ABSTRACT
BACKGROUND: There is evolving evidence that vitamin D insufficiency may contribute to food allergy, but findings vary between populations. Lower vitamin D-binding protein (DBP) levels increase the biological availability of serum vitamin D. Genetic polymorphisms explain almost 80% of the variation in binding protein levels. OBJECTIVE: We sought to investigate whether polymorphisms that lower the DBP could compensate for adverse effects of low serum vitamin D on food allergy risk. METHODS: From a population-based cohort study (n = 5276) we investigated the association between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and food allergy at age 1 year (338 challenge-proven food-allergic and 269 control participants) and age 2 years (55 participants with persistent and 50 participants with resolved food allergy). 25(OH)D3 levels were measured using liquid chromatography-tandem mass spectrometry and adjusted for season of blood draw. Analyses were stratified by genotype at rs7041 as a proxy marker of DBP levels (low, the GT/TT genotype; high, the GG genotype). RESULTS: Low serum 25(OH)D3 level (≤50 nM/L) at age 1 years was associated with food allergy, particularly among infants with the GG genotype (odds ratio [OR], 6.0; 95% CI, 0.9-38.9) but not in those with GT/TT genotypes (OR, 0.7; 95% CI, 0.2-2.0; P interaction = .014). Maternal antenatal vitamin D supplementation was associated with less food allergy, particularly in infants with the GT/TT genotype (OR, 0.10; 95% CI, 0.03-0.41). Persistent vitamin D insufficiency increased the likelihood of persistent food allergy (OR, 12.6; 95% CI, 1.5-106.6), particularly in those with the GG genotype. CONCLUSIONS: Polymorphisms associated with lower DBP level attenuated the association between low serum 25(OH)D3 level and food allergy, consistent with greater vitamin D bioavailability in those with a lower DBP level. This increases the biological plausibility of a role for vitamin D in the development of food allergy.
Subject(s)
Calcifediol/blood , Food Hypersensitivity/blood , Food Hypersensitivity/genetics , Genetic Association Studies , Polymorphism, Single Nucleotide , Vitamin D-Binding Protein/genetics , Adolescent , Adult , Alleles , Child , Child, Preschool , Cohort Studies , Dietary Supplements , Female , Follow-Up Studies , Food Hypersensitivity/epidemiology , Genotype , Humans , Infant , Male , Odds Ratio , Population Surveillance , Risk , Seasons , Young AdultABSTRACT
INTRODUCTION: Colorectal cancer (CRC) is the second most common cancer. One-third of these cancers occur in the rectum. Treatment of rectal cancer involves surgery with/without radiotherapy and chemotherapy. Surgery is undertaken to prevent damage to the nerves controlling bladder, bowel, and sexual organs, whether this translates into preservation of urinary and fecal continence and sexual function and, ultimately, quality of life (QoL) is not known. AIM: The aim of this review was to summarize the literature regarding the impact of treatment for rectal cancer on bladder and bowel continence, sexual function and QoL in women. MAIN OUTCOME MEASURES: A comprehensive review of the current literature on sexual function, incontinence and wellbeing in women after treatment for rectal cancer highlighting prevalence rates, trial design, and patient population. METHODS: We conducted a systematic search of the literature using A systematic search of the literature using Medline (Ovid, 1946-present) and PubMed (1966-2011) for English-language studies that included the following search terms: "colorectal cancer," or "rectal cancer," or "rectal neoplasm," and "sexual function," or "sexual dysfunction," or "wellbeing," or "QoL," or "urinary or fecal incontinence." RESULTS: Although around 1/3 of women aged 50 to 70 years report lack of sexual desire, sexual function problems after treatment for rectal cancer are in the order of 60% among women. QoL improves with length of survival. Urinary and fecal incontinence are ongoing concerns for many women after treatment with rates up to 60%. CONCLUSION: There is a gap in our knowledge of the effects of rectal cancer and its treatment on urinary and fecal continence, sexual function and QoL in women. There is a need for studies of sufficient size and duration to gain a better understanding of the disease and its management and the long-term effects on these parameters. This information is needed to develop preventative health care plans for women treated for rectal cancer that target those most at risk for these adverse outcomes.
