Use Of Hormonal Agents Research Articles

Histomorphology of the ovaries of rabbits does during ovulation induced by the combined use of gonadotropins

Hormonal stimulation of folliculogenesis is a general method of increasing reproductive capacity in rabbits; however, studying the safety of the developed protocols remains an urgent scientific task. The use of hormonal agents is due to the physiological characteristics of rabbits, primarily coitus-dependent mechanisms of ovulation. Applying gonadotropin-releasing analogs depends on mature follicles ready for ovulation in the ovary. It, therefore, has limited effectiveness for rabbits of the “zero” cycle that have not yet given birth. Therefore, such females are recommended to use medications based on gonadotropins obtained from the serum of foal mares (eCG) or human chorionic gonadotropin (hCG). There is limited data on the combined use of gonadotropins, especially the long-term administration in different doses. Thus, the research aimed to conduct a morphological evaluation of rabbit's ovaries with combined serum and chorionic gonadotropins to stimulate folliculogenesis before artificial insemination to assess the safety of the proposed dosages and long-term administration. Stimulation of ovulation in rabbits of experimental groups was caused by the combined use of serum and chorionic gonadotropins (eCG – 400 IU; hCG – 200 IU) for experimental groups 1 and 2 at a dose of 40 IU and 24 IU, respectively. Females of the control group were induced to ovulate by subcutaneous injection of 0.2 ml of gonadotropin-releasing hormone analog. Ovaries were collected on the seventh day of gestation after the euthanasia of the rabbit with prior premedication. After dissection and macroscopic examination, the ovaries were fixed in a 10% aqueous solution of neutral formalin. Histological slides were made according to the general method by pouring in paraffin and subsequent staining with hematoxylin and eosin. The research has established that repeated (during five reproductive cycles) combined use of serum and chorionic gonadotropins has dose-dependent effectiveness and can cause dysfunction of ovaries and blood circulation. Pathological changes may acquire a systemic character with the manifestation of critical conditions for the health and life of rabbits. The stimulating effect of the combined use of eCG and hCG was detected at a dose of 40 IU, and the inhibition of folliculogenesis was observed at 24 IU. Since the premises for the hyperandrogenism were found microscopically, it was essential to investigate the level of androgens in the blood of rabbits after using a dose of 24 IU. At the same time, both doses of gonadotropins affect the reactivity of the endothelium, which is manifested by the presence of intravascular vesicles and changes in the rheological properties of blood.

MP67-14 VARIATION OF HORMONAL AGENT USAGE WITH POSTOPERATIVE RADIATION THERAPY: RESULTS FROM A POPULATION BASED COHORT OF PROSTATE CANCER PATIENTS IN COMMUNITY ONCOLOGY PRACTICES

