The use of selective estrogen receptor modulators on bone health in men

Selective estrogen receptor modulators (SERMs) represent a class of drugs that act as agonist or antagonist for estrogen receptor in a tissue-specific manner. The SERMs drugs are initially used for the prevention and treatment of osteoporosis in postmenopausal women. Bone health in prostate cancer patients has become a significant concern, whereby patients undergo androgen deprivation therapy is often associated with deleterious effects on bone. Previous preclinical and epidemiological findings showed that estrogens play a dominant role in improving bone health as compared to testosterone in men. Therefore, this evidence-based review aims to assess the available evidence derived from animal and human studies on the effects of SERMs on the male skeletal system. The effects of SERMs on bone mineral density (BMD)/content (BMC), bone histomorphometry, bone turnover, bone strength and fracture risk have been summarized in this review.     

Calcium and vitamin D--for whom and when

The basis of 'nutritional' interventions for the prevention of postmenopausal osteoporosis and osteoporotic fracture is a large topic with much genetic and biochemical evidence, as well as the results of randomized controlled trials, to guide the investigator and clinician. The efficacy of treatment with calcium and vitamin D was once controversial, but with the advent of controlled clinical trials using bone mineral density as an endpoint it has become clear that calcium with or without vitamin D therapy can lead to reductions in the rate of bone loss in postmenopausal women of all ages. Furthermore, with certain caveats, calcium with vitamin D therapy in the older postmenopausal woman can lead to useful reductions in fracture rates and falls, especially in populations with reduced exposure to sunlight, which is potentially the majority of postmenopausal women in both developed and developing countries. However, estrogen, selective estrogen receptor modulators (SERMs) and bisphosphonates (especially when given in combination with calcium and vitamin D) are more efficacious in preventing fracture, particularly in postmenopausal patients with impaired bone structure.     

Tissue-selective agents: selective estrogen receptor modulators and the tissue-selective estrogen complex

Menopause has been associated with vasomotor symptoms, vulvar-vaginal atrophy and osteoporosis. One of the goals in exploring the potential of selective estrogen receptor modulators (SERMs) was to determine if they could prevent fractures, reduce menopausal symptoms and treat vaginal atrophy, while being neutral or protective on the uterus, breast and cardiovascular system. However, no SERM to date has achieved this goal. More recently, the idea of pairing a SERM with estrogen(s), known as a tissue-selective estrogen complex (TSEC), has been studied in postmenopausal women. A TSEC combines the complementary tissue-selective activities of a SERM and estrogen(s), in an attempt to gain the benefits of each with better overall tolerability. The Selective estrogen Menopause And Response to Therapy (SMART) trials were multicentre, randomized, double-blind, placebo- and active-controlled phase 3 studies evaluating the safety and efficacy of the SERM, bazedoxifene (BZA) paired with conjugated estrogens (CEs) in healthy postmenopausal women. In the first SMART trial, BZA/CE protected the endometrium from estrogenic stimulation, relieved hot flushes and maintained bone mass, with rates of amenorrhea, breast pain and overall adverse events similar to those with placebo in more than 3400 women over two years. BZA 20 mg was the lowest effective dose of BZA in BZA/CE to protect the endometrium and maintain bone mass when paired with CE 0.625 mg and CE 0.45 mg. In SMART-2, these BZA/CE doses significantly reduced the frequency and severity of hot flushes over 12 weeks. Collectively, these data support the TSEC containing BZA/CE as a new paradigm for treating menopausal symptoms and preventing osteoporosis while protecting the endometrium from unopposed estrogenic stimulation.     

Primary prevention of coronary heart disease in women

The British Menopause Society Council is committed to provide up-to-date authoritative reviews to aid health professionals to inform and advise women about key issues in postreproductive health. Coronary heart disease (CHD) is a leading cause of death in women. Observational studies have consistently shown estrogen to help prevent CHD in postmenopausal women. The large randomized controlled Women's Health Initiative (WHI) trial did not confirm these observational findings. However, further analyses of the WHI study as well as the observational Nurses' Health Study have now found that the timing of onset of hormone replacement therapy (HRT) use is important and that estrogen may have a protective role in CHD in women aged 50-59 years. This consensus statement will examine the evidence regarding HRT and non-estrogen therapies (lipid lowering agents, aspirin, antihypertensives, antidiabetic medications, selective estrogen receptor modulators [SERMs]) as well as diet, lifestyle and smoking cessation in the primary prevention of CHD in women.     