Subject(s)
Fecal Incontinence/psychology , Postoperative Complications/psychology , Quality of Life/psychology , Sexual Dysfunction, Physiological/psychology , Urinary Incontinence/psychology , Aged , Cross-Sectional Studies , Fecal Incontinence/epidemiology , Female , Humans , Middle Aged , Postoperative Complications/epidemiology , Risk Factors , Sexual Dysfunction, Physiological/epidemiology , Sexual Dysfunctions, Psychological/epidemiology , Sexual Dysfunctions, Psychological/psychology , Urinary Incontinence/epidemiologyABSTRACT
OBJECTIVE: To explore the beliefs held by breast cancer (BC) survivors about the factors that contribute to the development of their BC. METHODS: The BUPA Health Foundation Health and Well-being after Breast Cancer Study is a prospective cohort study of 1684 women recruited within 12 months of their first diagnosis with invasive BC. Participants completed an enrollment questionnaire (EQ), first follow-up questionnaire (FQ1) and a second follow-up questionnaire (FQ2), 12 months and 24 months post-EQ, respectively. In the FQ2, women were asked whether they believed anything contributed to the development of their BC and whether they had made lifestyle changes since the FQ1. Well-being was assessed at the FQ2 using the psychological general well-being index (PGWB). RESULTS: In total, 1496/1684 women completed the FQ2 and 43.5% reported belief in a factor that may have contributed to their developing BC. These women were more likely to be younger (p<0.0001) and educated beyond high school (p<0.0001). Stress (58.1%) was the most common reason given, followed by previous use of hormone therapy (17.0%) and a family history of any cancer (9.8%). Women who believed stress contributed to their BC had lower PGWB scores than other study participants (70.9 ± 16.1, n = 361 versus 77.3 ± 14.9, n = 1071, mean difference = 6.4, 95% CI: 4.6-8.2 p<0.0001) and were more likely to have made lifestyle changes since their BC diagnosis. CONCLUSIONS: Many women with BC believe that stress has contributed to their condition. Women who held this belief were more likely to adopt strategies to reduce stress than those who did not.
Subject(s)
Breast Neoplasms/psychology , Health Behavior , Health Knowledge, Attitudes, Practice , Survivors/psychology , Adult , Age Distribution , Aged , Australia , Breast Neoplasms/diagnosis , Breast Neoplasms/etiology , Female , Follow-Up Studies , Humans , Middle Aged , Prospective Studies , Risk Factors , Socioeconomic Factors , Stress, Psychological , Surveys and QuestionnairesABSTRACT
INTRODUCTION: Breast cancer (BC) remains the most common non-skin cancer in women and an increasing number are living as BC survivors. AIM: The aim of this article is to evaluate the impact of the first diagnosis of invasive BC and its treatment, menopausal symptoms, and body image on sexual function. METHODS: The BUPA Foundation Health and Wellbeing after Breast Cancer Study is a prospective cohort study of 1,684 women recruited within 12 months of their first diagnosis with invasive BC. Each participant completed an enrollment questionnaire (EQ) and first follow-up questionnaire (FQ1) 12 months post-EQ. MAIN OUTCOME MEASURE: Sexual function was evaluated by the Menopause-Specific Quality of Life Questionnaire embedded within the FQ1. RESULTS: Of the 1,011 women in the analyses, 70% experienced sexual function problems and 77% reported vasomotor symptoms. Women experiencing sexual function problems were postmenopausal (P = 0.02), experienced vasomotor symptoms (P < 0.01), and used aromatase inhibitors (P = 0.03). Women with vasomotor symptoms were twice as likely to experience sexual function problems (odds ratio [OR] 1.93, 95% confidence interval [CI] 141, 2.63; P < 0.001). This association was more extreme for women on aromatase inhibitors (OR 3.49, 95% CI 1.72, 7.09; P = 0.001) but did not persist in women not using endocrine therapies (OR 1.41, 95% CI 0.84, 2.36; P = 0.19). Women on aromatase inhibitors were more likely to report sexual function problems (OR 1.50, 95% CI 1.0, 2.2, P = 0.04) and women with body image issues were 2.5 times more likely to report sexual function problems (OR 2.5 95% CI 1.6, 3.7, P < 0.001). Women using tamoxifen were not more likely to experience sexual function problems (OR 1.1, 95% CI 0.8, 1.5, P = 0.6); however, women with body image issues were twice as likely to experience sexual function problems (OR 2.1, 95% CI 1.5, 3.0, P < 0.001). CONCLUSION: Seventy percent of partnered BC survivors less than 70 experienced sexual function problems. Sexual problems are related to the use of aromatase inhibitors which can exacerbate menopausal symptoms.