You have accessJournal of UrologyCME1 Apr 2023MP67-14 VARIATION OF HORMONAL AGENT USAGE WITH POSTOPERATIVE RADIATION THERAPY: RESULTS FROM A POPULATION BASED COHORT OF PROSTATE CANCER PATIENTS IN COMMUNITY ONCOLOGY PRACTICES Rodrigo R Pessoa, Tyler Robin, Thomas Flaig, Elizabeth Molina, Boris Gershman, Eric Ballon-Landa, Corbin Eule, Elizabeth Kessler, Brian Chapin, Marc C Smaldone, and Simon P Kim Rodrigo R PessoaRodrigo R Pessoa More articles by this author , Tyler RobinTyler Robin More articles by this author , Thomas FlaigThomas Flaig More articles by this author , Elizabeth MolinaElizabeth Molina More articles by this author , Boris GershmanBoris Gershman More articles by this author , Eric Ballon-LandaEric Ballon-Landa More articles by this author , Corbin EuleCorbin Eule More articles by this author , Elizabeth KesslerElizabeth Kessler More articles by this author , Brian ChapinBrian Chapin More articles by this author , Marc C SmaldoneMarc C Smaldone More articles by this author , and Simon P KimSimon P Kim More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003330.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The optimal hormonal agent for postoperative radiation therapy remains to be defined with either LH-RH agents or androgen receptor blockers. Androgen deprivation therapy appears to be important for some patients receiving postoperative radiation therapy but there are differences in side effects and quality of life. Thus, we used a large national database of community practices to identify practice patterns with hormonal agents in the postoperative radiation therapy settings. METHODS: From the CancerLinQ database, which represents more than a 100 community oncology practices in the U.S., we included all men who underwent radical prostatectomy and then received adjuvant or salvage radiation therapy from 2000 to 2021. The primary outcome was concomitant use of hormonal therapy including luteinizing hormone – releasing hormone (LH-RH) agents or androgen receptor blockers. Multivariable logistic regression analyses were used to elucidate patient characteristics associated with use of each class of hormonal agents. RESULTS: Among the 390 surgically treated patients receiving postoperative radiation therapy, 50.7%(n=198) received no hormonal agents, 23.6 % (n=92) received LH-RH agents, and 22.82% (n=89) received both LH-RH agents and androgen receptor blocker. Only 2.8% (n=11) received androgen receptor blocker alone. Among patients with salvage radiation therapy at PSA>0.7 ng/dl, 51.6% did not receive any form of hormonal therapy. On multivariable analysis, patients with pN1+ compared with pN0 had higher odds of receiving LH-RH agents (OR: 3.21; p=0.01) during postoperative radiation therapy. Conversely, African American men were less likely to receive androgen receptor blockers compared to white men (OR: 0.24; p=0.004). Use of hormonal agents were not associated with postoperative radiation therapy intent. CONCLUSIONS: Among patients treated in community-based oncology practices in the U.S., most are not receiving any form of hormonal agents with postoperative radiation therapy. Racial disparities also exist in the use of androgen receptor blockers during post-prostatectomy radiation therapy. Increased attention is needed to disseminate evidence into clinical practice. Source of Funding: Schramm Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e948 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rodrigo R Pessoa More articles by this author Tyler Robin More articles by this author Thomas Flaig More articles by this author Elizabeth Molina More articles by this author Boris Gershman More articles by this author Eric Ballon-Landa More articles by this author Corbin Eule More articles by this author Elizabeth Kessler More articles by this author Brian Chapin More articles by this author Marc C Smaldone More articles by this author Simon P Kim More articles by this author Expand All Advertisement PDF downloadLoading ...

Exploring new pathways in endocrine-resistant breast cancer.

The most common breast cancer (BC) subtypes are hormone-dependent, being either estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), or both, and altogether comprise the luminal subtype. The mainstay of treatment for luminal BC is endocrine therapy (ET), which includes several agents that act either directly targeting ER action or suppressing estrogen production. Over the years, ET has proven efficacy in reducing mortality and improving clinical outcomes in metastatic and nonmetastatic BC. However, the development of ET resistance promotes cancer survival and progression and hinders the use of endocrine agents. Several mechanisms implicated in endocrine resistance have now been extensively studied. Based on the current clinical and pre-clinical data, the present article briefly reviews the well-established pathways of ET resistance and continues by focusing on the three most recently uncovered pathways, which may mediate resistance to ET, namely receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK), nuclear factor kappa B (NFκB), and Notch. It additionally overviews the evidence underlying the approval of combined therapies to overcome ET resistance in BC, while highlighting the relevance of future studies focusing on putative mediators of ET resistance to uncover new therapeutic options for the disease.

Prevalence of Dysmenorrhea among Female Adolescents in Dubai: A Cross-Sectional Study

Objective: This study aimed to investigate the prevalence of dysmenorrhea among adolescents in Dubai, and its effect on their academic and athletic performance. Methods: This was a cross-sectional study conducted in ten randomly selected private and government high schools in Dubai, United Arab Emirates. Using both the English and Arabic translated version of the Women’s Health Symptom Survey Questionnaire World, data was collected from 456 female students of grades 7 - 12, aged 11 - 19 years. Results: Dysmenorrhea was a crucial problem reported by 432 (94.7%) of the participants. Of the total number, 208 (45%) participants reported experiencing severe pain during menstruation and 152 (33.4%) students reported being absent from school during every menstrual cycle. Nonsteroidal anti-inflammatory drugs (NSAIDs) were used by 147 (32.3%) students, and majority reported no or little improvement. The percentage of students who experienced menstrual pain with micturition or defecation was 43.1% and 46.7%, respectively. None of the participants reported the use of hormonal agents. Conclusion: The unexpected high number of female adolescents who reported symptoms of primary dysmenorrhea necessitating treatment, as well as subsequent school absenteeism, calls for implementation of a screening questionnaire for early detection of persistent primary dysmenorrhea. Moving from surgical to clinical diagnosis of endometriosis can contribute greatly to improving the quality of life and reproductivity of female adolescents with severe dysmenorrhea.

