Ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women with polycystic ovary syndrome

Objective To evaluate whether the presence of polycystic ovary syndrome (PCOS) alters multiple ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women without any other health condition that could interfere with combined oral contraceptive (COC) eligibility criteria. Methods This was a case- control study evaluating 90 obese women ( body mass index ( BMI) = 30.0 kg/m2 and < 40 kg/m2) aged between 18 and 40 years without any other health condition that could interfere with COC eligibility criteria, of whom 45 had PCOS and 45 were age- matched controls. BMI, waist and hip circumference, arterial blood pressure, fasting insulin and glucose, quantitative insulin sensitivity check index ( QUICKI), highdensity lipoprotein cholesterol, low- density lipoprotein cholesterol, total cholesterol, triglycerides, testosterone, sex hormone- binding globulin, free androgen index ( FAI), carotid stiffness index, intima media thickness, flowmediated dilatation ( FMD) of the brachial artery and non- alcoholic fatty liver disease ( NAFLD) were assessed. Results In women with PCOS, we observed a higher frequency of NAFLD ( 73.3 vs. 46.7%, P < 0.01) and higher FAI ( 10.4 vs. 6.8%, P < 0.01). We also observed a trend towards increased insulin levels ( 10.06 +/- 6.66 vs. 7.45 +/- 5.88 mu IU/mL, P = 0.05), decreased QUICKI ( 0.36 +/- 0.06 vs. 0.39 +/- 0.07, P = 0.05) and decreased FMD ( 7.00 +/- 3.87 vs. 8.41 +/- 3.79%, P = 0.08). No other significant difference was observed. Conclusions NAFLD is frequent in obese women without any other health condition that could interfere with COC eligibility criteria, especially in those with PCOS. This should be considered when choosing the best contraceptive option. Copyright (C) 2012 ISUOG. Published by John Wiley & Sons, Ltd.

E' possibile giustificare moralmente l'obiezione di coscienza in campo medico?

Scopo di questa tesi di dottorato è stabilire se l’obiezione di coscienza in ambito medico sia moralmente giustificabile. Esistono essenzialmente tre tipi di rifiuto motivati dall’obiezione di coscienza (1) rifiuto di informare un paziente relativamente alle opzioni terapeutiche come ad esempio l’uso di un contraccettivo di emergenza o l’interruzione volontaria di gravidanza (2) rifiuto di rinviare un paziente che chiede un particolare intervento (o terapia) presso un collega non obiettore (3) rifiuto di svolgere in prima persona una certa attività richiesta dal paziente Per rispondere a questo interrogativo si è svolta un’analisi filosofico-morale dei principali argomenti utilizzati dalla letteratura su questo tema per giustificare o per negare un diritto morale all’obiezione di coscienza degli operatori sanitari. Il diritto degli operatori sanitari all’integrità morale e a non essere complici di attività ritenute immorali dev’essere infatti confrontato con il diritto dei pazienti ad avere un’assistenza sanitaria efficiente, a poter compiere scelte autonome riguardo alla propria salute e ad essere informati relativamente a tutte le opzioni terapeutiche disponibili. Nel corso dell’intero lavoro è stato dimostrato come suddetti diritti dei pazienti sono facilmente e frequentemente violati a causa dell’incidenza dell’obiezione di coscienza in ambito medico. L’analisi condotta nel corso del lavoro di tesi si concentra fondamentalmente su quattro importanti aspetti del problema quali diritto all’integrità morale dell’ operatore sanitario, obblighi professionali, cooperazione al male e laicità dello stato. Alla fine del lavoro di analisi si è giunti alla conclusione che: le obiezioni di tipo (1) e (2) non sono mai moralmente giustificabili perché comportano sempre una violazione dei diritti fondamentali del paziente. Le obiezioni di coscienza di tipo (3) sono moralmente accettabili solo quando non impongono un peso eccessivo al paziente, vale a dire quando il rinvio presso un collega non obiettore è veloce, sicuro e agevole. Tuttavia le condizioni ideali in cui vengono rispettati i criteri minimi di ammissibilità dell’obiezione di coscienza di tipo (3) non si verificano quasi mai nella realtà dei fatti (per ragioni ampiamente spiegate nel corso del lavoro), per cui tali obiezioni risultano in pratica solo raramente accettabili da un punto d vista morale.