Subject(s)
Breast Neoplasms/complications , Breast Neoplasms/psychology , Sexual Dysfunction, Physiological/etiology , Sexuality , Adult , Aged , Antineoplastic Agents/adverse effects , Aromatase Inhibitors/adverse effects , Body Image , Estrogen Replacement Therapy , Female , Follow-Up Studies , Humans , Logistic Models , Mastectomy/psychology , Middle Aged , Multivariate Analysis , Quality of Life , Survivors/psychology , Tamoxifen/adverse effects , VictoriaABSTRACT
INTRODUCTION: Dehydroepiandrosterone (DHEA) and its sulfate DHEAS, which are the most abundant steroids in women, decline with age. We have shown association between low sexual function and low circulating DHEAS levels in women. AIM: The aim of this study was to evaluate whether restoration of circulating DHEA levels in postmenopausal women to the levels seen in young individuals improves sexual function. METHODS: Ninety-three postmenopausal women not using concurrent estrogen therapy were enrolled in a 52-week randomized, double-blind, placebo controlled trial and received either DHEA 50 mg or placebo (PL) daily. MAIN OUTCOME MEASURES: Efficacy was assessed through 26 weeks. The main outcome measures were the change in total satisfying sexual events (SSE) and the change in the Sabbatsberg Sexual Self-Rating Scale (SSS) total score. Secondary measures were the Psychological General Well-Being Questionnaire (PGWB), and the Menopause-Specific Quality of Life Questionnaire (MENQOL). Hormonal levels, adverse events (AEs), serious adverse events (SAEs) and clinical labs were evaluated over 52 weeks. RESULTS: Eighty-five participants (91%) were included in the 26-week efficacy analysis. There were no significant differences between the DHEA and PL groups in the change in total SSE per month or the SSS, PGWB, and MENQOL change scores. Overall AE reports and number of withdrawals as a result of AEs were similar in both groups; however more women in the DHEA group experienced androgenic effects of acne and increased hair growth. CONCLUSIONS: In this study treatment of postmenopausal women with low sexual desire with 50 mg/day DHEA resulted in no significant improvements in sexual function over PL therapy over 26 weeks.
Subject(s)
Adjuvants, Immunologic/therapeutic use , Dehydroepiandrosterone/therapeutic use , Mental Health , Patient Satisfaction , Postmenopause/drug effects , Quality of Life , Sexual Dysfunctions, Psychological/drug therapy , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/blood , Administration, Oral , Adult , Aged , Analysis of Variance , Climacteric/drug effects , Dehydroepiandrosterone/administration & dosage , Dehydroepiandrosterone/blood , Double-Blind Method , Female , Health Status Indicators , Humans , Linear Models , Middle Aged , Psychometrics , Risk , Sexual Dysfunctions, Psychological/epidemiology , Surveys and QuestionnairesABSTRACT
Data collected from 317 heroin users who participated in four studies that were included in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence were analysed to examine predictors of follow-up difficulty and whether follow-up difficulty was related to heroin use outcomes. Participants who were no longer receiving treatment were more difficult to contact and more likely to be lost to follow-up. Participants treated in general practice settings were also more difficult to contact and more likely to be lost to follow-up than participants treated at specialist clinics. Contact difficulty among followed-up participants (either in or out of treatment) was unrelated to heroin use outcomes. The 21% of participants who were followed-up with just one contact attempt reported 20.0 heroin-free days in the previous month, increasing only slightly to 20.9 based on the 70% of participants eventually contacted after up to 20 attempts. The study examined three methods for imputing missing heroin use outcome data and concluded that imputation of missing outcome data by inserting corresponding baseline data may be too conservative.
