to local treatment.

Interleukin-6 and Hepcidin Levels during Hormone-Deplete and Hormone-Replete Phases of an Oral Contraceptive Cycle: A Pilot Study.

BACKGROUND: In the past, elevated estradiol levels were reported to downregulate the iron regulatory hormone hepcidin, thereby potentially improving iron metabolism. As estrogen plays a role in regulating the menstrual cycle and can influence the cytokine interleukin-6 (IL-6; a hepcidin up-regulator), this investigation examined the effects of estradiol supplementation achieved by the use of a monophasic oral contraceptive pill (OCP) on IL-6, hepcidin levels and iron status during the hormone-deplete versus hormone-replete phases within an oral contraceptive cycle (OCC). METHODS: Fifteen healthy female OCP users were recruited and provided a venous blood sample on 2 separate mornings during a 28-day period. These included (a) days 2-4 of the OCC, representing a hormone-free withdrawal period (WD); (b) days 12-14 of the OCC, representing the end of the first week of active hormone therapy (AHT). RESULTS: IL-6 and hepcidin levels were not significantly different at WD and AHT. Serum ferritin was significantly higher (p = 0.039) during AHT as compared to WD. CONCLUSIONS: Fluctuations in OCP hormones (estradiol and/or progestogen) had no effect on basal IL-6 and hepcidin levels in young women. Nevertheless, elevated ferritin levels recorded during AHT may indicate that OCP hormones can positively influence iron stores within an OCC despite unchanged hepcidin levels.

Use of Estrogen-Containing Contraception Is Associated With Increased Concentrations of 25-Hydroxy Vitamin D.

CONTEXT: Small studies suggest exogenous estrogen may improve vitamin D status, but the etiology is unclear because women who use hormones may make lifestyle choices that differentially affect vitamin D status. OBJECTIVE: Our objective was to investigate the association between use of hormonal contraception and 25-hydroxy-vitamin D (25(OH)D). DESIGN: We used linear regression modeling of cross-sectional data to estimate percent change in season-adjusted serum 25(OH)D with estrogen use after adjustment for other factors. SETTING: At the enrollment clinic visit (2010-2012) into a cohort study of uterine fibroids, each subject provided a blood sample, had anthropomorphic variables and skin reflectance measured, and answered questionnaires on demographics, dietary and supplement intake, contraceptive use, reproductive and medical history, and behaviors. PARTICIPANTS: A total of 1662 African American women, community volunteers, 23-34 years old, living in the Detroit, Michigan, area were included. INTERVENTIONS: None. MAIN OUTCOMES AND MEASURES: Serum 25(OH)D was measured. RESULTS: Serum 25(OH)D concentrations were low (70% <20 ng/ml). Current use of an estrogen-containing contraceptive was associated with a 20% (95% confidence interval: 14-27) increase in 25(OH)D after adjustment. There was no increase in 25(OH)D among participants who had used estrogen in the past, but were not current users, indicating that results were unlikely to be due to unmeasured confounding by factors related to contraceptive choice. CONCLUSIONS: The increase in 25(OH)D with use of estrogen-containing contraceptives raise mechanistic questions regarding the biological pathways involved, and highlights the need for studies that examine possible endogenous estrogen effects on vitamin D.

Risk Factors for Cataracts Treated Surgically in Postmenopausal Women.

PURPOSE: To identify risk factors for cataracts treated surgically in postmenopausal women. DESIGN: Population-based, prospective cohort study. PARTICIPANTS: A total of 1 312 051 postmenopausal women in the UK Million Women Study, aged 56 years on average (standard deviation [SD], 4.8), without previous cataract surgery, hospital admission with cataracts, or cancer at baseline, were followed for cataracts treated surgically. METHODS: Cox regression was used to calculate adjusted relative risks (RRs) for cataract surgery by lifestyle factors, treatment for diabetes, reproductive history, and use of hormonal therapies. MAIN OUTCOME MEASURES: Cataract surgery identified by linkage to central National Health Service (NHS) records for inpatient and day-patient admissions (Hospital Episode Statistics for England and Scottish Morbidity Records in Scotland). RESULTS: Overall, 89 343 women underwent cataract surgery during an average of 11 (SD, 3) years of follow-up. Women with diabetes were at greatest risk (diabetes vs. no diabetes RR, 2.90; 95% confidence interval [CI], 2.82-2.97). Other factors associated with an increased risk of cataract surgery were current smoking (current smokers of ≥15 cigarettes/day vs. never smokers RR, 1.26; 95% CI, 1.23-1.30) and obesity (body mass index [BMI] ≥30 vs. <25 kg/m(2); RR, 1.12; 95% CI, 1.10-1.14). CONCLUSIONS: Diabetes, smoking, and obesity were risk factors for cataract surgery. Alcohol use, physical activity, reproductive history, and use of hormonal therapies had little, if any, association with cataract surgery risk.