Clinical Review on the Management of Hormone Receptor-Positive Metastatic Breast Cancer.

The natural history of hormone receptor-positive breast cancer tends to be more favorable than other subtypes such as human epidermal growth factor receptor 2-amplified and triple-negative. In addition, the natural dependence on steroid hormone signaling has allowed for therapeutic targeting of this pathway and significant improvements in survival while maintaining quality of life: the two main goals in management of the disease. The sequential use of endocrine agents including the selective estrogen receptor modulators (tamoxifen), aromatase inhibitors (letrozole, anastrozole, and exemestane) and the selective estrogen receptor degrader fulvestrant has been the backbone of management for years. In the past decade, the introduction of molecularly targeted agents against intracellular targets such as mammalian target of rapamycin (everolimus), cyclin-dependent kinases 4 and 6 (palbociclib, ribociclib, and abemaciclib), and phosphatidylinositol 3-kinase (alpelisib) has offered patients effective nonchemotherapy-based options, which are improving outcomes. Although knowledge gaps still exist in regard to the optimal sequencing of these new regimens, they have expanded our repertoire of options for patients and have shifted the need for cytotoxic chemotherapy and its associated complications to later lines. Still, formatting a plan for these patients includes taking into account traditional prognostic factors such as menopausal status, previous treatments, disease-free interval for those patients with early breast cancer that has recurred, and tumor burden. To assist in developing this treatment plan, we will review the current data with systemic agents in the management of these patients.

Bone Targeting Agents in Patients with Metastatic Prostate Cancer: State of the Art

Simple SummaryOver the disease course of metastatic prostate cancer, approximately the 90% of patients develops bone metastases, with bone involvement frequently leading to various skeletal complications including pathological fractures, spinal cord compression, and pain. Notably enough, the peculiar inclination of prostate cancer cells to seed the bone is considered an important cause of morbidity for prostate cancer patients. Recent years have witnessed the advent of several novel treatments for prostate cancer, and therapeutic paradigms are rapidly shifting. In this review, we aim at giving an overview of current knowledge on the relationship between prostate cancer and bone, especially focusing on the use of bone-targeted agents in this setting.Bone health represents a major issue in castration-resistant prostate cancer (CRPC) patients with bone metastases; in fact, the frequently prolonged use of hormonal agents causes important modifications in physiological bone turnover and most of these men will develop skeletal-related events (SREs), including spinal cord compression, pathologic fractures and need for surgery or radiation to bone, which are estimated to occur in almost half of this patient population. In the last decade, several novel therapeutic options have entered into clinical practice of bone metastatic CRPC, with recent approval of enzalutamide and abiraterone acetate, cabazitaxel chemotherapy and radium-223, on the basis of survival benefit suggested by landmark Phase III trials assessing these agents in this setting. Conversely, although bone-targeted agents (BTAs)—such as the bisphosphonate zoledronic acid and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab—are approved for the prevention of SREs, these compounds have not shown benefit in terms of overall survival. However, emerging evidence has suggested that the combination of BTAs and abiraterone acetate, enzalutamide and the radiopharmaceutical radium-223 could result in improved clinical outcomes and prolonged survival in bone metastatic CRPC. In this review, we will provide an overview on bone tropism of prostate cancer and on the role of BTAs in metastatic hormone-sensitive and castration-resistant prostate cancer.

Heritable and Acquired Thrombophilias in Clinical Practice

Thrombosis is common in clinical practice. Venous thromboembolism in particular raises questions of a possible underlying hereditary or acquired thrombophilic state. Despite considerable data describing the impact of various thrombophilic states on risks of initial and recurrent thromboembolic events, thrombophilia testing is not standardized. An understanding of the utility and pitfalls of clinical thrombophilia testing is necessary to employ this testing properly. When utilized appropriately, thrombophilia testing can be vital in informing an individual patient’s thrombosis risk and pursuing optimal anticoagulant management. Hereditary thrombophilia testing involves investigation for factor V Leiden, the prothrombin G202010A gene mutation, and deficiencies of the natural anticoagulants protein C, protein S, and antithrombin. Assessment for acquired thrombophilias is perhaps even more important, recognizing the possibility for myeloproliferative neoplasms, antiphospholipid antibody syndrome, occult malignancy and other important acquired thrombotic predispositions. Timing of thrombophilia testing in relation to anticoagulation, acute thrombosis, and use of hormonal agents or pregnancy is critical to ensure accurate diagnosis. This review describes each of the most important hereditary and acquired thrombophilias, explains their relationship to venous and arterial thrombosis, delineates evidence-based indications for thrombophilia testing, identifies potential testing pitfalls, and synthesizes the key points in outlining algorithms for thrombophilia testing in clinical practice. This review contains 4 figures, 4 tables, and 48 references. Key words: thrombophilia, venous thromboembolism, pulmonary embolus, deep vein thrombosis, factor V Leiden, prothrombin gene mutation, protein C deficiency, protein S deficiency, antiphospholipid antibody syndrome, hypercoagulability of malignancy