Subject(s)
Data Collection , Heroin Dependence/epidemiology , Adolescent , Adult , Australia/epidemiology , Bias , Female , Follow-Up Studies , Heroin Dependence/drug therapy , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
INTRODUCTION: Postnatal vitamin D supplementation may be associated with a reduction in IgE-mediated food allergy, lower respiratory tract infections and improved bone health. Countries in the Northern hemisphere recommend universal infant vitamin D supplementation to optimise early vitamin D levels, despite the absence of large trials proving safety or efficacy for any disease outcome. With the aim of determining the clinical and cost-effectiveness of daily vitamin D supplementation in breastfed infants from age 6-8 weeks to 12 months of age, we have started a double-blind, randomised, placebo-controlled trial of daily 400 IU vitamin D supplementation during the first year of life, VITALITY. METHODS ND ANALYSIS: Infants (n=3012) who are fully breastfed and not receiving vitamin D supplementation will be recruited at the time of their first immunisation, from council-led immunisation clinics throughout metropolitan Melbourne, Australia. The primary outcome is challenge-proven food allergy at 12 months of age. Secondary outcomes are food sensitisation (positive skin prick test), number of lower respiratory infections (through hospital linkage), moderately-severe and persistent eczema (by history and examination) and vitamin D deficiency (serum vitamin D <50 nmol/L) at age 12 months. The trial is underway and the first 130 participants have been recruited. ETHICS AND DISSEMINATION: The VITALITY study is approved by the Royal Children's Hospital (RCH) Human Research Ethics Committee (#34168). Outcomes will be disseminated through publication and will be presented at scientific conferences. TRIAL REGISTRATION NUMBERS: ANZCTR12614000334606 and NCT02112734; pre-results.
Subject(s)
Breast Feeding , Dietary Supplements , Eczema/drug therapy , Food Hypersensitivity/prevention & control , Respiratory Tract Infections/prevention & control , Vitamin D Deficiency/drug therapy , Vitamin D/therapeutic use , Clinical Protocols , Double-Blind Method , Humans , Infant , Research Design , Vitamins/therapeutic useABSTRACT
AIMS: The present study aimed to compare the efficacy of levo-alpha-acetylmethadol (LAAM) and methadone, as measured by retention in treatment and heroin use, in a randomized trial conducted under naturalistic conditions. SETTING: This study is the first randomized trial comparing LAAM with methadone in the primary care setting. Participants were recruited through 29 medical practitioners working in specialist and generalist settings in Australia. PARTICIPANTS: Existing methadone maintenance patients, aged 18 years and over and able to give informed consent, were randomized to receive either LAAM or methadone. A total of 93 patients participated. INTERVENTION: After being trained in the use of LAAM, existing methadone prescribers were then able to determine an individually tailored treatment regimen for each patient. The trial was an open-label study. Methadone and LAAM dosing was supervised through local community pharmacies. Participation in ancillary services (e.g. counselling) was optional for all patients. The treatment period for the trial was 12 months. MEASUREMENTS: Baseline, 3-, 6- and 12-month interviews were conducted. Outcome measures were retention in treatment, self-reported heroin use and serious adverse events. FINDINGS: There were no significant differences between LAAM and methadone on retention in treatment, nor heroin use. There was a trend for LAAM patients to have lower heroin use than methadone patients. Of the seven serious adverse events in the LAAM group, three were not drug-related. There were two dosing errors. CONCLUSIONS: This study demonstrates (a) the efficacy of LAAM as a treatment for heroin dependence, and (b) the capacity for LAAM to be effectively delivered in primary care settings by trained general practitioners and pharmacists. The next challenge is to resolve outstanding safety concerns with LAAM.
Subject(s)
Heroin Dependence/rehabilitation , Methadone/therapeutic use , Methadyl Acetate/therapeutic use , Narcotics/therapeutic use , Adult , Australia , Family Practice , Female , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Treatment OutcomeABSTRACT
OBJECTIVE: We investigated the prevalence and severity of menopausal symptoms, nearly 6 years from diagnosis, in women who had not experienced recurrent breast cancer or a new primary breast cancer (active disease) and were no longer taking oral adjuvant endocrine therapy (OAET). METHODS: A total of 1,683 women recruited within 12 months of diagnosis with invasive breast cancer completed an enrollment questionnaire and five annual follow-up questionnaires. Only women who had never reported active disease and were not taking OAET at their fifth follow-up were included in the analysis. Women previously recruited to a study of sex steroid levels provided community control data. Menopausal symptoms were assessed with the Menopause-Specific Quality of Life Questionnaire (MenQOL). RESULTS: Eight hundred forty-three women without active disease and not taking OAET completed the fifth follow-up questionnaire, on average, 5.8 years after diagnosis. Most had stage I (59.5%) and hormone receptor-positive disease (77.9%) at diagnosis and were postmenopausal (92.8%). Those aged 50 to 59 years were more likely to report any symptoms (P = 0.01) and more severe symptoms (P < 0.001) than older and younger women. There was no independent impact of chemotherapy on MenQOL vasomotor and sexual domain scores. Women with breast cancer had significantly higher vasomotor domain (P ≤ 0.002) and sexual domain (P ≤ 0.004) scores than community controls. CONCLUSIONS: Vasomotor and sexual symptoms are highly prevalent in breast cancer survivors and are not simply a function of OAET or chemotherapy. Given the adverse impact of these symptoms, effective interventions are needed to alleviate them in women who have completed their breast cancer treatment.
