Treatment of unfavorable bleeding patterns in contraceptive implant users: a randomized clinical trial of curcumin.

BACKGROUND: Some users of the etonogestrel contraceptive implant experience bothersome bleeding, which can reduce contraceptive satisfaction and continuation. Few strategies exist to manage this bleeding. The exact mechanism of progestin-induced bleeding is unknown, but it is likely multifactorial (eg, impaired angiogenesis, "leaky" fragile vasculature, and inflammation). Curcumin, the active ingredient in turmeric, has anti-inflammatory, antiproliferative, and antiangiogenic properties, which may make it a useful agent for implant-associated bothersome bleeding. OBJECTIVE: This study aimed to evaluate whether curcumin decreases frequent or prolonged bleeding or spotting in contraceptive implant users. STUDY DESIGN: The study was a randomized, double-blind, placebo-controlled trial. Here, etonogestrel implant users with frequent or prolonged bleeding or spotting were enrolled and randomized to either 600-mg Theracurmin HP (Immunovites, Las Vegas, NV) or placebo daily for 30 days. The term "frequent" was defined as ≥2 independent bleeding or spotting episodes, and the term "prolonged" was defined as ≥7 consecutive days of bleeding or spotting in a 30-day interval. Implant use was confirmed by clinical examination and negative gonorrhea and chlamydia and pregnancy tests. Enrolled participants initiated study treatment after 3 consecutive days of bleeding or spotting; if no bleeding or spotting occurred within 30 days of enrollment, the participants were withdrawn from the study. Study treatments were encapsulated to maintain a similar appearance. Participants used text messages to record daily bleeding patterns and study drug compliance. Bleeding was defined as a day that required the use of protection with a pad, tampon, or liner, and spotting was defined as a day with minimal blood loss that did not require the use of any protection. Our primary outcome was the total number of days without bleeding or spotting during the 30 days of study drug or placebo exposure. The secondary outcomes included total number of bleeding-free days, bleeding episodes, and satisfaction. A sample size of 22 per group provided 80% power at an alpha level of .05 to demonstrate a 6-day difference between groups. RESULTS: From February 2021 to November 2022, 58 individuals enrolled in the study with 54 participants (93%) completing 30 days of treatment (26 in the curcumin group and 28 in the placebo group). Of note, 1 individual in the curcumin arm did not experience a qualifying bleeding event and, thus, never initiated treatment and, per protocol, was withdrawn from the study. Participant characteristics did not differ between groups, including length of implant use at study enrollment (placebo, 521±305 days; curcumin, 419±264 days). The study groups did not differ concerning any bleeding-related outcome (mean days without bleeding or spotting: curcumin, 16.7±6.9; placebo, 17.5±4.8; P=.62; mean bleeding-free days: curcumin, 23.4±4.9; placebo, 22.4±4.5; P=.44; bleeding episodes: curcumin, 2.0±0.8; placebo, 2.1±0.8; P=.63). In addition, satisfaction with the implant as contraception and acceptability of bleeding over the study period did not differ by study group (P=.54 and P=.30, respectively). CONCLUSION: Daily use of curcumin did not improve bleeding patterns in users of the etonogestrel contraceptive implant experiencing frequent or prolonged bleeding patterns.

Safety and Acceptability of Community-Based Distribution of Injectable Contraceptives: A Pilot Project in Mozambique.