Combinazioni androgeno-progestiniche per la contraccezione maschile

La contraccezione è un diritto fondamentale dell’uomo per il suo ruolo sulla salute, sulla qualità della vita e sul benessere della persona. La pianificazione familiare è uno dei principali strumenti che dà la possibilita’ a uomini e donne di condividere le proprie responsabilità sulla scelta contraccettiva e di decidere nella stessa misura della propria vita riproduttiva. Sin dall’introduzione della contraccezione femminile, la responsabilita’ della pianificazione familiare è ricaduta unicamente sulla donna. Attualmente infatti vi sono pochissimi metodi contraccettivi a disposizione degli uomini anche se vi e’ un rinnovato interesse da parte di questi ultimi nel sostenere le proprie partner nella scelta contraccettiva. Questo lavoro riassume i principali studi effettuati negli ultimi 10 allo scopo di sviluppare un contraccettivo che sia sicuro, efficace, reversibile e accettabile per l’uomo.

Serum glycodelin pattern during the menstrual cycle in healthy young women

OBJECTIVE: Glycodelin (PP14) is produced by the epithelium of the endometrium and its determination in the serum is used for functional evaluation of this tissue. Given the complex regulation and the combined contraceptive and immunosuppressive roles of glycodelin, the current lack of normal values for its serum concentration in the physiological menstrual cycle, derived from a large sample number, is a problem. We have therefore established reference values from over 600 sera. DESIGN: Retrospective study using banked serum samples. SETTING: University hospital. METHODS: Measurement of blood samples daily or every second day during one full cycle. MAIN OUTCOME MEASURES: Serum concentrations of glycodelin and normal values for every such one- or two-day interval were calculated. Late luteal phase glycodelin levels were compared with ovarian hormones. Follicular phase levels were compared with stimulated cycles from patients undergoing in vitro fertilization. RESULTS: Glycodelin concentrations were low around ovulation. Highest levels were observed at the end of the luteal phase; the glycodelin serum peak was reached 6-8 days after the one for progesterone. Late luteal glycodelin levels correlated negatively with the body mass index and positively with the progesterone level earlier in the secretory (mid-luteal) phase in the same woman. No associations with other ovarian hormones were observed. Follicular phase glycodelin levels were higher in the spontaneous than in the in vitro fertilization cycles. CONCLUSIONS: Normal values taken at two- or one-day intervals demonstrate the very late appearance of high serum glycodelin levels during the physiological menstrual cycle and their correlation with progesterone occurring earlier in the cycle.

Transformation of local medicinal knowledge in the Andean Highlands: Case studies from Peru and Bolivia