Subject(s)
Breast Neoplasms/physiopathology , Menopause/physiology , Survivors , Aged , Australia/epidemiology , Breast Neoplasms/chemistry , Chemotherapy, Adjuvant , Cohort Studies , Female , Follow-Up Studies , Hot Flashes/epidemiology , Humans , Menopause/psychology , Middle Aged , Prospective Studies , Quality of Life , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Reproductive Health , Surveys and Questionnaires , Vasomotor System/physiopathologyABSTRACT
BACKGROUND: Management of older women with breast cancer (BC) is challenging, as age-related comorbidities may limit treatment. We present 5-year follow-up data from women aged 70 years or older (70+), at the time of diagnosis of their BC, compared with younger women (<70 years). METHODS: Data is from an Australian cohort study of women with their first episode of invasive BC (Bupa study). Participants completed an enrollment questionnaire (EQ) within 12 months of diagnosis and annual follow-up questionnaires (FQ) for 5 years (FQ1-5). Data collected included details of the BC and its treatment. Psychological wellbeing was measured by the Psychological General Wellbeing Index (PGWB). RESULTS: At diagnosis, 274 (16%) women were aged 70+ and of them, 90% were aged 70-79 years. Compared with women aged <70 years, the women aged 70+ were less likely to have positive nodes, they were less likely to receive radiotherapy and chemotherapy and were more likely to have pre-existing cardiovascular morbidities. By FQ5 women aged 70+ were less likely to be taking oral adjuvant endocrine therapy (OAET) and were more likely to have died from causes other than BC. At FQ5, women 70+ reported less anxiety and better self-control. CONCLUSIONS: Women aged 70+, compared to <70 years, had less advanced disease, received radiation and chemotherapy less often, were more likely to have cardiovascular disease at the time of diagnosis, were less likely to be taking OAET at the 5-year assessment, and were more likely to die of causes other than breast cancer.
Subject(s)
Breast Neoplasms/psychology , Breast Neoplasms/therapy , Geriatric Assessment , Quality of Life , Aged , Australia , Breast Neoplasms/diagnosis , Combined Modality Therapy/methods , Female , Follow-Up Studies , Humans , Neoplasm Invasiveness , Prospective Studies , Psychological Tests , Psychometrics , Reproducibility of Results , Surveys and QuestionnairesABSTRACT
PURPOSE: The aim of our study was to establish the prevalence of breast pain persisting 5 years after the initial treatment of breast cancer (BC) and the relationship between those persistent symptoms and general well-being. METHODS: The study involved women from Victoria, Australia, who had survived at least 5 years from diagnosis, remained free from recurrence or new BC and completed the fifth annual follow-up questionnaire. Analysis involved both multivariable logistic and linear regression. RESULTS: Of 1,205 women, 45 % reported breast pain which persisted for at least 3 months following initial treatment, and of these, 80 % reported pain persisting for at least 5 years. The factor contributing most to the likelihood of persistent breast pain was current lymphedema; however, a full multivariable model explained <10 % of the likelihood of breast pain persisting for 5 years. The presence of breast pain at 5 years was associated with only a modest reduction in general well-being. CONCLUSIONS: Breast pain persisting for at least 5 years after treatment for BC is common. As the pain is largely unexplained by factors associated with the characteristics of the cancer or its treatment, the contribution of patient expectations to persistent breast pain may be considerable. IMPLICATIONS FOR CANCER SURVIVORS: Where persistent pain occurs, referral for the management of pain and, where appropriate, lymphedema is warranted.