Hormonal versus non-hormonal contraceptives in women with diabetes mellitus type 1 and 2.

BACKGROUND: Adequate contraceptive advice is important in both women with diabetes mellitus type 1 and type 2 to reduce the risk of maternal and infant morbidity and mortality in unplanned pregnancies. A wide variety of contraceptives are available for these women. However, hormonal contraceptives might influence carbohydrate and lipid metabolism and increase micro- and macrovascular complications, so caution in selecting a contraceptive method is required. OBJECTIVES: To investigate whether progestogen-only, combined estrogen and progestogen or non-hormonal contraceptives differ in terms of effectiveness in preventing pregnancy, in their side effects on carbohydrate and lipid metabolism, and in long-term complications such as micro- and macrovascular disease when used in women with diabetes mellitus. SEARCH METHODS: The search was performed in CENTRAL, MEDLINE, EMBASE, POPLINE, CINAHL, WorldCat, ECO, ArticleFirst, the Science Citation Index, the British Library Inside, and reference lists of relevant articles. The last search was performed in January 2013. In addition, experts in the field and pharmaceutical companies marketing contraceptives were contacted to identify published, unpublished or ongoing studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that studied women with diabetes mellitus comparing: 1. hormonal versus non-hormonal contraceptives; 2. progestogen-only versus estrogen and progestogen contraceptives; 3. contraceptives containing < 50 µg estrogen versus contraceptives containing ≥ 50 µg estrogen; and 4. contraceptives containing first-, second- and third-generation progestogens, drospirenone and cyproterone acetate. The principal outcomes were contraceptive effectiveness, diabetes control, lipid metabolism and micro- and macrovascular complications. DATA COLLECTION AND ANALYSIS: Two investigators evaluated the titles and abstracts identified from the literature search. Quality assessment was performed independently with discrepancies resolved by discussion or consulting a third review author. Because the trials differed in studied contraceptives, participant characteristics and methodological quality, we could not combine the data in a meta-analysis. The trials were therefore examined on an individual basis and narrative summaries were provided. MAIN RESULTS: Four randomised controlled trials were included. No unintended pregnancies were reported during the study periods. Only one trial was of good methodological quality. It compared the influence of a levonorgestrel-releasing intrauterine device (IUD) versus a copper IUD on carbohydrate metabolism in women with type 1 diabetes mellitus. No significant difference was found between the two groups. The other three trials were of limited methodological quality. Two compared progestogen-only pills with different estrogen and progestogen combinations, and one also included the levonorgestrel-releasing IUD and copper IUD. The trials reported that blood glucose levels remained stable during treatment with most regimens. Only high-dose combined oral contraceptives and 30 µg ethinylestradiol + 75 µg gestodene were identified as slightly impairing glucose homeostasis. The three studies found conflicting results regarding lipid metabolism. Some combined oral contraceptives appeared to have a minor adverse effect while others appeared to slightly improve lipid metabolism. The copper IUD and progestogen-only oral contraceptives also slightly improved lipid metabolism and no influence was seen while using the levonorgestel-releasing IUD. Only one study reported on micro- and macrovascular complications. It observed no signs or symptoms of thromboembolic incidents or visual disturbances, however study duration was short. Only minor adverse effects were reported in two studies. AUTHORS' CONCLUSIONS: The four included randomised controlled trials in this systematic review provided insufficient evidence to assess whether progestogen-only and combined contraceptives differ from non-hormonal contraceptives in diabetes control, lipid metabolism and complications. Three of the four studies were of limited methodological quality, sponsored by pharmaceutical companies and described surrogate outcomes. Ideally, an adequately reported, high-quality randomised controlled trial analysing both intermediate outcomes (that is glucose and lipid metabolism) and true clinical endpoints (micro- and macrovascular disease) in users of combined, progestogen-only and non-hormonal contraceptives should be conducted. However, due to the low incidence of micro- and macrovascular disease and accordingly the large sample size and long follow-up period needed to observe differences in risk, a randomised controlled trial might not be the ideal design.