Testosterone and the breast

Although women have been treated with testosterone (T) for female sexual dysfunction since the 1950s, the role of T in normal female physiology is not yet fully defined. One of the major safety concerns of androgen therapy is whether androgens have a stimulatory effect on the breast that could lead to breast carcinomas. The proposed mechanisms for such stimulation include local estrogen production from the aromatase enzyme complex present in the breast tissue or by the direct stimulation of the androgen receptor. Predominant data from in vitro studies have shown that androgens actually have apoptotic and antiproliferative effects and not stimulatory effects. Animal models have shown similar results to in vitro studies, finding that androgens inhibit breast cancer growth. Prospective and retrospective epidemiological analyses have shown mixed outcomes, with no clear consensus regarding androgen use and breast cancer risk. Hyperandrogenism in patients with polycystic ovarian syndrome with elevated levels of endogenous T is not associated with an increased risk of breast cancer and may, in fact, be protective. Another human model with excess of T is female-to-male transgenderism, in which genotypic women are treated with large doses of exogenous T with no increased risk. High-dose androgen therapy also has been effective in treating patients with advanced breast cancer. Thus, the preponderance of data suggests that T use in females is not associated with an increased risk of breast carcinoma.     

Male breast cancer

Male breast cancer (MBC) is a rare disease. However, as global populace ages, there is a trend to MBC increasing. Although aetiology is still unclear, constitutional, environmental, hormonal (abnormalities in estrogen/androgen balance) and genetic (positive family history, Klinefelter syndrome, mutations in BRCA1 and specially BRCA2) risk factors are already known. Clinic manifestation is painless hard and fixed nodule in the subareolar region in 75% of cases, with nipple commitment earlier than in women. Breast cancer has similar prognostic factors in males and females, among which axillary adenopathy (present in 40–55% cases) is the most important one. Although mammography, ultrasonography and scintigraphy can be useful tools in diagnosis; clinical assessment, along with a confirmatory biopsy, remains the main step in the evaluation of men with breast lesions. Infiltrating ductal carcinoma is the most frequent histological type. The established standard of care is modified radical mastectomy followed by tamoxifen for endocrine-responsive positive disease, although other options are being explored. While similarities between breast cancer in males and females exist, it is not appropriate to extrapolate data from female disease to the treatment of male. There is a need for specific multi-institutional trials to better understanding of clinicopathologic features and establishment of optimal therapy for this disease.     

After Breast Cancer: Sexual Functioning of Sexual Minority Survivors

Research on sexual difficulties after cancer has neglected sexual minority women (SMW); for example, lesbian and bisexual women. Clinicians treating these women are therefore at a disadvantage as they lack information about sexual problems in this population. This study tested the hypothesis that SMW with breast cancer have poorer sexual function than SMW without breast cancer, distinguishing partnered from unpartnered women. Using convenience sample recruitment, we conducted a case-control study to compare survivors of breast cancers who are SMW, in other words, cases to controls, that is, SMW without cancer. Anonymous survey data were collected from 85 cases after they had completed active cancer treatment and 85 age- and partner-status matched controls with no history of any cancer. Participants' self-reported sexual frequency and sexual function measured by the Female Sexual Function Index were evaluated. Cases and controls did not differ in risk of sexual dysfunction or the level of overall sexual functioning; however, cases had lower sexual frequency and scored lower on desire and ability to reach orgasm, and higher on pain compared to controls. Results inform clinicians about sexual minority survivors' sexual domains affected by cancer. When discussing sexual problems and therapeutic options, sexual orientation should be ascertained.     

Management of premature menopause

There has been some confusion among women and health professionals since the publication of the Women's Health Initiative and Million Women studies about the management of premature ovarian failure (POF). Both studies were undertaken in women aged 50 and over, and cannot be extrapolated to their younger counterparts, who would normally be producing their endogenous estrogen, since they have functioning ovaries. Estrogen-based replacement therapy is the main stay of treatment for women with POF and is recommended at least until the average age of natural menopause (52 years in the UK). This view is endorsed by regulatory bodies such as the Committee on Safety of Medicines (now the Commission on Human Medicines) in the UK. No evidence shows that estrogen replacement increases the risk of breast cancer to a level greater than that found in normally menstruating women, and women with POF do not need to start mammographic screening early unless other risk factors are present, such as family history.     