Subject(s)
Breast Neoplasms/complications , Carcinoma, Ductal, Breast/complications , Lymphedema/physiopathology , Mastodynia/etiology , Antineoplastic Agents, Hormonal/adverse effects , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Ductal, Breast/surgery , Chemotherapy, Adjuvant/adverse effects , Combined Modality Therapy , Female , Humans , Lymph Node Excision/adverse effects , Lymphedema/etiology , Mastectomy/adverse effects , Mastodynia/physiopathology , Mastodynia/psychology , Pain Clinics/statistics & numerical data , Pain Management , Pain, Postoperative/etiology , Pain, Postoperative/physiopathology , Pain, Postoperative/psychology , Paresthesia/etiology , Paresthesia/physiopathology , Paresthesia/psychology , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Quality of Life , Radiotherapy, Adjuvant/adverse effects , Surveys and Questionnaires , Survivors/psychology , Time FactorsABSTRACT
We aimed to investigate the relationship between genetic and environmental exposure and vitamin D status at age one, stratified by ethnicity. This study included 563 12-month-old infants in the HealthNuts population-based study. DNA from participants' blood samples was genotyped using Sequenom MassARRAY MALDI-TOF system on 28 single nucleotide polymorphisms (SNPs) in six genes. Using logistic regression, we examined associations between environmental exposure and SNPs in vitamin D pathway and filaggrin genes and vitamin D insufficiency (VDI). VDI, defined as serum 25-hydroxyvitamin D3(25(OH)D3) level ≤50nmol/L, was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Infants were stratified by ethnicity determined by parent's country of birth. Infants formula fed at 12 months were associated with reduced odds of VDI compared to infants with no current formula use at 12 months. This association differed by ethnicity (Pinteraction=0.01). The odds ratio (OR) of VDI was 0.29 for Caucasian infants (95% CI, 0.18-0.47) and 0.04 for Asian infants (95% CI, 0.006-0.23). Maternal vitamin D supplementation during pregnancy and/or breastfeeding were associated with increased odds of infants being VDI (OR, 2.39; 95% CI, 1.11-5.18 and OR, 2.5; 95% CI, 1.20-5.24 respectively). Presence of a minor allele for any GC SNP (rs17467825, rs1155563, rs2282679, rs3755967, rs4588, rs7041) was associated with increased odds of VDI. Caucasian infants homozygous (AA) for rs4588 had an OR of 2.49 of being associated with VDI (95% CI, 1.19-5.18). In a country without routine infant vitamin D supplementation or food chain fortification, formula use is strongly associated with a reduced risk of VDI regardless of ethnicity. There was borderline significance for an association between filaggrin mutations and VDI. However, polymorphisms in vitamin D pathway related genes were associated with increased likelihood of being VDI in infancy.
Subject(s)
Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/etiology , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics , Asian People/genetics , Breast Feeding , Cholestanetriol 26-Monooxygenase/genetics , Cytochrome P450 Family 2 , Diet , Dietary Supplements , Environment , Environmental Exposure , Female , Filaggrin Proteins , Humans , Infant , Infant Formula , Intermediate Filament Proteins/genetics , Odds Ratio , Polymorphism, Single Nucleotide , Pregnancy , Receptors, Calcitriol/genetics , Seasons , Ultraviolet Rays , Victoria/epidemiology , Vitamin D/administration & dosage , Vitamin D-Binding Protein/genetics , Vitamin D3 24-Hydroxylase/genetics , White People/geneticsABSTRACT
Vaginal atrophy is a common symptom of postmenopausal estrogen deficiency and can present as dryness, irritation, infection and dyspareunia and can affect sexual function and quality of life. Currently vaginal atrophy is treated with the intravaginal application of preparations containing estradiol or estriol, which are both effective and safe. It has been proposed that intravaginally administered dehydroepiandrosterone (DHEA) can be used to treat vaginal atrophy. DHEA and its sulphate DHEAS are the most abundant circulating sex steroid hormones in women, and provide a large precursor reservoir for the intracellular production of androgens and estrogens in non-reproductive tissues. Levels of DHEA and DHEAS decline with age. Although there is some evidence to support the use of intravaginal DHEA for postmenopausal women with symptoms of vaginal atrophy, independent studies are required to confirm this. In addition studies regarding the effects of vaginal DHEA on sexual function in women without vaginal atrophy are needed. Given that the efficacy and long term safety of low dose vaginal estradiol and estriol therapy is well established and that vaginal estrogen requires application of 2-3 times a week, rather than daily dosing; the benefit of daily vaginal DHEA over estrogen also needs to be considered as women may find it unpalatable to adhere to daily dosing with a cream preparation.