Immediate start of hormonal contraceptives for contraception.

BACKGROUND: Health care providers often tell women to wait until the next menses to begin hormonal contraception. The intent is to avoid contraceptive use during an undetected pregnancy. An alternative is to start hormonal contraception immediately with back-up birth control for the first seven days. Immediate initiation was introduced with combined oral contraceptives (COCs), and has expanded to other hormonal contraceptives. At the time of the initial review, how immediate start compared to conventional menses-dependent start was unclear regarding effectiveness, continuation, and acceptability. The immediate-start approach may improve women's access to, and continuation of, hormonal contraception. OBJECTIVES: This review examined randomized controlled trials (RCTs) of immediate-start hormonal contraception for differences in effectiveness, continuation, and acceptability. SEARCH METHODS: In August 2012, we searched MEDLINE, CENTRAL, POPLINE, LILACS, ClinicalTrials.gov, and ICTRP for trials of immediate-start hormonal contraceptives. We contacted researchers to find other studies. Earlier searches also included EMBASE. SELECTION CRITERIA: We included RCTs that compared immediate start to conventional start of hormonal contraception. Also included were trials that compared immediate start of different hormonal contraceptive methods with each other. DATA COLLECTION AND ANALYSIS: Data were abstracted by two authors and entered into RevMan. The Peto odds ratio (OR) with 95% confidence interval (CI) was calculated. MAIN RESULTS: Five studies were included. No new eligible studies have been found since the review was initially conducted. Method discontinuation was similar between groups in all trials. Bleeding patterns and side effects were similar in trials that compared immediate with conventional start. In a study of depot medroxyprogesterone acetate (DMPA), immediate start of DMPA showed fewer pregnancies than a 'bridge' method before DMPA (OR 0.36; 95% CI 0.16 to 0.84). Further, more women in the immediate-DMPA group were very satisfied versus those with a 'bridge' method (OR 1.99; 95% CI 1.05 to 3.77). A trial of two immediate-start methods showed the vaginal ring group had less prolonged bleeding (OR 0.42; 95% CI 0.20 to 0.89) and less frequent bleeding (OR 0.23; 95% CI 0.05 to 1.03) than COC users. The ring group also reported fewer side effects. Also, more immediate ring users were very satisfied than immediate COC users (OR 2.88; 95% CI 1.59 to 5.22). AUTHORS' CONCLUSIONS: We found limited evidence that immediate start of hormonal contraception reduces unintended pregnancies or increases method continuation. However, the pregnancy rate was lower with immediate start of DMPA versus another method. Some differences were associated with contraceptive type rather than initiation method, i.e., immediate ring versus immediate COC. More studies are needed of immediate versus conventional start of the same hormonal contraceptive.

[The use of restorative medicine technologies for the rehabilitation of the patients presenting with endometriosis of external genitalia].

This paper reports the results of analysis of the psycho-emotional status and pain syndrome in the women presenting with endometriosis of external genitalia treated with a combination of hormonal preparations and balneotherapy. A total of 216 infertile patients were involved in the study. The duration of the infertility period varied from 1.5 to 19 years. All the patients underwent surgical intervention. The influence of rehabilitative therapy on the quantitative vital indices (psycho-emotional adaptation to the social environment and pain intensity) was estimated before and after the treatment. The patients were divided into 3 groups. Those of group 1 received an oral contraceptive (30 mcg of ethinylestradiol plus 2 mg dienogest) as a continuous three-cycle course (63 tablets) followed by its discontinuation for the 7 day menstrual period and the final three-cycle course (total duration of therapy 6 months). The patients of group 2 were treated with injections of agonists of gonadotropin releasing hormone (GnRH) at a dose of 3.75 mg once every 4 weeks (total duration 6 months). In group 3, the injections of GnRH agonists (3.75 mg once every 4 weeks, total duration 6 months) were combined with a course of balneotherapy using radon. All the three rehabilitative modalities produced a well-apparent positive effect. Chronic pelvic pain before treatment was reported by 90,3% of the patients. After the treatment, the number of such women in groups 1, 2, and 3 decreased to 20,8%, 12,5%, and 30,6% respectively Dyspareunia in the pre-treatment period was diagnosed in 66,7% of the patients. After treatment, this pathology persisted only in 23,6%, 18,1%, and 31,9% of the patients in groups 1, 2, and 3 respectively. Psycho-emotional disorders before treatment were documented in 90,3% of the patients compared with 27,8%, 25%, and 30,6% after therapy. It is concluded that all the three therapeutic modalities markedly improved health conditions of the patients presenting with endometriosis of external genitalia, but the combination of GnRH agonists with radon therapy produced the most pronounced clinical effect.