l-Arginine and tetrahydrobiopterin,but not sodium nitrite partially restored erectile dysfunction in aged rats

This paper gives an overview of our own studies and the literature on the biosynthesis and metabolism of estrogens in elderly men, the estrogen action in the male, and the clinical usefulness of estrogen therapy, including the phytoestrogens. Finally, the paper includes a short review of our knowledge of xenoestrogens and men's sexual health. A strong estrogen-deficient status is seen in male patients with mutations of the estrogen receptors or in cases of deviations of the aromatase gene. On the other hand, there are no clear age-dependent changes in estrogen secretion. But, in men with disorders of glucose metabolism and also of increased body mass index, the serum estrogen concentrations are significantly elevated. There are also strong positive correlations between serum estrogen levels and bone density, including prevalence of fractures and mood in men. New fields of interest are natural fatty esters of endogenous estrogens, e.g. lipoprotein-associated estrogens, and the role and clinical significance of tissue-specific, local estrogen biosynthesis (e.g. different promoters of the aromatase gene). Exogenous estrogen treatment is focused today on patients with normal testosterone and low levels of circulating estrogens documented on several occasions and with clinical symptoms of hormone deficiency; male-to-female transsexuals; and selected patients with prostate cancer. Some clinical studies show the benefits of estrogen treatment on some cardiovascular parameters and for treating selected signs of mental stress. An indirect estrogen replacement can occur if dehydroepiandrosterone is given orally to men. The clinical usefulness of dissociated estrogens, including non-feminizing estrogens and selective estrogen receptor modulators, is still an open question. The beneficial action of phytoestrogens in lowering the clinical symptoms of benign prostatic hyperplasia is well documented. Finally, the question about the definitive influence of so-called endocrine disruptors (xenoestrogens) on sexual functions in men is also discussed.     

Bazedoxifene: a new selective estrogen receptor modulator for postmenopausal osteoporosis

An ongoing need for safe and effective pharmacological therapies exists for postmenopausal osteoporosis, which imposes a significant burden on both women and the health-care system. Bazedoxifene is a novel selective estrogen receptor modulator with a unique tissue-selectivity profile. In phase 3 clinical trials of nearly 10,000 postmenopausal women, bazedoxifene was shown to significantly reduce the risk of new vertebral fracture versus placebo, with favourable effects on bone mineral density, bone turnover markers and the lipid profile. Moreover, in a subgroup of women at increased risk of fracture, bazedoxifene significantly decreased non-vertebral fracture risk versus both placebo and raloxifene. Bazedoxifene has been shown to be safe and well tolerated, with no evidence of endometrial or breast stimulation. These data suggest that bazedoxifene may offer significant clinical benefit for postmenopausal women with or at risk of developing osteoporosis, which may subsequently lessen the medical and economic burden of this disease.     

COMMUNITY AND THE PUBLIC BODY IN BREAST CANCER MEDIA ACTIVISM

In this article, I consider how communities form around health care advocacy and activism. My concern is the place of visual media in the politics of breast cancer. Art photography and film are considered against mainstream images and media campaigns focusing on breast cancer. The primary work considered is the self-portrait photography of the artist Matuschka and the film The Body Beautiful by Ngozi Onwurah. I argue that these alternative texts help us to think about the ways in which issues such as race, age and beauty are key aspects in the experience of breast cancer, and not tangential cultural issues or ‘appearance-related side effects’, as one breast cancer support programme puts it.     

Cancer Knowledge and Examination Frequency in College Students

Abstract

College students are now being considered an appropriate target for cancer education programs. However, research has demonstrated that only a fraction of those individuals knowledgeable about the importance of cancer examinations actually practice these examinations. This study investigated whether the personality construct of repression-sensitization could identify which individuals would or would not practice regular examinations for breast, cervical, and testicular cancer. College students were identified as repressors, neutral, or sensitizers and tested as to their knowledge and examination frequency for breast, cervical, and testicular cancer. After a cancer lecture, this information was reasessed. No differences were found among repressors, neutrals, or sensitizers in cancer knowledge or examination frequency, either prelecture or postlecture. Cancer knowledge significantly increased after the lecture for both males and females. No change was found in the frequency of breast self-examination, while frequency of pap smears declined after the lecture. In contrast, testicular self-examination frequency increased. The implications of these results for future research are discussed.     

