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Alternatives to Testosterone Therapy: A Review.
Lo, EM, Rodriguez, KM, Pastuszak, AW, Khera, M
Sexual medicine reviews. 2018;(1):106-113
Abstract
INTRODUCTION Although testosterone therapy (TTh) is an effective treatment for hypogonadism, recent concerns regarding its safety have been raised. In 2015, the US Food and Drug Administration issued a warning about potential cardiovascular risks resulting from TTh. Fertility preservation is another reason to search for viable alternative therapies to conventional TTh, and in this review we evaluate the literature examining these alternatives. AIMS To review the role and limitations of non-testosterone treatments for hypogonadism. METHODS A literature search was conducted using PubMed to identify relevant studies examining medical and non-medical alternatives to TTh. Search terms included hypogonadism, testosterone replacement therapy, testosterone therapy, testosterone replacement alternatives, diet and exercise and testosterone, varicocele repair and testosterone, stress reduction and testosterone, and sleep apnea and testosterone. MAIN OUTCOME MEASURES Review of peer-reviewed literature. RESULTS Medical therapies examined include human chorionic gonadotropins, aromatase inhibitors, and selective estrogen receptor modulators. Non-drug therapies that are reviewed include lifestyle modifications including diet and exercise, improvements in sleep, decreasing stress, and varicocele repair. The high prevalence of obesity and metabolic syndrome in the United States suggests that disease modification could represent a viable treatment approach for affected men with hypogonadism. CONCLUSIONS These alternatives to TTh can increase testosterone levels and should be considered before TTh. Lo EM, Rodriguez KM, Pastuszak AW, Khera M. Alternatives to Testosterone Therapy: A Review. Sex Med Rev 2018;6:106-113.
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Current medical management of endocrine-related male infertility.
Ring, JD, Lwin, AA, Köhler, TS
Asian journal of andrology. 2016;(3):357-63
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Abstract
Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can be contributory especially if the sample returns normal. Male infertility can be due to identifiable hormonal or anatomical etiologies that may be reversible or irreversible. This manuscript will highlight existing guidelines and our recommendations for hormone evaluation for male infertility and empiric therapies including multivitamins, estrogen receptor modulators (clomiphene), estrogen conversion blockers (anastrozole), and hormone replacement.
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Ovulation induction in polycystic ovary syndrome: Current options.
Legro, RS
Best practice & research. Clinical obstetrics & gynaecology. 2016;:152-159
Abstract
There are a variety of effective treatment options to induce ovulation in women with polycystic ovary syndrome (PCOS). The most effective treatments are primarily reproductive and target the hypothalamic-pituitary-ovarian (HPO) axis. Letrozole, an aromatase inhibitor, is headed toward replacing clomiphene, a selective estrogen receptor modulator, as the first-choice option. Metabolic treatments likely work indirectly through the HPO axis. Many metabolic treatments have shown initial promise and later failed (troglitozone or d-chiro-inositol) or disappointed (metformin); further studies are needed of newer agents to treat type 2 diabetes. Weight loss interventions, lifestyle related, through obesity drugs or through bariatric surgery have shown mixed results on pregnancy outcomes. With both reproductive and metabolic treatments, combination therapies (such as metformin and clomiphene together) may offer greater benefit to distinct subgroups of patients.
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Pause menopause with Rhodiola rosea, a natural selective estrogen receptor modulator.
Gerbarg, PL, Brown, RP
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2016;(7):763-9
Abstract
BACKGROUND Menopausal women are challenged by the adverse effects of estrogen loss on energy, mood, cognitive function, and memory. These stresses are compounded by increased risks for cardiovascular disease, osteoporosis, and cancer. Known to have neuroprotective, cardio-protective, anti-oxidative and anti-carcinogenic effects, Rhodiola rosea extracts have also been shown to improve energy, mood, cognitive function and memory. PURPOSE We propose that R. rosea be investigated for use as a potential selective estrogen receptor modulator (SERM) in the prevention and treatment of menopause-related fatigue, stress, depression, cognitive decline, memory impairment, cardiovascular disease, osteoporosis and cancer. METHOD This paper briefly reviews the relationship between estrogen decline and menopause-related health risks, the molecular mechanisms underlying estrogenic effects on health, and the evidence indicating beneficial effects of R. rosea extracts on these mechanisms and health risks. Mechanisms include non-genomic and genomic effects, for example: activation of intra-cellular signal transduction pathways by binding to estrogen receptors, ERα-mediated activation of endothelial nitric oxide synthase with increased nitric oxide release; and anti-inflammatory effects, counteracting TNFα by inhibiting nuclear factor-Kappa-B (NF-KB) and protection of osteoblasts from hydrogen peroxide. A clinical case illustrating treatment of a menopausal woman with R. rosea is presented. Risks, benefits, gaps in knowledge, and future directions are discussed. CONCLUSION Numerous lines of evidence indicate that R. rosea should be investigated as a potential selective estrogen receptor modulator (SERM) to prevent, delay or mitigate menopause-related cognitive, psychological, cardiovascular and osteoporotic conditions.