Mechanistic and "natural" body metaphors and their effects on attitudes to hormonal contraception.

A small, self-selected convenience sample of male and female contraceptive users in the United Kingdom (n = 34) were interviewed between 2006 and 2008 concerning their feelings about the body and their contraceptive attitudes and experiences. The interviewees were a sub-sample of respondents (n = 188) who completed a paper-based questionnaire on similar topics, who were recruited through a poster placed in a family planning clinic, web-based advertisements on workplace and university websites, and through direct approaches to social groups. The bodily metaphors used when discussing contraception were analyzed using an interpretative phenomenological analytical approach facilitated by Atlas.ti software. The dominant bodily metaphor was mechanistic (i.e.,"body as machine"). A subordinate but influential bodily metaphor was the "natural" body, which had connotations of connection to nature and a quasi-sacred bodily order. Interviewees drew upon this "natural" metaphorical image in the context of discussing their anxieties about hormonal contraception. Drawing upon a "natural," non-mechanistic body image in the context of contraceptive decision-making contributed to reluctance to use a hormonal form of contraception. This research suggests that clinicians could improve communication and advice about contraception by recognizing that some users may draw upon non-mechanistic body imagery.

Comprehensive evaluation of Safyral(®) 2012.

The incidence of pregnancies affected with neural tube defects (NTDs) has been reduced by food fortification programs and public health campaigns promoting folic acid supplementation, but the incidence of NTDs in the USA has not achieved the full potential reduction expected with adequate periconceptional folate utilization. In seeking new ways to access sexually active women at risk for pregnancy, one option would be to link folic acid supplementation to contraceptive use. Since birth control pills are the most popular method of reversible contraception in the USA, it would seem quite logical to find a way to supplement them. To this end, a very efficient folate, levomefolate calcium salt (metafolin), has been added to drospirenone-containing oral contraceptives in equimolar concentrations to the recommended supplements of folic acid to reduce the risk for pregnancy and to reduce the risk of NTDs in pregnancies that occur while women are taking the pill or shortly after they discontinue its use. This article will focus on the need for such folate supplementation and will summarize the contraceptive and noncontraceptive benefits of the 30 µg EE/3 mg drospirenone pill (Yasmin(®), Bayer Healthcare, NJ, USA) to which has been added 451 metafolin (Safyral(®), Bayer Healthcare). The new information about thromboembolism risks associated with use of drospirenone-containing pills is also discussed.

Facilitated acquisition of the classically conditioned eyeblink response in females is augmented in those taking oral contraceptives.

Sex differences in attentional processing and new motor learning remain controversial, and are complicated by the influence of endogenous and exogenous gonadal hormones. Facilitated acquisition of a classically conditioned eyeblink response in oral contraceptive-using women has been reported, as have menstrual cycle-dependent changes in pre-pulse inhibition (PPI). The current study sought to replicate and extend these findings by comparing acquisition of the conditioned eyeblink response and PPI in women currently taking oral contraceptives (OCs), women not taking OCs, as well as men. Women were assigned to participate either during their follicular or luteal menstrual cycle phase. Acquisition was assessed in a two-tone discrimination delay paradigm (500-ms conditional stimulus (CS); 100-ms airpuff unconditional stimulus (US)). PPI was lower in males and OC-users depending on stimulus intensity. Consistent with early classical conditioning research, females acquired an eyeblink conditioned response faster than males. Faster acquisition was associated with larger unconditional responses. Women taking OCs demonstrated accelerated conditioned response acquisition compared to women not taking OCs and males although unconditional responses were comparable to males. Facilitated acquisition of new motor learning in OC-users was replicated in a college-aged population of women and was not secondary to enhanced reactivity to sensory stimuli.

[The influence of sequential hormonal therapy on biochemical and cardiovascular indices in menopause]. / Utjecaj sekvencijske hormonske terapije na biohemijske i kardiovaskularne pokazatelje u menopauzi.