Active aging—spunky survivorship? Discourses and experiences of the years beyond breast cancer

Recent critical gerontology has drawn attention to the origins, functions and consequences for elders of the ‘successful aging’ discourse. In this paper we describe parallels between successful aging and what we are calling ‘spunky survivorship,’ the contemporary subject position made available to women in the years after a breast cancer diagnosis. The central focus of the paper is a study about the intersections between a dominant discourse of breast cancer survivorship, and the perceptions and experiences of women living the years beyond breast cancer. It is our hope that the analysis presented here will suggest new pathways for exploring the relationship between discourses of successful aging and people's ideas and feelings about growing older.     

Utility of linking survey and registry data to evaluate interventions and policies to address disparities in breast cancer survivorship among young women

PurposeThere is limited research linking data sources to evaluate the multifactorial impacts on the quality of treatment received and financial burden among young women with breast cancer. To address this gap and support future evaluation efforts, we examined the utility of combining patient survey and cancer registry data.Patient and MethodsWe administered a survey to women, aged 18–39 years, with breast cancer from four U.S. states. We conducted a systematic response-rate analysis and evaluated differences between racial groups. Survey responses were linked with cancer registry data to assess whether surveys could reliably supplement registry data.ResultsA total of 830 women completed the survey for a response rate of 28.4 %. Blacks and Asian/Pacific Islanders were half as likely to respond as white women. Concordance between survey and registry data was high for demographic variables (Cohen’s kappa [k]: 0.879 to 0.949), moderate to high for treatments received (k: 0.467 to 0.854), and low for hormone receptor status (k: 0.167 to 0.553). Survey items related to insurance status, employment, and symptoms revealed racial differences.ConclusionCancer registry data, supplemented by patient surveys, can provide a broader understanding of the quality of care and financial impacts of breast cancer among young women.     

Mutually Dependent Health Beliefs Associated With Breast Self-examination in British Female University Students

Abstract

Objective: Whereas research suggests young women's beliefs about breast cancer (susceptibility/severity) and its early detection (barriers/benefits) reliably distinguish breast self-examiners from nonexaminers, this study assessed whether these impressions are interreliant, especially in the context of familial risk. Participants: The sample comprised over 200 female undergraduates from a university in England, United Kingdom. Methods: Participants completed a self-administered survey on their attitudes concerning breast cancer and early detection. Data were analyzed using logistic regression analysis. Results: Nonexaminers were distinguished by a combination of greater perceived hindrances to self-examinations and stronger appraisals of breast cancer severity, and also by a permutation of fewer perceived benefits in self-examinations and lower perceived susceptibility to breast cancer. The latter interaction persisted after accounting for family history. Conclusions: Interwoven attitudes may depict sophisticated efforts on the part of nonexaminers to justify inaction. Clinical implications for college health providers are considered.     

Motivational Factors Affecting Patient Attrition in a Weight Reduction Program

Abstract

The study hypothesizes that the greater the satisfaction of a patient's basic motivational needs, the greater the likelihood that the patient will complete the program. Patients were given a self-report questionnaire to assess the strength of their basic motivational needs as they entered the program; and a Likert-type questionnaire concerning satisfaction of needs as they left the program. The results show that those who completed the program experienced greater satisfaction of needs than those who did not complete the program. Analysis of covariance of completion of the program and need satisfaction was significant (p < .01) thus supporting the hypothesis.

“Long-term Oral Contraceptive Use and the Risk of Breast Cancer,” THE CENTERS FOR DISEASE CONTROL CANCER AND STEROID HORMONE STUDY. Using oral contraceptives for long periods or using them when one has other risk factors has been hypothesized to increase the risk of breast cancer. To study these issues, we analyzed data from a multicenter, case-control investigation—the Centers for Disease Control's Cancer and Steroid Hormone Study. All women 20 to 54 years old with a first diagnosis of breast cancer ascertained by eight population-based cancer registries are study subjects; controls are selected at random from the general population of these eight areas. Analysis of the first 689 cases and 1,077 controls studied showed that women who had used oral contraceptives at some time in their lives had a relative risk of 0.9 compared with never-users (95% confidence interval, 0.8 to 1.2). Neither duration of oral contraceptive use nor time since first use altered a user's risk of breast cancer; women whose first use was more than 15 years ago and who used oral contraceptives for 11 years or more had a relative risk of 0.8 (0.5 to 1.4). Oral contraceptive use did not increase the risk of breast cancer among women with benign breast disease or a family history of breast cancer. Oral contraceptive use before a woman's first pregnancy did not increase her risk of breast cancer significantly more than other methods of delaying first pregnancy. This study provides no support to the hypothesis that oral contraceptive use increases a woman's risk of breast cancer. (Journal of the American Medical Association 1983;249:1591–1595.)