In the Andean highlands, indigenous environmental knowledge is currently undergoing major changes as a result of various external and internal factors. As in other parts of the world, an overall process of erosion of local knowledge can be observed. In response to this trend, some initiatives that adopt a biocultural approach aim at actively strengthening local identities and revalorizing indigenous environmental knowledge and practices, assuming that such practices can contribute to more sustainable management of biodiversity. However, these initiatives usually lack a sound research basis, as few studies have focused on the dynamics of indigenous environmental knowledge in the Andes and on its links with biodiversity management. Against this background, the general objective of this research project was to contribute to the understanding of the dynamics of indigenous environmental knowledge in the Andean highlands of Peru and Bolivia by investigating how local medicinal knowledge is socially differentiated within rural communities, how it is transformed, and which external and internal factors influence these transformation processes. The project adopted an actor-oriented perspective and emphasized the concept of knowledge dialogue by analyzing the integration of traditional and formal medicinal systems within family therapeutic strategies. It also aimed at grasping some of the links between the dynamics of medicinal knowledge and the types of land use systems and biodiversity management. Research was conducted in two case study areas of the Andes, both Quechua-speaking and situated in comparable agro-ecological production belts - Pitumarca District, Department of Cusco (Southern Peruvian Highlands) and the Tunari National Park, Department of Cochabamba (Bolivian inner-Andean valleys). In each case study area, the land use systems and strategies of 18 families from two rural communities, their environmental knowledge related to medicine and to the local therapeutic flora, and an appreciation of the dynamics of this knowledge were assessed. Data were collected through a combination of disciplinary and participatory action-research methods. It was mostly analyzed using qualitative methods, though some quantitative ethnobotanical methods were also used. In both case studies, traditional medicine still constitutes the preferred option for the families interviewed, independently of their age, education level, economic status, religion, or migration status. Surprisingly and contrary to general assertions among local NGOs and researchers, results show that there is a revival of Andean medicine within the younger generation, who have greater knowledge of medicinal plants than the previous one, value this knowledge as an important element of their way of life and relationship with “Mother Earth” (Pachamama), and, at least in the Bolivian case, prefer to consult the traditional healer rather than go to the health post. Migration to the urban centres and the Amazon lowlands, commonly thought to be an important factor of local medicinal knowledge loss, only affects people’s knowledge in the case of families who migrate over half of the year or permanently. Migration does not influence the knowledge of medicinal plants or the therapeutic strategies of families who migrate temporarily for shorter periods of time. Finally, economic status influences neither the status of people’s medicinal knowledge, nor families’ therapeutic strategies, even though the financial factor is often mentioned by practitioners and local people as the main reason for not using the formal health system. The influence of the formal health system on traditional medicinal knowledge varies in each case study area. In the Bolivian case, where it was only introduced in the 1990s and access to it is still very limited, the main impact was to give local communities access to contraceptive methods and to vaccination. In the Peruvian case, the formal system had a much greater impact on families’ health practices, due to local and national policies that, for instance, practically prohibit some traditional practices such as home birth. But in both cases, biomedicine is not considered capable of responding to cultural illnesses such as “fear” (susto), “bad air” (malviento), or “anger” (colerina). As a consequence, Andean farmers integrate the traditional medicinal system and the formal one within their multiple therapeutic strategies, reflecting an inter-ontological dialogue between different conceptions of health and illness. These findings reflect a more general trend in the Andes, where indigenous communities are currently actively revalorizing their knowledge and taking up traditional practices, thus strengthening their indigenous collective identities in a process of cultural resistance.

Everything is Bigger in Texas, Including the Latino Adolescent Pregnancy Rate: How Do We Eliminate the Epidemic of Latino Teen Pregnancy?

A commentary on Tortolero et al.'s article entitled, "Latino Teen Pregnancy in Texas: Prevalence, Prevention, and Policy."

Does Immediate Access to Birth Control Help Prevent Pregnancy? A Comparison of Onsite Provision Versus Off Campus Referral for Contraception at Two School-Based Clinics