This study follows 94 patients, age 45 to 60, by controlled, random and prospective studies in time period of six months. Out of total number of patients, 53 were divided into research group and treated with hormonal therapy (2 mg of estradiol and 0,5 mg of norgestrel), 41 patients were divided into control group and treated with refemin (Cimicifuga recemosa). Results were statistically processed using Student test and ANOVA, giving us following results: use of HNL resulted with statistically significant changes--increase of heart frequency (*p<0,01), QTc-intervals (**p=0,01), increase of systolic pressure (**p=0,01), increase of diastolic pressure (**p=0,01), increase of body mass index (**p=0,01), endometrial thickness decrease (**p=0,01); use of Cimicifuge recemose resulted with statistically significant changes--increase of diastolic pressure(*p=0,01), increase of body mass index (BMI) (*p=0,01) and endometrial thickness decrease (*p=0,05). By testing research and controlled group with ANOVA test, we have determined that there is statistical difference in operating between recovered hormone therapy and Cimicifuge recemose within parameters of hearth frequency and diastolic pressure.

Hormonal versus non-hormonal contraceptives in women with diabetes mellitus type 1 and 2.

BACKGROUND: Adequate contraceptive advice is important in women with diabetes mellitus type 1 and 2 to reduce the risk of maternal and infant morbidity and mortality in unplanned pregnancies. A wide variety of contraceptives are available for these women. However hormonal contraceptives might influence carbohydrate and lipid metabolism and increase micro- and macrovascular complications. So caution in selecting a contraceptive method is required. OBJECTIVES: To investigate whether progestogen-only, combined estrogen/progestogen or non-hormonal contraceptives differ in terms of effectiveness in preventing pregnancy, in their side effects on carbohydrate and lipid metabolism and in long-term complications such as micro- and macrovascular disease, when used in women with diabetes mellitus. SEARCH STRATEGY: The search was performed in MEDLINE, EMBASE, CENTRAL/CCTR, POPLINE, CINAHL, WorldCat, ECO, ArticleFirst, the Science Citation Index, the British Library Inside, and reference lists of relevant articles. Last search was performed in May 2005. In addition, experts in the field and pharmaceutical companies marketing contraceptives were contacted to identify published, unpublished or ongoing studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that studied women with diabetes mellitus comparing: 1. hormonal versus non-hormonal contraceptives. 2. progestogen-only versus estrogen/progestogen contraceptives. 3. contraceptives containing <50 microg estrogen versus contraceptives containing > or = 50 microg estrogen. 4. contraceptives containing 'first'-, 'second'- and 'third'-generation progestogens, drospirenone and cyproterone acetate. Principal outcomes were contraceptive effectiveness, diabetes control, lipid metabolism and micro- and macrovascular complications. DATA COLLECTION AND ANALYSIS: Two investigators evaluated the titles and abstracts from the literature search. Quality assessment was performed independently with discrepancies resolved by discussion or consulting a third reviewer. Because the trials differed in studied contraceptives, participant characteristics and methodological quality, we could not combine the data in a meta-analysis. The trials were therefore examined on an individual basis and narrative summaries were provided. MAIN RESULTS: Three randomised controlled trials were included. Only one was of good methodological quality. It compared the influence of levonorgestrel-releasing IUD versus copper-IUD on carbohydrate metabolism in women with type 1 diabetes mellitus. No difference was found in daily insulin requirement, glycosylated hemoglobin (HbA1c) or fasting blood sugar after twelve months. The other two trials were of limited methodological quality. Both compared progestogen-only pills with different estrogen/progestogen combinations. The trials reported blood glucose levels to remain stable during treatment with most regimens. Only high-dose combined oral contraceptives were found to slightly impair glucose homeostasis. Combined oral contraceptives also appeared to have a minor adverse effect on lipid metabolism whereas progestogen-only contraceptives slightly improved lipid-metabolism. Only one study reported on micro- and macrovascular complications. No signs or symptoms of thromboembolic incidents or visual disturbances were observed. However study duration was short. Minor adverse effects were reported in one study. The trial found progestogen-only pills to cause more bleeding irregularities when compared with combined oral contraceptives. Unintended pregnancies were not observed during any of the studies. AUTHORS' CONCLUSIONS: The three included randomised controlled trials in this systematic review provided insufficient evidence to assess whether progestogen-only and combined contraceptives differ from non-hormonal contraceptives in diabetes control, lipid metabolism and complications. Two of the three studies were of limited methodological quality, sponsored by pharmaceutical companies and described surrogate outcomes. Ideally, an adequately reported, high-quality randomised controlled trial analysing both intermediate outcomes (i.e. glucose and lipid metabolism) and true clinical endpoints (micro- and macrovascular disease) in users of combined, progestogen-only and non-hormonal contraceptives should be conducted. However, due to the low incidence of micro- and macrovascular disease and accordingly the large sample size and follow-up period needed to observe differences in risk, a randomised controlled trial might not be the ideal design.