Heritable and Acquired Thrombophilias in Clinical Practice

Thrombosis is common in clinical practice. Venous thromboembolism in particular raises questions of a possible underlying hereditary or acquired thrombophilic state. Despite considerable data describing the impact of various thrombophilic states on risks of initial and recurrent thromboembolic events, thrombophilia testing is not standardized. An understanding of the utility and pitfalls of clinical thrombophilia testing is necessary to employ this testing properly. When utilized appropriately, thrombophilia testing can be vital in informing an individual patient’s thrombosis risk and pursuing optimal anticoagulant management. Hereditary thrombophilia testing involves investigation for factor V Leiden, the prothrombin G202010A gene mutation, and deficiencies of the natural anticoagulants protein C, protein S, and antithrombin. Assessment for acquired thrombophilias is perhaps even more important, recognizing the possibility for myeloproliferative neoplasms, antiphospholipid antibody syndrome, occult malignancy and other important acquired thrombotic predispositions. Timing of thrombophilia testing in relation to anticoagulation, acute thrombosis, and use of hormonal agents or pregnancy is critical to ensure accurate diagnosis. This review describes each of the most important hereditary and acquired thrombophilias, explains their relationship to venous and arterial thrombosis, delineates evidence-based indications for thrombophilia testing, identifies potential testing pitfalls, and synthesizes the key points in outlining algorithms for thrombophilia testing in clinical practice. This review contains 4 figures, 4 tables, and 48 references. Key words: thrombophilia, venous thromboembolism, pulmonary embolus, deep vein thrombosis, factor V Leiden, prothrombin gene mutation, protein C deficiency, protein S deficiency, antiphospholipid antibody syndrome, hypercoagulability of malignancy

Optimising endocrine therapy in postmenopausal women with advanced breast cancer.

Hormone receptor-positive breast cancer is commonly treated with endocrine therapy (ET); however, over time, cancer cells can develop endocrine resistance. This review aims to document combination therapy and sequential therapy in the use of endocrine agents and targeted agents, by conducting two systematic searches using four databases: Cochrane Library, MEDLINE, EMBASE and Web of Science. A total of 26 studies that covered combination therapy were obtained and included for the review. Fourteen were phase III documenting combinations of mechanistic target of rapamycin (mTOR), phosphoinositide-3-kinase (PI3K), vascular endothelial growth factor receptor, human epidermal growth factor receptor 2 and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. The remaining studies were of phase II nature that reported combinations involving inhibitors in mTOR, endothelial growth factor receptor, CDK4/6 and TKI. Interesting findings in inhibitor combinations involving CDK4/6, mTOR and PI3K suggest clinical activity that can overcome endocrine resistance. On the other hand, there were 0 studies that covered sequential therapy. Overall findings showed that combination therapy improved treatment efficacy over monotherapy in postmenopausal patients with hormone receptor-positive advanced breast cancer. Inevitably, the benefits are accompanied with increased toxicity. To optimise ET, further research into combinations and effective patient selection will need to be defined. Additionally, this review warrants future studies to explore sequential therapy.

"Per vaginam" topical use of hormonal drugs in women with symptomatic deep endometriosis: a narrative literature review.

We aim to provide a comprehensive overview of the role of the vagina as a route for drug delivery and absorption, with a particular focus on the use of vaginal hormonal compounds for the treatment of deep infiltrating symptomatic endometriosis. A MEDLINE search through PubMed was performed to identify all published studies in English language on vaginal hormonal treatments for symptomatic endometriosis. Main advantages of the vaginal route include avoidance of the hepatic-first pass metabolic effect, the possibility of using lower therapeutic dosages, and the reduction of side effects compared with the oral administration. Studies on endometriosis treatment mainly focused on the use of vaginal danazol (n=6) and the contraceptive vaginal ring (n=2). One pilot study evaluated the efficacy of vaginal anastrozole in women with rectovaginal endometriosis. Most investigations evaluated the vaginal use of hormonal agents in women with deep infiltrating endometriosis/rectovaginal endometriosis. Overall, a substantial amelioration of pelvic pain symptoms associated with endometriosis was observed, particularly of dysmenorrhea. A significant reduction in rectovaginal endometriotic nodule dimensions measured at ultrasound examination was detected by some but not all authors. The vaginal route represents a scarcely explored modality for drug administration. High local hormonal concentrations might achieve a greater effect on endometriotic lesions compared with alternative routes. Future studies should focus on the use of the vagina for delivering target therapies particularly in patients with deeply infiltrating rectovaginal lesions.