PURPOSE: The purpose of this study was to assess the impact of different policies on access to hormonal contraception and pregnancy rates at two high school-based clinics. METHODS: Two clinics in high schools (Schools A and B), located in a large urban district in the southwest US, provide primary medical care to enrolled students with parental consent; the majority of whom have no health insurance coverage. The hormonal contraceptive dispensing policy of at School clinic A involves providing barrier, hormonal and emergency contraceptive services on site. School clinic B uses a referral policy that directs students to obtain contraception at an off-campus affiliated family planning clinic. Baseline data (age, race and history of prior pregnancy) on female students seeking hormonal contraception at the two clinics between 9/2008-12/2009 were extracted from an electronic administrative database (AHLERS Integrated System). Data on birth control use and pregnancy tests for each student was then tracked electronically through 3/31/2010. The outcomes measures were accessing hormonal contraception and positive pregnancy tests at any point during or after birth control use were started through 12/2009. The appointment keeping rate for contraceptive services and the overall pregnancy rates were compared between the two schools. In addition the pregnancy rates were compared between the two schools for students with and without a prior history of pregnancy. RESULTS: School clinic A: 79 students sought hormonal contraception; mean age 17.5 years; 68% were > 18 years; 77% were Hispanic; and 20% reported prior pregnancy. The mean duration of the observation period was 13 months (4-19 months). All 79 students received hormonal contraception (65% pill and 35% long acting progestin injection) onsite. During the observation period, the overall pregnancy rate was 6% (5/79); 4.7% (3/63) among students with no prior pregnancy. School clinic B: 40 students sought hormonal contraception; mean age 17.5 years; 52% > 18 years; 88 % were Hispanic; and 7.5% reported prior pregnancy. All 40 students were referred to the affiliated clinic. The mean duration of the observation period was 11.9 months (4-19 months). 50% (20) kept their appointment. Pills were dispensed to 85% (17/20) and 15% (3/20) received long acting progestin injection. The overall pregnancy rate was 20% (8/40); 21.6% (8/37) among students with no prior pregnancy. A significantly higher frequency of students seeking hormonal contraception kept their initial appointment for birth control at the school dispensing onsite contraception compared to the school with a referral policy for contraception (p<0.05). The pregnancy rate was significantly higher for the school with a referral policy for contraception compared to the school with onsite contraceptive services (p< 0.05). The pregnancy rate was also significantly higher for students without a prior history of pregnancy in the school with a referral policy for contraception (21.6%) versus the school with onsite contraceptive services (4.7%) (p< 0.05). CONCLUSION: This preliminary study showed that School clinic B with a referral policy had a lower appointment keeping rate for contraceptive services and a higher pregnancy rate than School clinic A with on-site contraceptive services. An on-site dispensing policy for hormonal contraceptives at high school-based health clinics may be a convenient and effective approach to prevent unintended first and repeat pregnancies among adolescents who seek hormonal contraception. This study has strong implications for reproductive health policy, especially as directed toward high-risk teenage populations.

Commentary on "A Tale of Two States"

While both California and Texas have experienced declines in teen birth rates over the past three decades, declines in California have been larger, particularly among Hispanic teens. Differences in state policies may have shaped this disparity, as suggested by Tortolero and her colleagues in their article “A Tale of Two States: What We Learn from California and Texas”. Fundamental differences exist between Texas and California in their approaches to sex education, access to family planning services for teens, and public-private partnerships. However, methodological challenges are present when drawing state comparisons, including the limitations of available public health data and the difficulty of disaggregating state characteristics from state policies. Based on their comparison of state data and policies, Tortolero and her colleagues issue sensible recommendations for reducing the teen birth rate in Texas. History suggests that state policies are most effective when political commitment is linked to scientifically effective approaches. Based on our understanding of the scientific literature, the most effective strategies for reducing rates of teen childbearing in Texas would be providing comprehensive school sexuality education and improving teen access to contraceptive services.

A case-control study of hepatitis C virus and its interaction with hepatitis B virus on the development of hepatocellular carcinoma in the USA