Mozambique has witnessed a climbing total fertility rate in the last 20 years. Nearly one-third of married women have an unmet need for family planning, but the supply of family planning services is not meeting the demand. This study aimed to explore the safety and effectiveness of training 2 cadres of community health workers-traditional birth attendants (TBAs) and agentes polivalentes elementares (APEs) (polyvalent elementary health workers)-to administer the injectable contraceptive depot-medroxyprogesterone acetate (DMPA), and to provide evidence to policy makers on the feasibility of expanding community-based distribution of DMPA in areas where TBAs and APEs are present. A total of 1,432 women enrolled in the study between February 2014 and April 2015. The majority (63% to 66%) of women in the study started using contraception for the first time during the study period, and most women (over 66%) did not report side effects at the 3-month and 6-month follow-up visits. Very few (less than 0.5%) experienced morbidities at the injection site on the arm. Satisfaction with the performance of TBAs and APEs was high and improved over the study period. Overall, the project showed a high continuation rate (81.1%) after 3 injections, with TBA clients having significantly higher continuation rates than APE clients after 3 months and after 6 months. Clients' reported willingness to pay for DMPA (64%) highlights the latent demand for modern contraceptives. Given Mozambique's largely rural population and critical health care workforce shortage, community-based provision of family planning in general and of injectable contraceptives in particular, which has been shown to be safe, effective, and acceptable, is of crucial importance. This study demonstrates that community-based distribution of injectable contraceptives can provide access to family planning to a large group of women that previously had little or no access.

Preclinical assessments of vaginal microbicide candidate safety and efficacy.

Sexually transmitted infections like HIV, HPV, and HSV-2, as well as unplanned pregnancy, take a huge toll on women worldwide. Woman-initiated multipurpose prevention technologies that contain antiviral/antibacterial drugs (microbicides) and a contraceptive to simultaneously target sexually transmitted infections and unplanned pregnancy are being developed to reduce these burdens. This review will consider products that are applied topically to the vagina. Rectally administered topical microbicides in development for receptive anal intercourse are outside the scope of this review. Microbicide and microbicide/contraceptive candidates must be rigorously evaluated in preclinical models of safety and efficacy to ensure that only candidates with favorable risk benefit ratios are advanced into human clinical trials. This review describes the comprehensive set of in vitro, ex vivo, and in vivo models used to evaluate the preclinical safety and antiviral efficacy of microbicide and microbicide/contraceptive candidates.

Efficacy of fennel and combined oral contraceptive on depot medroxyprogesterone acetate-induced amenorrhea: a randomized placebo-controlled trial.

OBJECTIVES: We aimed to determine the efficacy of fennel and low-dose combined oral contraceptive (LD-COC) on inducing menstrual bleeding and method continuation in women using depot medroxyprogesterone acetate (DMPA) who had no menstrual bleeding within the previous 45 to 140 days. STUDY DESIGN: In this double-blind double-dummy trial, 78 married women referred to public health centers in Hamadan, Iran, who complained of menstrual cessation induced by DMPA were randomly assigned into fennel, LD-COC or placebo groups with an allocation ratio of 1:1:1. All participants received two fennel or placebo capsules and one placebo or LD-COC pill daily for 21 days. We evaluated menstrual bleeding using the Higham pictorial chart within 40 days following initiating intervention. Data were analyzed using chi-square or analysis of variance. RESULTS: There was no loss to follow-up. Significantly more women in the fennel (73%) and LD-COC (81%) groups experienced menstrual bleeding compared to the placebo (19%) group [relative risk (RR) 3.1, 95% confidence interval (CI) 1.6 to 6.2; RR 4.2, 95% CI 1.9 to 9.4, respectively]. Mean amount of menstrual bleeding among those who experienced menstruation was significantly higher in the fennel group (21 cc) than both the LD-COC (14 cc) and placebo (12 cc) groups. Also, women using fennel (73%) and LD-COC (65%) were significantly more likely than those using placebo (31%) to have subsequent DMPA injection [RR 2.5 (95% CI 1.3 to 4.9) and RR 2.0 (95% CI 1.1 to 3.7), respectively]. CONCLUSIONS: Fennel and LD-COC can resolve DMPA-induced amenorrhea and increase continuation rate of this contraceptive method.

Non-surgical interventions for the management of chronic pelvic pain.

