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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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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.
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Selective estrogen receptor modulators and phytoestrogens.
Oseni, T, Patel, R, Pyle, J, Jordan, VC
Planta medica. 2008;(13):1656-65
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Abstract
Scientific achievements in the last two decades have revolutionized the treatment and prevention of breast cancer. This is mainly because of targeted therapies and a better understanding of the relationship between estrogen, its receptor, and breast cancer. One of these discoveries is the use of synthetic selective estrogen modulators (SERMs) such as tamoxifen in the treatment strategy for estrogen receptor (ER)-positive breast cancer. Hundreds of thousands of lives have been saved because of this advance. Not only is tamoxifen used in the treatment strategy for patients who have breast cancer, but also for prevention in high-risk premenopausal women. Another synthetic SERM, raloxifene, which was initially used to prevent osteoporosis, is also as effective as tamoxifen for prevention in high-risk postmenopausal women. In certain regions of the world, particularly in Asia, a low incidence of breast cancer has been observed. These women have diets that are high in soy and low in fat, unlike the Western diet. Interest in the protective effects of soy derivatives has led to the research of phytoestrogens and metabolites of soy that are described by some as natural SERMs. As a result, many clinical questions have been raised as to whether phytoestrogens, which are also found in other natural foods, can protect against breast cancer. This article reviews the development and role of the more common SERMs, tamoxifen and raloxifene. In addition, this paper will also highlight the emerging studies on phytoestrogens and their similarity and dissimilarity to SERMs.
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[Glucocorticoid-induced osteoporosis].
Papierska, L, Rabijewski, M
Polskie Archiwum Medycyny Wewnetrznej. 2007;(8):363-9
Abstract
Long-term treatment with glucocorticoids can result in drug-related complications, among which osteoporosis is one of the most frequently encountered problems. Each patient treated with a dose of 7.5 mg or more of prednisone daily for at least 3 months can be affected. During the prolonged steroid use bone formation is inhibited while its resorption increases and negative calcium balance with secondary hyperparathyroidism occurs. In the affected bone, multiple focuses of osteomalacia and avascular necrosis are also described. The bone fracture risk is much higher than it can be suspected on the basis of bone mineral density (BMD) assessment. Therefore, in glucocorticoid-treated patients with only slightly decreased BMD (osteopenia according to the WHO criteria) treatment with antifracture agents should be initiated as soon as possible. Indication for therapy is a T-score of -1.5. Calcium supplementation with vitamin D represents an initial step of prevention and treatment. A first-line treatment effective in preventing bone fractures involves aminobisfosfonates such as alendronate and risedronate. Other effective agents are also estrogens, testosterone, selective estrogen receptor modulators and anabolic agents (parathormon, dehydroepiandrosteron, strontium ranelate).
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Cardiovascular actions of selective estrogen receptor modulators and phytoestrogens.
Nandur, R, Kumar, K, Villablanca, AC
Preventive cardiology. 2004;(2):73-9
Abstract
Cardiovascular disease is the leading cause of death among men and women in Western societies. Over the past decade, interest in a better understanding of gender differences in cardiovascular disease has heightened. Concomitantly, the use of hormone therapy for cardiovascular risk reduction in postmenopausal women has come into question in light of recent landmark clinical studies casting doubt on the benefits of this therapy. As a consequence, alternatives to conventional hormone replacement, including selective estrogen receptor modulators and phytoestrogens, have attracted considerable attention. The authors provide an up-to-date review of the clinical actions of selective estrogen receptor modulators on cardiovascular disease. The actions of tamoxifen, raloxifene, droloxifene, and soy phytoestrogens are discussed in the context of cardiovascular disease epidemiology, coronary events, clinical markers of cardiovascular risk, and vascular function. In addition, the authors' current understanding of the mechanism of action of these agents is discussed and recommendations for clinical practice are reviewed.
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Medical treatment of vertebral osteoporosis.