Objective. The aim of this study was to assess the independent risk of hepatitis C virus (HCV) infection in the development of hepatocellular carcinoma (HCC). The independent risk of hepatitis B virus (HBV), its interaction with hepatitis C virus and the association with other risk factors were examined.^ Methods. A hospital-based case-control study was conducted between January 1994 and December 1995. We enrolled 115 pathologically confirmed HCC patients and 230 nonliver cancer controls, who were matched by age ($\pm$5 years), gender, and year of diagnosis. Both cases and controls were recruited from The University of Texas M. D. Anderson Cancer Center at Houston. The risk factors were collected through personal interviews and blood samples were tested for HCV and HBV markers. Univariate and multivariate analyses were performed through conditional logistic regression.^ The prevalence of anti-HCV positive is 25.2% in HCC cases compared to 3.0% in controls. The univariate analysis showed that anti-HCV, HBsAg, alcohol drinking and cigarette smoking were significantly associated with HCC, however, family history of cancer, occupational chemical exposure, and use of oral contraceptive were not. Multivariate analysis revealed a matched odds ratio (OR) of 10.1 (95% CI 3.7-27.4) for anti-HCV, and an OR of 11.9 (95% CI 2.5-57.5) for HBsAg. However, dual infection of HCV and HBV had only a thirteen times increase in the risk of HCC, OR = 13.9 (95% CI 1.3-150.6). The estimated population attributable risk percent was 23.4% for HCV, 12.6% for HBV, and 5.3% for both viruses. Ever alcohol drinkers was positively associated with HCC, especially among daily drinkers, matched OR was 5.7 (95% CI 2.1-15.6). However, there was no significant increase in the risk of HCC among smokers as compared to nonsmokers. The mean age of HCC patients was significantly younger among the HBV(+) group and among the HCV(+)/HBV(+) group, when compared to the group of HCC patients with no viral markers. The association between past histories of blood transfusion, acupuncture, tattoo and IVDU was highly significant among the HCV(+) group and the HBV(+)/HCV(+) group, as compared to HCC patients with no viral markers. Forty percent of the HCC patients were pathologically or clinically diagnosed with liver cirrhosis. Anti-HCV(+) (OR = 3.6 95% CI 1.5-8.9) and alcohol drinking (OR = 2.7 95% CI 1.1-6.7), but not HBsAg, are the major risk factors for liver cirrhosis in HCC patients.^ Conclusion. Both hepatitis B virus and hepatitis C virus were independent risk factors for HCC. There was not enough evidence to determine the interaction between both viruses. Only daily alcoholic drinkers showed increasing risk for HCC development, as compared to nondrinkers. ^

Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis.

BACKGROUND Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC. METHODS AND FINDINGS Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15-49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37,124 women (43,613 woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84-1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study heterogeneity was mild (I2 < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use 0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (pinteraction = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship. CONCLUSIONS This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.

HIV testing and burden of HIV infection in black cancer patients in Johannesburg, South Africa: a cross-sectional study.

BACKGROUND HIV infection is a known risk factor for cancer but little is known about HIV testing patterns and the burden of HIV infection in cancer patients. We did a cross-sectional analysis to identify predictors of prior HIV testing and to quantify the burden of HIV in black cancer patients in Johannesburg, South Africa. METHODS The Johannesburg Cancer Case-control Study (JCCCS) recruits newly-diagnosed black cancer patients attending public referral hospitals for oncology and radiation therapy in Johannesburg . All adult cancer patients enrolled into the JCCCS from November 2004 to December 2009 and interviewed on previous HIV testing were included in the analysis. Patients were independently tested for HIV-1 using a single ELISA test . The prevalence of prior HIV testing, of HIV infection and of undiagnosed HIV infection was calculated. Multivariate logistic regression models were fitted to identify factors associated with prior HIV testing. RESULTS A total of 5436 cancer patients were tested for HIV of whom 1833[33.7% (95% CI=32.5-35.0)] were HIV-positive. Three-quarters of patients (4092 patients) had ever been tested for HIV. The total prevalence of undiagnosed HIV infection was 11.5% (10.7-12.4) with 34% (32.0-36.3) of the 1833 patients who tested HIV-positive unaware of their infection. Men >49 years [OR 0.49(0.39-0.63)] and those residing in rural areas [OR 0.61(0.39-0.97)] were less likely to have been previously tested for HIV. Men with at least a secondary education [OR 1.79(1.11-2.90)] and those interviewed in recent years [OR 4.13(2.62 - 6.52)] were likely to have prior testing. Women >49 years [OR 0.33(0.27-0.41)] were less likely to have been previously tested for HIV. In women, having children <5 years [OR 2.59(2.04-3.29)], hormonal contraceptive use [OR 1.33(1.09-1.62)], having at least a secondary education [OR:2.08(1.45-2.97)] and recent year of interview [OR 6.04(4.45-8.2)] were independently associated with previous HIV testing. CONCLUSIONS In a study of newly diagnosed black cancer patients in Johannesburg, over a third of HIV-positive patients were unaware of their HIV status. In South Africa black cancer patients should be targeted for opt-out HIV testing.