BACKGROUND: Chronic pelvic pain is a common and debilitating condition; its aetiology is multifactorial, involving social, psychological and biological factors. The management of chronic pelvic pain is challenging, as despite interventions involving surgery, many women remain in pain without a firm gynaecological diagnosis. OBJECTIVES: To assess the effectiveness and safety of non-surgical interventions for women with chronic pelvic pain. SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group Specialised Register. We also searched (from inception to 5 February 2014) AMED, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS. We handsearched sources such as citation lists, trial registers and conference proceedings. SELECTION CRITERIA: Randomised controlled trials (RCTs) on non-surgical management of chronic pelvic pain were eligible for inclusion. We included studies of women with a diagnosis of pelvic congestion syndrome or adhesions but excluded those with pain known to be caused by endometriosis, primary dysmenorrhoea (period pain), active chronic pelvic inflammatory disease or irritable bowel syndrome. We considered studies of any non-surgical intervention, including lifestyle, physical, medical and psychological treatments. DATA COLLECTION AND ANALYSIS: Study selection, quality assessment and data extraction were performed independently by two review authors. Meta-analysis was performed using the Peto odds ratio (Peto OR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). The primary outcome measure was pain relief, and secondary outcome measures were psychological outcomes, quality of life, requirement for analgesia and adverse effects. The quality of the evidence was assessed by using GRADE methods. MAIN RESULTS: Twenty-one RCTs were identified that involved non-surgical management of chronic pelvic pain: 13 trials were included in the review, and eight were excluded. The studies included a total of 750 women-406 women in the intervention groups and 344 in the control groups. Included studies had high attrition rates, and investigators often did not blind adequately or did not clearly describe randomisation procedures. Medical treatment versus placebo Progestogen (medroxyprogesterone acetate (MPA)) was more effective than placebo at the end of treatment in terms of the number of women achieving a greater than 50% reduction in visual analogue scale (VAS) pain score immediately after treatment (Peto OR 3.00, 95% CI 1.70 to 5.31, two studies, n = 204, I(2) = 22%, moderate-quality evidence). Evidence of benefit was maintained up to nine months after treatment (Peto OR 2.09, 95% CI 1.18 to 3.71, two studies, n = 204, I(2) = 0%, moderate-quality evidence). Women treated with progestogen reported more adverse effects (e.g. weight gain, bloatedness) than those given placebo (high-quality evidence). The estimated effect of lofexidine on pain outcomes when compared with placebo was compatible with benefit and harm (Peto OR 0.42, 95% CI 0.11 to 1.61, one study, 39 women, low-quality evidence). Women in the lofexidine group reported more adverse effects (including drowsiness and dry mouth) than women given placebo (moderate-quality evidence). Head-to-head comparisons of medical treatments Head-to-head comparisons showed that women taking goserelin had greater improvement in pelvic pain score (MD 3, 95% CI 2.08 to 3.92, one study, n = 47, moderate-quality evidence) at one year than those taking progestogen. Women taking gabapentin had a lower VAS pain score than those taking amytriptyline (MD -1.50, 95% CI -2.06 to -0.94, n = 40, low-quality evidence). Study authors reported that no statistically significant difference was observed in the rate of adverse effects among women taking gabapentin compared with women given amytriptyline. The study comparing goserelin versus progestogen did not report on adverse effects. Psychological treatment Women who underwent reassurance ultrasound scans and received counselling were more likely to report improved pain than those treated with a standard 'wait and see' policy (Peto OR 6.77, 95% CI 2.83 to 16.19, n = 90, low-quality evidence). Significantly more women who had writing therapy as a disclosure reported improvement in pain than those in the non-disclosure group (Peto OR 4.47, 95% CI 1.41 to 14.13, n = 48, very low-quality evidence). No difference between groups in pain outcomes was noted when other psychological therapies were compared with standard care or placebo (quality of evidence ranged from very low to low). Studies did not report on adverse effects. Complementary therapy Distension of painful pelvic structures was more effective for pain when compared with counselling (MD 35.8, 95% CI 23.08 to 48.52 on a zero to 100 scale, one study, n = 48, moderate-quality evidence). No difference in pain levels was observed when magnetic therapy was compared with use of a control magnet (very low-quality evidence). Studies did not report on adverse effects.The results of studies examining psychological and complementary therapies could not be combined to yield meaningful results. AUTHORS' CONCLUSIONS: Evidence of moderate quality supports progestogen as an option for chronic pelvic pain, with efficacy reported during treatment. In practice, this option may be most acceptable among women unconcerned about progestogenic adverse effects (e.g. weight gain, bloatedness-the most common adverse effects). Although some evidence suggests possible benefit of goserelin when compared with progestogen, gabapentin as compared with amytriptyline, ultrasound versus 'wait and see' and writing therapy versus non-disclosure, the quality of evidence is generally low, and evidence is drawn from single studies.Given the prevalence and healthcare costs associated with chronic pelvic pain in women, RCTs of other medical, lifestyle and psychological interventions are urgently required.