Lippuner, K
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2003;(Suppl 2):S132-41
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Abstract
Although osteoporosis is a systemic disease, vertebral fractures due to spinal bone loss are a frequent, sometimes early and often neglected complication of the disease, generally associated with considerable disability and pain. As osteoporotic vertebral fractures are an important predictor of future fracture risk, including at the hip, medical management is targeted at reducing fracture risk. A literature search for randomized, double-blind, prospective, controlled clinical studies addressing medical treatment possibilities of vertebral fractures in postmenopausal Caucasian women was performed on the leading medical databases. For each publication, the number of patients with at least one new vertebral fracture and the number of randomized patients by treatment arm was retrieved. The relative risk (RR) and the number needed to treat (NNT, i.e. the number of patients to be treated to avoid one radiological vertebral fracture over the duration of the study), together with the respective 95% confidence intervals (95%CI) were calculated for each study. Treatment of steroid-induced osteoporosis and treatment of osteoporosis in men were reviewed separately, based on the low number of publications available. Forty-five publications matched with the search criteria, allowing for analysis of 15 different substances tested regarding their anti-fracture efficacy at the vertebral level. Bisphosphonates, mainly alendronate and risedronate, were reported to have consistently reduced the risk of a vertebral fracture over up to 50 months of treatment in four (alendronate) and two (risedronate) publications. Raloxifene reduced vertebral fracture risk in one study over 36 months, which was confirmed by 48 months' follow-up data. Parathormone (PTH) showed a drastic reduction in vertebral fracture risk in early studies, while calcitonin may also be a treatment option to reduce fracture risk. For other substances published data are conflicting (calcitriol, fluoride) or insufficient to conclude about efficacy (calcium, clodronate, etidronate, hormone replacement therapy, pamidronate, strontium, tiludronate, vitamin D). The low NNTs for the leading substances (ranges: 15-64 for alendronate, 8-26 for risedronate, 23 for calcitonin and 28-31 for raloxifene) confirm that effective and efficient drug interventions for treatment and prevention of osteoporotic vertebral fractures are available. Bisphosphonates have demonstrated similar efficacy in treatment and prevention of steroid-induced and male osteoporosis as in postmenopausal osteoporosis. The selection of the appropriate drug for treatment of vertebral osteoporosis from among a bisphosphonate (alendronate or risedronate), PTH, calcitonin or raloxifene will mainly depend on the efficacy, tolerability and safety profile, together with the patient's willingness to comply with a long-term treatment. Although reduction of vertebral fracture risk is an important criterion for decision making, drugs with proven additional fracture risk reduction at all clinically relevant sites (especially at the hip) should be the preferred options.
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Selective estrogen receptor modulators in chronic renal failure.
Weisinger, JR, Heilberg, IP, Hernández, E, Carlini, R, Bellorin-Font, E
Kidney international. Supplement. 2003;(85):S62-5
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Abstract
BACKGROUND In addition to renal osteodystrophy, postmenopausal women on dialysis could be at risk of osteoporosis. Hormone replacement therapy (HRT) could have beneficial effects as well as potentially serious risks, especially in uremic women, due to the pharmacokinetics of estradiol in renal failure. Therapeutic alternatives, such as the selective estrogen receptor modulators (SERMs), have shown the benefits of estrogen on bone and serum lipid levels, without its adverse effects on the breast and endometrium, in nonuremic women. METHODS Recent data on the effect of the SERM raloxifene in bone and lipid metabolism in osteoporotic postmenopausal women on dialysis is reviewed. Since the estrogen receptor (ER) gene has been suggested as a candidate marker for osteoporosis, we investigated whether ER polymorphism could have predicted the BMD response to raloxifene. RESULTS Hemodialyzed women on raloxifene demonstrated increased trabecular bone mineral density (BMD) and decreased bone resorption markers. Similarly, LDL-cholesterol values dropped significantly. ER gene polymorphism analysis of baseline BMD parameters did not differ between PP/xx or Pp/Xx groups. Nevertheless, patients on raloxifene with PP/xx genotypes, but not those with Pp/Xx, showed a higher trabecular BMD after one year on treatment, suggesting that homozygous women for P or x alleles of the ER have a better BMD response to raloxifene. CONCLUSION Raloxifene and, most likely, other SERMs, could represent a good alternative to HRT in postmenopausal uremic women.
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Can calcium and vitamin D supplementation adequately treat most patients with osteoporosis?
Deal, C
Cleveland Clinic journal of medicine. 2000;(10):696-8
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Osteoporosis: which current treatments reduce fracture risk?
Baran, DT
Cleveland Clinic journal of medicine. 2000;(10):701-3
Abstract
Randomized controlled trials showed that several antiosteoporosis drugs decrease the incidence of fractures, which is a better measure of efficacy than are changes in bone mineral density or serum markers of bone turnover. With effective agents available, physicians should make osteoporosis treatment a priority, especially for patients at high risk, such as those who have already had a fracture.