Interventions for hirsutism (excluding laser and photoepilation therapy alone)

BACKGROUND Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing disorder with a major impact on quality of life. The most common cause is polycystic ovary syndrome. There are many treatment options, but it is not clear which are most effective. OBJECTIVES To assess the effects of interventions (except laser and light-based therapies alone) for hirsutism. SEARCH METHODS We searched the Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), and five trials registers, and checked reference lists of included studies for additional trials. The last search was in June 2014. SELECTION CRITERIA Randomised controlled trials (RCTs) in hirsute women with polycystic ovary syndrome, idiopathic hirsutism, or idiopathic hyperandrogenism. DATA COLLECTION AND ANALYSIS Two independent authors carried out study selection, data extraction, 'Risk of bias' assessment, and analyses. MAIN RESULTS We included 157 studies (sample size 30 to 80) comprising 10,550 women (mean age 25 years). The majority of studies (123/157) were 'high', 30 'unclear', and four 'low' risk of bias. Lack of blinding was the most frequent source of bias. Treatment duration was six to 12 months. Forty-eight studies provided no usable or retrievable data, i.e. lack of separate data for hirsute women, conference proceedings, and losses to follow-up above 40%.Primary outcomes, 'participant-reported improvement of hirsutism' and 'change in health-related quality of life', were addressed in few studies, and adverse events in only half. In most comparisons there was insufficient evidence to determine if the number of reported adverse events differed. These included known adverse events: gastrointestinal discomfort, breast tenderness, reduced libido, dry skin (flutamide and finasteride); irregular bleeding (spironolactone); nausea, diarrhoea, bloating (metformin); hot flushes, decreased libido, vaginal dryness, headaches (gonadotropin-releasing hormone (GnRH) analogues)).Clinician's evaluation of hirsutism and change in androgen levels were addressed in most comparisons, change in body mass index (BMI) and improvement of other clinical signs of hyperandrogenism in one-third of studies.The quality of evidence was moderate to very low for most outcomes.There was low quality evidence for the effect of two oral contraceptive pills (OCPs) (ethinyl estradiol + cyproterone acetate versus ethinyl estradiol + desogestrel) on change from baseline of Ferriman-Gallwey scores. The mean difference (MD) was -1.84 (95% confidence interval (CI) -3.86 to 0.18).There was very low quality evidence that flutamide 250 mg, twice daily, reduced Ferriman-Gallwey scores more effectively than placebo (MD -7.60, 95% CI -10.53 to -4.67 and MD -7.20, 95% CI -10.15 to -4.25). Participants' evaluations in one study with 20 participants confirmed these results (risk ratio (RR) 17.00, 95% CI 1.11 to 259.87).Spironolactone 100 mg daily was more effective than placebo in reducing Ferriman-Gallwey scores (MD -7.69, 95% CI -10.12 to -5.26) (low quality evidence). It showed similar effectiveness to flutamide in two studies (MD -1.90, 95% CI -5.01 to 1.21 and MD 0.49, 95% CI -1.99 to 2.97) (very low quality evidence), as well as to finasteride in two studies (MD 1.49, 95% CI -0.58 to 3.56 and MD 0.40, 95% CI -1.18 to 1.98) (low quality evidence).Although there was very low quality evidence of a difference in reduction of Ferriman-Gallwey scores for finasteride 5 mg to 7.5 mg daily versus placebo (MD -5.73, 95% CI -6.87 to -4.58), it was unlikely it was clinically meaningful. These results were reinforced by participants' assessments (RR 2.06, 95% CI 0.99 to 4.29 and RR 11.00, 95% CI 0.69 to 175.86). However, finasteride showed inconsistent results in comparisons with other treatments, and no firm conclusions could be reached.Metformin demonstrated no benefit over placebo in reduction of Ferriman-Gallwey scores (MD 0.05, 95% CI -1.02 to 1.12), but the quality of evidence was low. Results regarding the effectiveness of GnRH analogues were inconsistent, varying from minimal to important improvements.We were unable to pool data for OCPs with cyproterone acetate 20 mg to 100 mg due to clinical and methodological heterogeneity between studies. However, addition of cyproterone acetate to OCPs provided greater reductions in Ferriman-Gallwey scores.Two studies, comparing finasteride 5 mg and spironolactone 100 mg, did not show differences in participant assessments and reduction of Ferriman-Gallwey scores (low quality evidence). Ferriman-Gallwey scores from three studies comparing flutamide versus metformin could not be pooled (I² = 62%). One study comparing flutamide 250 mg twice daily with metformin 850 mg twice daily for 12 months, which reached a higher cumulative dosage than two other studies evaluating this comparison, showed flutamide to be more effective (MD -6.30, 95% CI -9.83 to -2.77) (very low quality evidence). Data showing reductions in Ferriman-Gallwey scores could not be pooled for four studies comparing finasteride with flutamide as the results were inconsistent (I² = 67%).Studies examining effects of hypocaloric diets reported reductions in BMI, but which did not result in reductions in Ferriman-Gallwey scores. Although certain cosmetic measures are commonly used, we did not identify any relevant RCTs. AUTHORS' CONCLUSIONS Treatments may need to incorporate pharmacological therapies, cosmetic procedures, and psychological support. For mild hirsutism there is evidence of limited quality that OCPs are effective. Flutamide 250 mg twice daily and spironolactone 100 mg daily appeared to be effective and safe, albeit the evidence was low to very low quality. Finasteride 5 mg daily showed inconsistent results in different comparisons, therefore no firm conclusions can be made. As the side effects of antiandrogens and finasteride are well known, these should be accounted for in any clinical decision-making. There was low quality evidence that metformin was ineffective for hirsutism and although GnRH analogues showed inconsistent results in reducing hirsutism they do have significant side effects.Further research should consist of well-designed, rigorously reported, head-to-head trials examining OCPs combined with antiandrogens or 5α-reductase inhibitor against OCP monotherapy, as well as the different antiandrogens and 5α-reductase inhibitors against each other. Outcomes should be based on standardised scales of participants' assessment of treatment efficacy, with a greater emphasis on change in quality of life as a result of treatment.