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.

Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users.

BACKGROUND: Combined hormonal contraceptives (CHCs) place women at increased risk of venous thromboembolic events (VTEs) and arterial thrombotic events (ATEs), including acute myocardial infarction and ischemic stroke. There is concern that three recent CHC preparations [drospirenone-containing pills (DRSPs), the norelgestromin-containing transdermal patch (NGMN) and the etonogestrel vaginal ring (ETON)] may place women at even higher risk of thrombosis than other older low-dose CHCs with a known safety profile. STUDY DESIGN: All VTEs and all hospitalized ATEs were identified in women, ages 10-55 years, from two integrated health care programs and two state Medicaid programs during the time period covering their new use of DRSP, NGMN, ETON or one of four low-dose estrogen comparator CHCs. The relative risk of thrombotic and thromboembolic outcomes associated with the newer CHCs in relation to the comparators was assessed with Cox proportional hazards regression models adjusting for age, site and year of entry into the study. RESULTS: The hazards ratio for DRSP in relation to low-dose estrogen comparators among new users was 1.77 (95% confidence interval 1.33-2.35) for VTE and 2.01 (1.06-3.81) for ATE. The increased risk of DRSP was limited to the 10-34-year age group for VTE and the 35-55-year group for ATE. Use of the NGMN patch and ETON vaginal ring was not associated with increased risk of either thromboembolic or thrombotic outcomes. CONCLUSIONS: In new users, DRSP was associated with higher risk of thrombotic events (VTE and ATE) relative to low-dose estrogen comparator CHCs, while the use of the NGMN patch and ETON vaginal ring was not.

Use of contraceptive methods and contraceptive recommendations among health care providers actively involved in contraceptive counseling -- results of an international survey in 10 countries.

BACKGROUND: This study was conducted to determine the personal choices of contraceptive methods among an international sample of contraception health care professionals (HCPs) and to determine if these choices are concordant with their recommendations to women. STUDY DESIGN: In an anonymous online survey, 1001 HCPs actively involved in contraceptive counseling [obstetrician/gynecologists (OB/GYNs), general practitioners (GPs) and midwives (only in Sweden)] from 10 countries (Australia, Brazil, Canada, France, Germany, Korea, Mexico, Spain, Sweden and the United Kingdom) were asked about their personal use of contraceptive methods and their recommendations to women in two different clinical scenarios: for spacing between children (Group A) and after completion of the family (Group B). RESULTS: The largest HCP group was OB/GYNs (67.1%), followed by GPs (31.4%) and midwives (1.5%). A total of 42.7% of respondents were male, and 57.3% were female. The majority of respondents were aged 36-45 years (38.9%) or 46-55 years (42.8%), 79.7% had children, and 53.9% were currently using contraception (by themselves or by their partners). Among 540 contraceptive users, the three most common methods were the levonorgestrel-releasing intrauterine system (LNG-IUS; 29.3%), combined oral contraceptives (COCs; 20.0%) and condoms (17.0%). OB/GYNs were more likely to be using the LNG-IUS than GPs (p=.014). Gender did not seem to influence contraceptive preference. Reasons for these choices were largely influenced by family situation and high contraceptive efficacy (for the LNG-IUS) or side effects caused by other methods (for condoms). The top contraceptive recommendation was COCs for Group A and the LNG-IUS for Group B. HCPs currently using COCs and the LNG-IUS were more likely to recommend these methods than other contraceptive methods for Group A and Group B, respectively. CONCLUSIONS: The most popular contraceptive method in this sample of HCPs was the LNG-IUS. Choice of contraceptive method was driven by family situation, age and profession. It appears that, in this sample, personal contraceptive use influences contraceptive recommendations.