Subject(s)
Dehydroepiandrosterone/administration & dosage , Vagina/pathology , Vaginal Diseases/drug therapy , Administration, Intravaginal , Atrophy/drug therapy , Endometrium/drug effects , Female , Humans , Randomized Controlled Trials as Topic , Vaginal Diseases/pathologyABSTRACT
CONTEXT: It has been proposed that because dehydroepiandrosterone (DHEA) and its sulfate, DHEAS, are important precursors for estrogen and androgen production, treatment with DHEA is a physiologically based strategy for the alleviation of hormone deficiency symptoms in postmenopausal women. We have summarized the physiology of DHEA in women and reviewed the findings from randomized controlled trials (RCT) of the effects of DHEA therapy in postmenopausal women with normal adrenal function. EVIDENCE ACQUISITION: We reviewed the medical literature for key papers investigating DHEA physiology and RCT of the use of DHEA in postmenopausal women through November 2010. The focus was on sexual function, well-being, metabolic parameters, and cognition as study endpoints. EVIDENCE SYNTHESIS: Although cross-sectional studies have indicated a link between low DHEA levels and impaired sexual function, well-being, and cognitive performance in postmenopausal women, placebo-controlled RCT do not show benefits of oral DHEA for any of these outcomes or favorable effects on lipids and carbohydrate metabolism. CONCLUSIONS: Taken together, findings from this review of the published literature of studies do not support the use of DHEA in postmenopausal women at this time.
Subject(s)
Dehydroepiandrosterone/therapeutic use , Hormone Replacement Therapy , Postmenopause , Cognition/drug effects , Dehydroepiandrosterone/pharmacology , Female , Humans , Randomized Controlled Trials as Topic , Sexual Dysfunctions, Psychological/drug therapyABSTRACT
BACKGROUND: Dehydroepiandrosterone (DHEA) and its sulphate DHEAS are the most abundant sex steroids in women and provide a large reservoir of precursors for the intracellular production of androgens and estrogens in non-reproductive tissues. Levels of DHEA and DHEAS decline with age. It has been proposed that restoring the circulating levels of these steroids to those found in young women may have anti-aging effects and improve sexual function and wellbeing in postmenopausal women. AIM: To review the published literature for the efficacy of DHEA therapy data regarding safety. METHODS: A systematic literature search of MEDLINE (Ovid) and Pub-Med (1966 to November 2009) for original studies that included any of the terms dehydroepiandrosterone, DHEA or DHEAS, sexual function, wellbeing, women and metabolic parameters of interest. RESULTS: Overall the interpretation of the data was limited by inadequate sample size and short treatment duration of available studies with inconsistent results. The more recent randomized controlled trials however do not support a benefit of oral DHEA therapy for women. A possible benefit that emerged is that vaginally administered DHEA may improve vaginal atrophy with concomitant improvements in sexual function in women who are estrogen deficient due to menopause. The potential value of oral DHEA therapy for postmenopausal women is called into question.
Subject(s)
Dehydroepiandrosterone/physiology , Dehydroepiandrosterone/therapeutic use , Postmenopause/physiology , Sexual Dysfunction, Physiological/drug therapy , Carbohydrate Metabolism/drug effects , Female , Humans , Lipid Metabolism/drug effectsABSTRACT
Exposure to postmenopausal hormone therapy (HT) may affect the stage, histological type, and hormone receptor (HR) status of invasive breast cancer at the time of diagnosis. One thousand six hundred eighty-four women with newly diagnosed first invasive breast cancer were recruited to the "MBF Foundation Health and Wellbeing after Breast Cancer Study." Women using systemic HT estrogen (E) or E combined with progesterone (P) at the time of diagnosis of breast cancer were compared with those not using HT. Breast cancer tumor data were obtained from the Victorian Cancer Registry. Regression analysis was used to determine the associations between HT use or not at the time of diagnosis and tumor histology (ductal vs lobular), stage (I vs II, III, IV), HR status (ER+ or PR+ or both vs ER- or PR-). Of 1,377 women included in the analysis, 226 (16%) were using HT at the time of diagnosis. Of HT users, 20.4% had lobular breast cancer, 50% were stage I, and 85.8% had HR-positive tumors. Of non-users, 13.6% had lobular breast cancer, 48.2% were stage I, and 82.4% had HR-positive tumors. Use of systemic HT was associated with increased odds of having lobular compared with ductal breast cancer (OR = 1.75, 95% CI = 1.14-2.69, p = 0.01). There were no associations between HT use and either breast cancer stage or HR status. Women using systemic HT at the time of diagnosis were more likely to have lobular rather than ductal breast cancer compared with women not on HT.
Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal/pathology , Carcinoma, Lobular/pathology , Hormone Replacement Therapy/adverse effects , Adult , Aged , Female , Humans , Middle Aged , Neoplasm StagingABSTRACT
OBJECTIVE: The aim of this study was to evaluate the safety of 52 weeks of DHEA 50mg daily oral dose given to postmenopausal women with low libido to improve sexual function. METHOD: 93 postmenopausal women were enrolled in a 52-week randomised, double-blind, placebo-controlled trial and received either DHEA 50mg or placebo (PL) daily. The effects of DHEA versus placebo on lipid profile, insulin-glucose homeostasis and the endomentrium were assessed over 52 weeks. RESULTS: Oral DHEA, 50mg/day, was not associated with any effects on blood lipids or insulin resistance. The pattern of breakthrough bleeding did not substantially differ between the DHEA and PL groups and no significant adverse endometrial effects were apparent. CONCLUSIONS: The use of 50mg oral DHEA did not significantly alter lipid profile, insulin sensitivity or adversely affect the endometrium in postmenopausal women.
Subject(s)
Blood Glucose , Dehydroepiandrosterone/adverse effects , Endometrium/drug effects , Insulin/blood , Lipids/blood , Postmenopause , Sexual Dysfunctions, Psychological/drug therapy , Administration, Oral , Dehydroepiandrosterone/administration & dosage , Dehydroepiandrosterone/therapeutic use , Dose-Response Relationship, Drug , Double-Blind Method , Endometrium/diagnostic imaging , Female , Hormone Replacement Therapy/adverse effects , Humans , Insulin Resistance , Metrorrhagia , Middle Aged , Placebos/therapeutic use , UltrasonographyABSTRACT
OBJECTIVE: To report on the issues encountered in the recruitment of healthy naturally menopausal women in the community to a randomized placebo-controlled trial of dehydroepiandrosterone (DHEA) therapy for treatment of loss of sexual desire. METHODS: Recruitment of women was achieved by advertising and media publicity. We have reported on the method by which women initially contacted us and the reasons for nonparticipation. RESULTS: Nine hundred and eighteen women contacted us about participating in the study; 706 of these were telephoned screened, and 93 of these (10%) women were randomized to therapy. The main determinants for nonparticipation included ineligibility on phone screening (58%), withdrawal of interest either before or after screening (55%), and preexisting pathology after attending for screening (8%). CONCLUSIONS: Despite ongoing interest by women to participate in research for therapies to treat low libido, concerns about the use of any hormonal treatment and the time poverty experienced by many women at midlife present new barriers to recruitment and need to be considered in assessing the feasibility of studies in this field.
Subject(s)
Health Knowledge, Attitudes, Practice , Patient Selection , Postmenopause , Randomized Controlled Trials as Topic/methods , Women's Health , Aged , Australia , Dehydroepiandrosterone/therapeutic use , Double-Blind Method , Female , Humans , Libido , Middle Aged , Placebos , Sexual Dysfunction, Physiological/drug therapy , Socioeconomic FactorsABSTRACT
Buprenorphine was registered in Australia as a maintenance and detoxification agent for the management of opioid dependence in November, 2000, and became widely available in August, 2001. This paper provides an overview of key developments in the introduction of buprenorphine treatment in Australia, with an emphasis upon the delivery of services in community-based (primary care) settings. A central study in this work was the Buprenorphine Implementation Trial (BIT), a randomized, controlled trial comparing buprenorphine and methadone maintenance treatment delivered under naturalistic conditions by specialist and community-based service providers (general practitioners and community pharmacists) in 139 subjects across nineteen treatment sites. In addition to conventional patient outcome measures (treatment retention, drug use, psychosocial functioning, and cost effectiveness), the BIT study also involved the development and evaluation of clinical guidelines, training programs for clinicians, and client literature, which are described here. Integration of treatment systems (methadone with buprenorphine, specialist and primary-care programs) and factors thought to be important in the uptake of buprenorphine treatment in Australia since registration are discussed.