The relationship between oral contraceptives and pelvic inflammatory disease: Policy implications and recommendations

One of the most widely accepted noncontraceptive benefits of oral contraceptive use is the reduction in the development of pelvic inflammatory disease (PID) and its sequelae in users. While much of the research over the past forty years has found an association between oral contraceptive use and reduced rates of PID [Senanayake, 1980], more recent studies have qualified and even challenged this widely held belief. [Henry-Suchet, 1997; Ness 1997; Ness, 2001] PID, an infection in the upper genital tract causing infertility and ectopic pregnancy, affects over one million women in the United States each year, exacting an enormous toll on women's reproductive and emotional health, as well as our economy. [CDC Factsheet, 2007] This thesis examines the public health implications of pelvic inflammatory disease and the use of oral contraceptives. Sixteen original studies are reviewed and analyzed, thirteen of which found a protective benefit with oral contraceptive use against PID and three more recent studies which found no protective benefit or association between oral contraceptive use and PID. Analysis of the research findings suggests a need for additional research, provider and patient education, and an increased government role in addressing the ongoing and significant public health concerns raised by current rates of Chlamydia- and gonorrheal-PID. ^

The association between maternal use of spermicides, condoms, intra-uterine devices or progesterone and major structural birth defects

Birth defects occur in 1 of every 33 babies born in the United States, and are the leading cause of infant death. Mothers using contraceptives that become pregnant may continue to use their contraceptives after their first missed menstrual period, thus exposing their baby in utero to the contraceptive product. Progesterone is also sometimes prescribed during the first trimester of pregnancy to mothers with a history of miscarriages or infertility problems. To ensure the safety of these products, it is important to investigate whether there is an increased occurrence of babies born with birth defects to mothers using various contraceptive methods or progesterone in early pregnancy. Using data from the National Birth Defects Prevention Study (NBDPS), an ongoing multi-state, population based case-control study, this study assessed maternal exposures to IUDs, spermicides, condoms and progesterone in early pregnancy. ^ Progesterone used for threatened miscarriage during the first three months of pregnancy was associated with an increased occurrence of hypoplastic left heart (adjusted odds ratios (OR) 2.24, 95% CI 1.13-4.21), perimembranous ventricular septal defects (OR 1.64, 95% CI 1.10-2.41), septal associations (OR 2.52, 95% CI 1.45-4.24), esophageal atresia (OR 1.82, 95% CI 1.04-3.08), and hypospadias (OR 2.12, 95% CI 1.41-3.18). Mothers using progesterone for injectable contraception had increased (OR > 2.5), but insignificant odds ratios for anencephaly, septal associations, small intestinal atresias and omphalocel. Progesterone used for fertility was not associated with an increased occurrence of any birth defects examined. ^ Mothers using progesterone for fertility assistance and threatened miscarriage were very similar with respect to their demographics and pregnancy history. They also both reported similar types of progesterone. Thus, if progesterone was a causal risk factor for birth defects we would have expected to observe similar increases in risk among mothers using progesterone for both indications. Because we predominantly observed increased associations among mothers using progesterone for threatened miscarriage but not