Is poor nutrition masking the effects of depomedroxyprogesterone acetate on bones in adolescent users?

INTRODUCTION: Research in the developed countries has documented bone loss in adolescents who use depomedroxyprogesterone acetate (DMPA) as a contraceptive for less than two years. DMPA use often begins during adolescence in Bangladesh, a South Asian developing country, where more than 50% of women are undernourished. Poor nutrition is also associated with low bone mineral density (BMD) in South Asian women. We investigated the effects of long-term (two or more years) DMPA use on BMD in Bangladeshi women who started its use in their adolescence. METHODS: Lumbar spine and femur neck BMD were acquired using dual energy X-ray absorptiometry for 100 adolescents (50 DMPA users and 50 non-users) in a cross-sectional study in Dhaka, Bangladesh. Multivariate analysis was used to determine the associations between BMD and DMPA use. Stratified analysis of DMPA use investigated the determinants of BMD in both groups. RESULTS: The participants (mean age 18 +/- 2 years) were generally below their ideal body weight. No significant differences in BMD were found between the two groups. Weight (odds ratio [OR] 0.96, 95 percent confidence interval [CI], 0.92-1.00) and height (OR 0.68, 95 percent CI 0.49-0.94) were independent determinants (p-value is less than 0.05) of lumbar and femur neck BMD, respectively. CONCLUSION: Poor nutritional status, indicated by a less-than-ideal body weight, may be masking the effects of DMPA on bone loss among adolescent users. Our findings suggest that nutritional supplementation may be required with DMPA prescription to promote bone health in adolescent users who are approaching peak bone mass.

Management of recurrent vulvo-vaginal candidosis as a chronic illness.

For sporadic acute Candida vaginitis, any oral or local antifungal therapy can be used. For women with recurrent vulvo-vaginal candidosis (RVC), on the other hand, such simple approaches are insufficient, regardless of the product chosen. Instead, RVC should be managed as any other chronic disease and requires long-term, prophylactic, suppressive antifungal treatment. A regimen using individualized, decreasing doses of oral fluconazole (the ReCiDiF regimen) was proven to be highly efficient and offered great comfort to the patients. During this regimen, it is crucial that patients are carefully examined by anamnestic, clinical, microscopic and culture-proven absence of Candida. If a relapse occurs, the medication is adjusted and efforts are taken to find a possible triggering factor for the reactivation of the infection. Care has to be taken not to accumulate 'don't do's', unless the efficiency of a measure has been proven, by trying to eliminate one risk factor at a time for 2 months. Known possible triggers to be kept in mind are (1) antibiotic use, (2) use of specific contraceptives, especially combined contraceptive pills, (3) disturbed glucose metabolism, (4) the use of personal hygienic products, and (5) tight clothing or plastic panty liners. In therapy-resistant cases, non-albicans infection must be ruled out, and alternative therapies should be tried. Boric acid is proven to be efficient in most of these resistant cases, but other non-azoles like amphotericin B, flucytosine, gentian violet, and even caspofungin may have to be tried. As a final remark it has to be said that many patients feel poorly understood and inefficiently managed by many care-givers, increasing their feelings of guilt and sexual inferiority. Therefore, attention has to be given to take the disease seriously, follow strict treatment regimens, and advise precisely and based on individual evidence concerning any possible risk factors for recurrence. In case of therapy-resistant vulvo-vaginitis, reconsider your diagnosis and/or consider referral to specialized therapists.

Aortobifemoral embolism in an 18-year old patient following cisplatin and 5-fluorouracil chemotherapy for nasopharyngeal carcinoma.