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[Current advances and issues in selective estrogen receptor modulator (SERM) treatment].
Ohta, H
Clinical calcium. 2014;(1):45-52
Abstract
The use of selective estrogen receptor modulators (SERMs) was limited at first to relatively young women and was overestimated for the risk of venous thromboembolism (VTE) due to their estrogen-like effects. Ten years of clinical experience with the SERMs in Japan suggest that they can be used without concern for VTE and are efficacious in older women. Thus, the SERMs are now being recognized as agents readily available for clinical use. Furthermore, unlike the bisphosphonates, their physiological hormone-like effects have led to their widespread use in clinical settings. Future issues in treatment with the SERMs include generation of evidence for their efficacy in improving bone quality as well as for their efficacy in the oldest population. Given their excellent, well-balanced efficacy and safety profile as well as their convenience, however, the SERMs are thought likely to become further established as the standard of care in osteoporosis and other diseases.
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Musculoskeletal ageing and primary prevention.
Nedergaard, A, Henriksen, K, Karsdal, MA, Christiansen, C
Best practice & research. Clinical obstetrics & gynaecology. 2013;(5):673-88
Abstract
Loss of musculoskeletal mass and function is a natural ageing trait, reinforced by an unhealthy life style. Loss of bone (osteoporosis) and muscle (sarcopaenia) are conditions whose prevalence are increasing because of the change in population distribution in the western world towards an older mean age. Improvements in lifestyle factors, such as diet, smoking and exercise, are the most powerful tools to combat this decline efficiently; however, public health interventions aimed at tackling these problems have shown abysmal success at the population level, mostly due to failure in compliance. With these issues in mind, we believe that the primary prevention modality in coming decades will be pharmacological. We review the basic biology of musculoskeletal ageing and what measures can be taken to prevent ageing-associated loss of musculoskeletal mass and function, with particular emphasis on pharmacological means.
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Prenylated isoflavonoids from plants as selective estrogen receptor modulators (phytoSERMs).
Simons, R, Gruppen, H, Bovee, TF, Verbruggen, MA, Vincken, JP
Food & function. 2012;(8):810-27
Abstract
Isoflavonoids are a class of secondary metabolites, which comprise amongst others the subclasses of isoflavones, isoflavans, pterocarpans and coumestans. Isoflavonoids are abundant in Leguminosae, and many of them can bind to the human estrogen receptor (hER) with affinities similar to or lower than that of estradiol. Dietary intake of these so-called phytoestrogens has been associated with positive effects on menopausal complaints, hormone-related cancers, and osteoporosis. Therefore, phytoestrogens are used as nutraceuticals in functional foods or food supplements. Most of the isoflavonoids show agonistic activity towards both hERα and hERβ, the extent of which is modulated by the substitution pattern of their skeleton (i.e.-OH, -OCH(3)). Interestingly, substitutions consisting of a five-carbon prenyl group often seem to result in an antiestrogenic activity. There is growing evidence that the action of some of these prenylated isoflavonoids is tissue-specific, suggesting that they act like selective estrogen receptor modulators (SERMs), such as the well-known chemically synthesized raloxifene and tamoxifen. These so-called phytoSERMS might have high potential for realizing new food and pharma applications. In this review, the structural features of isoflavonoids (i.e. the kind of skeleton and prenylation (e.g. chain or pyran), position of the prenyl group on the skeleton, and the extent of prenylation (single, double)) are discussed in relation to their estrogenic activity. Anti-estrogenic and SERM activity of isoflavonoids was always associated with prenylation, but these activities did not seem to be confined to one particular kind/position of prenylation or isoflavonoid subclass. Few estrogens with agonistic activity were prenylated, but these were not tested for antagonistic activity; possibly, these molecules will turn out to be phytoSERMs as well. Furthermore, the data on the dietary occurrence, bioavailability and metabolism of prenylated isoflavonoids are discussed.