fertility assistance, it is possible the increased associations we observed were confounded by indication (i.e. progesterone was administered for vaginal bleeding which occurred as a sequelae to the formation of a congenital anomaly. ^ No significant increased associations were observed between maternal spermicide use during pregnancy and 26 of 27 types of structural malformations. While multiple statistical tests were performed we observed first trimester maternal spermicide use to be associated with a significant increased occurrence of perimembranous ventricular septal defects (OR 2.21, 95% CI 1.16-4.21). A decreased occurrence (OR < 1.0) was observed for several categories of birth defects among mothers who conceived in the first cycle after discontinuing the use of spermicides (22 of 28) or male condoms (23 of 33). ^ Overall the percent of IUD use was similar between mothers of controls and mothers of all cases in aggregate (crude OR 1.05, 95% CI 0.61-1.84). Power was limited to detect significant associations between IUD use and birth defects, however mothers using an IUD in the month immediately prior to conception or during pregnancy were not associated with an increase of birth defects. Limb defects and amniotic band sequence previously reported to be associated with IUD use during pregnancy were not found to occur among any mothers reporting the use of an IUD during pregnancy.^

Hormonal exposure and risk of pancreatic cancer in the United States

Background. In the United States, the incidence of pancreatic cancer has increased; more than 37,000 new cases of pancreatic cancer were diagnosed in the year 2007. Overall, the five-year survival rate is about 5% and pancreatic cancer ranks the fourth leading cause of cancer-related mortality among men and women. Despite the observed progress in cancer diagnosis and treatment, pancreatic cancer remains an unresolved significant public health problem in the United States. Familial pancreatic cancer has been confirmed to be responsible for approximately 10% of pancreatic cancer cases. However, 90% are still without known inherited predisposition. Until now, the role of oral contraceptive pills (OCPs) and hormonal replacement therapy (HRT) among women with pancreatic cancer remain unclear. We examined the association of exogenous hormonal uses in US women with risk of pancreatic cancer. ^ Methods. This was an active hospital-based case-control study which is conducted at the department of gastrointestinal medical oncology in The University of Texas M.D. Anderson Cancer Center. Between January 2005 and December 2007, a total of 287 women with pathologically confirmed pancreatic cancer (cases) and 287 healthy women (controls) were included in this investigation. Both cases and controls were frequency matched by age and race. Information about the use of hormonal contraceptives and hormonal replacement therapy (HRT) preparations as well as information about several risk factors of pancreatic cancer were collected by personal interview. Univariate and multivariate analyses were performed in this study to analyze the data. ^ Results. We found a statistical significant protective effect for use of exogenous hormone preparations on pancreatic cancer development (adjusted odds ratio [AOR], 0.4; 95% confidence interval [CI], 0.2–0.8). In addition, a 40% reduction in pancreatic cancer risk was observed among women who ever used any of the contraceptive methods including oral contraceptive pills (AOR, 6; 95% CI, 0.4–0.9). ^ Conclusions. Consistent with previous studies, the use of exogenous hormone preparations including oral contraceptive pills may confers a protective effect for pancreatic cancer development. More studies are warranted to explore for the underlying mechanism of such protection.^