After cisplatin / 5-fluorouracil chemotherapy for nasopharyngeal carcinoma, an 18-year female patient developed aortobifemoral embolism. Besides chemotherapy, additional risk factors for arterial thromboembolic events were smoking, contraceptive medication and adjuvant antiemetic treatment with dexamethasone. Thrombophilia screening was negative. Thromboembolic complications during or after cisplatin have been reported in a frequency of 17.6 % in lung cancer patients, and in 8.4 % of patients with germ cell tumors. The incidence of arterial thromboembolic events was 9.3 % and 1.7 %, respectively. The pathogenesis of cisplatin induced thromboembolism is thought to be caused by endothelial damage leading to endothelial cell dysfunction, increased von Willebrand factor plasma levels, and hypomagnesaemia.

Contraceptive use among solid organ transplant patients: a systematic review.

BACKGROUND: Women undergoing solid organ transplantation are advised to avoid pregnancy for up to 24 months following transplant surgery. STUDY DESIGN: We conducted a systematic review of the literature, from database (PubMed) inception through February 2009, to evaluate evidence on the safety and effectiveness of contraceptive use among women having undergone solid organ transplantation. RESULTS: From 643 articles, eight articles from seven studies satisfied review inclusion criteria; six articles pertained to kidney transplant patients, and two reported on liver transplant patients. Two reports of one prospective cohort of 36 kidney transplant recipients taking combined oral contraceptives (COCs) or using the transdermal contraceptive patch reported no significant changes in biochemical measures after 18 months of use for either group, although 13 women modified antihypertensive medication, and two women discontinued the study because of serious medical complications. Four case reports of five kidney recipients using intrauterine devices reported inconsistent findings, including both beneficial health effects and contraceptive failures. One retrospective, noncomparative study of 15 liver transplant recipients using COCs or the transdermal contraceptive patch found no significant changes in any biochemical measures obtained, no discontinuations or severe complications and no pregnancies after a 12-month follow up. One case report of a liver transplant recipient on cyclosporine and prednisone documented the development of cholestasis associated with high-dose (50 mcg ethinyl estradiol) COC use as treatment for heavy uterine bleeding. CONCLUSIONS: Very limited evidence on COC and transdermal contraceptive patch use among kidney and liver transplant recipients indicated no pregnancies and no overall changes in biochemical measures. Excluding case reports, evidence on other contraceptive methods or contraception among other types of solid organ transplants was not identified.

Effectiveness and tolerability of levonorgestrel intrauterine system in adolescents.

Our objective was to survey the outcome of treatment with levonorgestrel intrauterine system (Mirena LNG-IUS) at 6-18 months in a university affiliated tertiary referral hospital in adolescents. We report on a consecutive case series of 48 adolescents who had Mirena over 8 years as a day-case procedure between 2003 and 2008. The mean age was 15.3 years and all were of white British origin. The commonest indications were menorrhagia and dysmenorrhoea resistant to oral treatment. For 28/48 (58%), menstrual symptoms had a significant impact on quality-of-life; 45/48 (93.4%) reported ongoing significant improvement in their menstrual symptoms and 2/48 (4.2%) had the device removed within 4 months of insertion. We conclude that Mirena is a well tolerated and effective alternative for heavy periods +/- dysmenorrhoea in adolescents who do not respond to oral therapy.

Effects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: a prospective, controlled, randomized study.

BACKGROUND: This study was conducted to compare the effects of the combined contraceptive vaginal ring releasing 15 mcg of ethinylestradiol (EE) and 120 mcg of etonorgestrel daily with the effects of the contraceptive patch, a transdermal system that delivers a daily dose of 20 mcg of EE and 150 mcg of norelgestromin on bone turnover and bone mineral density (BMD) in young fertile women. STUDY DESIGN: On the basis of a randomized, computer-generated list, 40 women desiring contraception were assigned to a 12-month treatment with a patch delivering a daily dose of 20 mcg of EE and 150 mcg of norelgestromin (Evra, Janssen-Cilag, Italy) (Group A, n=20) or to a 12-month treatment with a vaginal ring releasing a daily dose of 15 mcg of EE and 120 mcg of etonorgestrel (NuvaRing, Organon, Italy) (Group B, n=20). Twenty patients underwent no treatment and were used as healthy controls (Group C, n=20). At 3, 6, 9 and 12 months, serum and urinary calcium, osteocalcin and urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD) levels were measured. At baseline and after 12 months, lumbar BMD was determined by dual-energy X-ray absorptiometry. RESULTS: In Groups A and B, urinary PYD and D-PYD at 6, 9 and 12 months were significantly reduced in comparison with basal values and Group C values (p<.05). In Groups A and B, serum calcium levels were significantly increased after 6 months. No significant difference was detected between Group A and Group B in urinary levels of PYD and D-PYD, in calcium levels and in osteocalcin levels. At 12 months, no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values. CONCLUSION: Both contraceptive systems exert a similar positive influence on bone turnover in young postadolescent women.