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Future directions in cancer prevention.
Umar, A, Dunn, BK, Greenwald, P
Nature reviews. Cancer. 2012;(12):835-48
Abstract
Prevention of cancer remains the most promising strategy for reducing both its incidence and the mortality due to this disease. For more than four decades, findings from epidemiology, basic research and clinical trials have informed the development of lifestyle and medical approaches to cancer prevention. These include selective oestrogen receptor modulators and aromatase inhibitors for breast cancer, the 5-α-reductase inhibitors finasteride and dutasteride for prostate cancer, and the development of vaccines for viruses that are associated with specific cancers. Future directions include genetic, proteomic and other molecular approaches for identifying pathways that are associated with cancer initiation and development, as well as refining the search for immunologically modifiable causes of cancer.
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Current options for the management of postmenopausal osteoporosis.
Lecart, MP, Reginster, JY
Expert opinion on pharmacotherapy. 2011;(16):2533-52
Abstract
INTRODUCTION Osteoporosis is a well-recognized disease with severe consequences if left untreated. The prevention of osteoporosis-associated fractures should include fall prevention, calcium supplementation and life-style advice, as well as pharmacological therapy using agents with proven antifracture efficacy. AREAS COVERED This manuscript offers an evidence-based critical assessment of the currently available efficacy data on all new chemical entities that have been granted a marketing authorization for the management of primary osteoporosis in women. EXPERT OPINION The availability of new therapeutic agents makes clinical decision making in osteoporosis more complex. Therapeutic decisions should be based on a balance between the benefits and risks of treatment, which must be carefully considered in each particular case, both by the physician and the patient. Indeed, no single agent is appropriate for all patients. Therefore, treatment decisions should be made on a tailor-made basis, taking into account all measures of treatment effect and risk, before making informed judgments about the best individual treatment option.
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Breast cancer medications and vision: effects of treatments for early-stage disease.
Eisner, A, Luoh, SW
Current eye research. 2011;(10):867-85
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Abstract
This review concerns the effects on vision and the eye of medications prescribed at three phases of treatment for women with early-stage breast cancer (BC): (1) adjuvant cytotoxic chemotherapy, (2) adjuvant endocrine therapy, and (3) symptomatic relief. The most common side effects of cytotoxic chemotherapy are epiphora and ocular surface irritation, which can be caused by any of several different regimens. Most notably, the taxane docetaxel can lead to epiphora by inducing canalicular stenosis. The selective-estrogen-receptor-modulator (SERM) tamoxifen, long the gold-standard adjuvant-endocrine-therapy for women with hormone-receptor-positive BC, increases the risk of posterior subcapsular cataract. Tamoxifen also affects the optic nerve head more often than previously thought, apparently by causing subclinical swelling within the first 2 years of use for women older than ~50 years. Tamoxifen retinopathy is rare, but it can cause foveal cystoid spaces that are revealed with spectral-domain optical coherence tomography (OCT) and that may increase the risk for macular holes. Tamoxifen often alters the perceived color of flashed lights detected via short-wavelength-sensitive (SWS) cone response isolated psychophysically; these altered perceptions may reflect a neural-response sluggishness that becomes evident at ~2 years of use. The aromatase inhibitor (AI) anastrozole affects perception similarly, but in an age-dependent manner suggesting that the change of estrogen activity towards lower levels is more important than the low estrogen activity itself. Based on analysis of OCT retinal thickness data, it is likely that anastrozole increases the tractional force between the vitreous and retina. Consequently, AI users, myopic AI users particularly, might be at increased risk for traction-related vision loss. Because bisphosphonates are sometimes prescribed to redress AI-induced bone loss, clinicians should be aware of their potential to cause scleritis and uveitis occasionally. We conclude by suggesting some avenues for future research into the visual and ocular effects of AIs, particularly as relates to assessment of cognitive function.