[Natural remedies and hormone preparations--potential risk for breast cancer patients. A study surveys the use of agents which possibly counteract with the treatment]. / Naturläkemedel och hormonpreparat- potentiell risk for bröstcancerpatienter. Studie kartlägger bruk av medel som kanske motverkar behandlingen.

We have studied the use of complimentary alternative medicine (CAM) among 233 consecutive breast cancer patients operated on at the Lund University Hospital, Sweden between 2002 and 2004. Questionnaires were administered preoperatively (n = 233), and again 3-6 months post-operatively (n = 167) and one year after surgery (n = 88). At baseline, 14,5% used CAM, 3-6 months post-operatively 14,4% used CAM and one year after surgery 18,2% used CAM. The most common products contained omega-3, garlic, ginseng and roseroot. We identified use of 35 different types of CAM products and seven of these could potentially increase the risk of breast cancer or interact with tamoxifen or aromatase inhibitors: soy, garlic, ginko biloba, echinacea, ginseng, valerian and phytoestrogens (excluding soy). Five and a half percent of the patients used either hormone replacement therapy (HRT) or hormonal contraception at the pre-operative visit, after they had received their breast cancer diagnosis. In conclusion, it is important that doctors discuss the use of CAM and exogenous hormone therapy with their breast cancer patients given the prevalence of these drugs.

Are multiple sclerosis patients risk-takers?

Several factors appear to be associated with multiple sclerosis (MS), and each has a postulated immune or environmental explanation, but a common theme is lacking. This article suggests that a unifying premise could be risk-associated behaviour. Evidence is reviewed for associations with smoking, alcohol, recreational drug use, oral contraception, cholesterol intake, risk attitude and behaviour, ultraviolet light and vitamin D exposure, frequency of MS in healthy societies, and viral infection. The evidence associated with smoking, not taking vitamin D supplements and Epstein-Barr viral infection appears good. There may be a pattern of risk-associated behaviour that characterizes patients with MS and brings them into contact with one or more causative agents. Of the possible agents, viral infection seems the most likely.

Beyond the pill: new data and options in hormonal and intrauterine contraception.

With the goal of helping clinicians facilitate contraceptive success for their patients, this Clinical Opinion provides an update regarding older hormonal and intrauterine contraceptives and details newer methods that include the progestin-releasing intrauterine system, the contraceptive patch and ring, and extended and emergency oral contraception. Last, I will look over the horizon and briefly describe potential future methods that include the single rod progestin-releasing implant, folic acid-supplemented oral contraceptives, and hormonal contraception for men.

Caffeine, postmenopausal estrogen, and risk of Parkinson's disease.

BACKGROUND: Men who regularly consume caffeinated drinks have a lower risk of PD than do nondrinkers, but this relation has not been found in women. Because this sex difference could be due to hormonal effects, the authors examined prospectively the risk of PD according to use of postmenopausal hormones and caffeine intake among participants in the Nurses' Health Study. METHODS: The study population comprised 77,713 women free of PD, stroke, or cancer at baseline, who were postmenopausal at baseline or reached menopause before the end of the study. During 18 years of follow-up the authors documented 154 cases of PD. RESULTS: Overall, the risk of PD was similar in women using hormones and women who never used hormones (relative risk 1.02, 95% CI 0.69 to 1.52). Use of hormones, however, was associated with a reduced risk of PD among women with low caffeine consumption (RR 0.39, 95% CI 0.13 to 1.17), and with increased risk among women with high caffeine consumption (RR 2.44, 95% CI 0.75 to 7.86; p for interaction = 0.01). Among hormone users, women consuming six or more cups of coffee per day had a fourfold higher risk of PD (RR 3.92, 95% CI 1.49 to 10.34; p = 0.006) than did women who never drink coffee. CONCLUSION: These results suggest that caffeine reduces the risk of PD among women who do not use postmenopausal hormones, but increases risk among hormone users. Clinical trials of caffeine or estrogens in women should avoid the combined use of these agents.