Medroxyprogesterone acetate impairs memory and alters the GABAergic system in aged surgically menopausal rats.

In women, medroxyprogesterone acetate (MPA) is the most commonly used progestin component of hormone therapy (HT). In vitro, MPA negatively impacts markers of neuronal health and exacerbates experimentally-induced neurotoxicity. There is in vitro evidence that these factors are driven by GABAergic and neurotrophic systems. Whether these effects translate to a negative impact on brain function has not been tested in vivo, clinically or preclinically. Here we evaluate the mnemonic and neurobiological effects of MPA in the surgically menopausal rat. Aged ovariectomized (OVX) rats were given subcutaneous vehicle, natural progesterone, low-dose MPA or high-dose MPA. Multiple cognitive domains were analyzed via the water radial-arm maze (WRAM) and Morris maze (MM). Cognitive brain regions were assayed for changes in the GABAergic system by evaluating GAD protein, the synthesizing enzyme for GABA, and neurotrophins. On the WRAM, both progestin types impaired learning. Further, high-dose MPA impaired delayed memory retention on the WRAM, and exacerbated overnight forgetting on the MM. While neurotrophins were not affected by progesterone or MPA treatment, both progestin types altered GAD levels. MPA significantly and progesterone marginally decreased GAD levels in the hippocampus, and both MPA and progesterone significantly increased GAD levels in the entorhinal cortex. These findings suggest that MPA, the most commonly used progestin in HT, is detrimental to learning and two types of memory, and modulates the GABAergic system in cognitive brain regions, in aged surgically menopausal rats. These findings, combined with in vitro evidence that MPA is detrimental to neuronal health, indicates that MPA has negative effects for brain health and function.

The use of depot-medroxyprogesterone acetate in contraception and its potential impact on skeletal health.

BACKGROUND: In the fall of 2007, the controversy about the contraceptive use of depot-medroxyprogesterone acetate (DMPA) and its potential impact on skeletal health reached the media in the province of Quebec, Canada, thereby becoming a matter of concern for the lay public and physicians. In order to discuss this subject openly, the National Institute of Public Health of Quebec (INSPQ) organized a scientific meeting on February 15, 2008, with targeted physicians delegated by their medical associations in the fields of general practice, obstetrics and gynaecology, rheumatology, orthopaedic surgery, physiatry and endocrinology. STUDY DESIGN: Participants reviewed the scientific literature using the study classification method according to the level of evidence, reviewed published guidelines of medical societies and organizations on the subject and reached a consensus position. This manuscript presents a review of the literature and describes the consensus position of the targeted medical associations. RESULTS: The consensus position adopted by all the targeted medical associations determined that DMPA was a cost-effective contraceptive option that must be considered in the light of the clinical situation and preference of each woman. Candidates for injectable contraception should be informed that the use of DMPA is associated with a slight decrease in bone mineral density (BMD), which is largely, if not completely, reversible. There should not be an absolute limit to the length of time that the DMPA contraceptive is used, regardless of the woman's age. Monitoring BMD is not recommended among users of DMPA for contraceptive purposes. Finally, the consensus statement declared that, although supplements of calcium and vitamin D are beneficial for skeletal health for women in general, such supplementation should not be recommended solely based on a woman's use of DMPA. CONCLUSION: Given the scientific evidences, DMPA use remains a valid contraceptive option for women. Its potential impact on BMD must be balanced against the significant individual, familial and social consequences of unintended pregnancy.