“Oral Contraceptive Use and the Risk of Ovarian Cancer,” THE CENTERS FOR DISEASE CONTROL CANCER AND STEROID HORMONE STUDY. Since oral contraceptives have been used by more than 40 million American women, an association between oral contraceptives and ovarian cancer could have a substantial public health impact. The Centers for Disease Control, Atlanta, is studying this relationship as part of a multicenter, case-control study—the Cancer and Steroid Hormone Study. During the first ten months of the study, we enrolled 179 women aged 20 to 54 years who had been ascertained to have newly diagnosed ovarian cancer by eight population-based cancer registries. From the general population of those eight areas, we selected as controls 1,642 women with intact ovaries. Users of oral contraceptives had an age-adjusted risk of ovarian cancer developing of 0.6 relative to those who had never used them (95% confidence interval, 0.4 to 0.9). The risk of ovarian cancer decreased with increasing duration of oral contraceptive use and remained low long after cessation of use. These results were not accounted for by parity, infertility, or other potentially confounding factors. We estimate that more than 1,700 cases of ovarian cancer are averted each year by past and current oral contraceptive use among women in the United States. (Journal of the American Medical Association 1983;249:1596–1599.)     

Men's psychological functioning in the context of women's breast cancer

Previous research indicates that men are affected when their female partners have breast cancer. However, little is known about what predicts men's psychological well-being in this context. The current investigation involved couples in which the woman had early stage breast cancer and explored the degree to which men's positive and negative well-being was related to women's well-being, women's physical symptoms, relationship functioning, and relationship duration. The findings indicate that all of these factors play a role and interact in predicting men's well-being. In particular, when women have a high level of physical symptoms, the typical associations between men's well-being with women's well-being and relationship adjustment no longer persist. Implications for working with couples addressing health problems are provided.     

Breast cancer coverage in China and the United States: a comparative analysis of wire service news stories

The incidence rate of breast cancer is relatively high but declining in the United States whereas it is relatively low but increasing in China. This study analyzes coverage from the Associated Press (AP) and the Xinhua News Agency (Xinhua) to compare how news media in each nation have covered breast cancer. The results indicate that the AP was more likely to cover treatment and personal stories whereas Xinhua was more likely to cover risk reduction and prevention and to cover early detection and diagnosis. Subtler differences also emerged in coverage of breast cancer. The patterns observed may reflect not only differences between the two nations in incidence rates and efforts to address the disease but also broader differences in their news and medical values, practices, and institutions. News coverage of breast cancer, in turn, may influence how citizens of each nation will form perceptions regarding the disease.     

U.S. Latinas' Knowledge and Attitudes toward Mammography: Meta-synthesis

Breast cancer is the leading cause of cancer death among Latinas in the United States. The primary purpose of this meta-synthesis was to integrate findings on qualitative studies related to Latinas' knowledge, attitudes, and perceptions regarding breast cancer and its prevention through mammography. After applying inclusion criteria, eleven studies were located. Results were organized around four areas of inquiry that cross-cut primary studies: 1) Latina participants' knowledge of breast cancer and its prevention; 2) barriers for regular mammography; 3) facilitators that encouraged such screening; and 4) recommendations on how to provide screening for Latina women.     

Improving quality of life after breast cancer: prevention of other diseases

Many women with breast cancer will be diagnosed at an early stage through screening programmes. Furthermore, most women affected by breast cancer will not die from it but from other diseases, owing to recent improvements in treatment. This article assesses whether breast cancer survivors suffer more frequently from other diseases. Specifically, it examines whether they have a higher incidence of other cancers, cardiovascular events and osteoporotic fractures. Women with breast cancer and three or more co-morbid conditions have a 20-fold higher rate of mortality from causes other than breast cancer and a 4-fold higher rate of all-cause mortality when compared with patients who have none. Breast cancer survivors are at increased risk of other cancers, such as stomach, colorectal and lung. Radiotherapy, trastuzumab and aromatase inhibitors increase the risk of cardiovascular disease. However, tamoxifen does not, although it is associated with an increased risk of venous thromboembolism. Aromatase inhibitors, but not tamoxifen, increase the risk of osteoporotoic fracture and bisphosphonate therapy should be considered.