Depo-Provera and skeletal health: a survey of Florida obstetrics and gynecologist physicians.

OBJECTIVE: In November of 2004, the US Food and Drug Administration (FDA) issued a black box warning regarding skeletal health concerns with depot medroxyprogesterone acetate (DMPA) contraception. This FDA labeling change has the potential to impact how this contraceptive is used. Our goal was to assess the impact of the FDA decision on how Florida obstetrician-gynecologists prescribe DMPA. METHODS: A survey was conducted with questions and case scenarios regarding the use of DMPA before and after the black box warning. The survey was sent to all members of the Florida Obstetric and Gynecologic Society. RESULTS: Four hundred twenty-five surveys were mailed and 149 were returned - a 35% return rate. Forty-six percent of physicians surveyed indicated that they place a time limit on DMPA use, and 66% stated that this limit was based on the FDA black box warning. Sixty-five percent of respondents ordered bone mineral density (BMD) testing solely due to the use of DMPA, with 58% indicating that this decision was based on the black box warning. Eight (5.4%) of the respondents indicated they selectively prescribe bisphosphonates for patients based solely on the use of DMPA, while 33% of respondents state that they use estrogen supplementation. There was a trend towards fewer DMPA injections per week after the black box warning as compared to before; however, this trend was not statistically significant (p<.125). CONCLUSION: Respondents may be writing fewer prescriptions for DMPA, are likely to institute a time limit on said prescription and are likely to order BMD testing, using the black box warning as justification. Continued education is necessary to prevent inappropriate restrictions on DMPA use and the performance and/or prescription of inappropriate tests and medications.

Incidence, aetiology, and outcomes of cancer in Indigenous peoples in Australia.

An assessment of recent data on cancer in Indigenous Australians (Aborigines and Torres Strait Islanders) shows that, although they are less likely to have some types of cancer than other Australians, Indigenous people are significantly more likely to have cancers that have a poor prognosis, but are largely preventable, such as lung and liver cancer. Indigenous people with cancer are diagnosed at a later stage, are less likely to receive adequate treatment, and are more likely to die from their cancers than other Australians. Inadequate identification of Indigenous people in cancer registers precludes reporting for some parts of Australia, but sufficient information is available to identify priorities and inform appropriate remedial action. Health-risk factors, especially smoking, and inadequate health-system performance largely explain the patterns of cancer incidence and mortality in areas with adequate data. Effective tobacco control programmes, improvements across a range of health services, and meaningful Indigenous engagement are all needed to decrease the burden of cancer in Indigenous Australians.

Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive.

BACKGROUND: This study compared metabolic, hormonal and lipid profiles before and during use of a contraceptive vaginal ring (RING) releasing 15 mcg ethinyl estradiol (EE) and 120 mcg etonogestrel per day NuvaRing, Organon USA Inc., Roseland, NJ versus a low-dose oral contraceptive (PILL) containing 20 mcg EE and 100 mcg levonorgestrel daily (Aviane, Barr Pharmaceuticals Inc., Pomona, NY). STUDY DESIGN: Sixty-five women were randomized to either the RING or PILL treatment for five cycles. In the pretreatment cycle (Cycle Days 2-5) and during Weeks 2 and 3 of the fifth treatment cycle, a 75-g oral glucose tolerance test (OGTT) was performed. Baseline samples were used to evaluate basal hormonal, metabolic and lipid levels. RESULTS: Forty-two women completed the study. Basal insulin resistance (HOMA-IR) was slightly decreased, whereas a significant reduction in the insulin sensitivity index (IS(OGTT)) was found in women on PILL therapy compared to those in the RING group (p<.035). Pancreatic beta-cell function was not significantly altered with either treatment. CONCLUSION: The lower-dose, nonoral hormonal RING had a lesser impact on carbohydrate metabolism and greater reduction of free androgen and dehydroepiandrosterone sulfate levels than PILL treatment.