The use of hormonal agents in the treatment of acne.

Hormones and androgens play an important role in the pathogenesis of acne. Multiple hormonal modulators are now available for the treatment of acne. The efficacies and side effects of currently available hormonal agents are reviewed here including the use of oral contraceptives, spironolactone, flutamide, cyproterone acetate, finasteride, and cortexolone 17α-propionate. Hormonal therapies are an efficacious treatment option for acne among females. With the growing need to reduce antibiotic exposures, hormonal therapies should be more widely studied and incorporated into acne treatment strategies.

Clinical benefit of sequential use of endocrine therapies for metastatic breast cancer.

Sequential use of endocrine agents is common in estrogen receptor (ER)-positive metastatic breast cancer (MBC). In premenopausal women with MBC, tamoxifen and/or a luteinizing hormone-releasing hormone (LH-RH) agonist are options for endocrine treatment. Meta-analysis showed that the combination of the two agents is superior to either monotherapy. Under ovarian ablation or function-suppression, an agent used to treat postmenopausal women, such as the aromatase inhibitor (AI), fulvestrant, becomes possible as a subsequent therapy. In postmenopausal women, endocrine treatment options are widely available and an optimal sequence has not yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen, or tamoxifen for patients who have received adjuvant AI. In addition, data suggest that fulvestrant is a promising therapeutic option that has proven efficacy in the treatment of postmenopausal women with MBC. Other agents that may be used in the sequence include a steroidal AI or a progestin. Furthermore, estrogen additive therapy by with diethylstilbestrol or ethinylestradiol has recently been revived and showed a high response rate as a salvage endocrine therapy, although its mechanism of action is still unclear. Thus, sequential use of endocrine therapies, especially the use of a subsequent therapy with a different mechanism of action to the prior therapy, has a beneficial effect in maintaining a good quality of life and extending survival for MBC with hormone responsiveness.

Cerebrovascular Events and Use of NuvaRing

Objective: To report 2 cases, occurring within 1 month at a single institution, in which young women experienced a cerebrovascular event while using the hormonal contraceptive product NuvaRing (etonogestrel/ethinyl estradiol vaginal ring). Case Summary: The first patient presented to the emergency department (ED) with a 10-day history of right frontal headache. A computed tomography (CT) scan and magnetic resonance imaging showed evidence for right postcentral and cortical venous thrombosis. A hypercoagulable workup identified a heterozygous factor V Leiden mutation. The second patient presented to the ED with a same-day history of left frontotemporal headache extending into her left jaw and neck, numbness and clumsiness of right hand and right foot, and inability to make a comprehensible sentence. A CT angiogram showed occlusion of the internal and external carotid arteries. A hypercoagulable workup indicated no evidence of a thrombophilic disorder and a transesophageal echocardiogram indicated no cardioembolic source, resulting in a final diagnosis of a spontaneous carotid artery dissection. Both patients reported recent use of NuvaRing. The medication was discontinued during the hospital stay. Discussion: The use of hormonal agents for contraception carries a well-known risk of venous thrombosis; however, the impact this therapy has on the risk of arterial thrombosis and ischemic brain events is less understood. We found no previous reports of an ischemic brain event in association with NuvaRing use. The Naranjo probability scale indicated a possible relationship between the ischemic events and NuvaRing exposure in both patients. Conclusions: Risk factors should be evaluated appropriately prior to initiating any form of combined hormonal contraceptives, oral or vaginal, in young women.

The role of sexual intercourse in the etiology of carpal tunnel syndrome

The etiology of non-occupational carpal tunnel syndrome is not well understood. It is proposed that carpal tunnel syndrome can develop during sexual intercourse when the hands become repeatedly extended while under pressure from the weight of the upper body. Of the eight risk factors associated with non-occupational carpal tunnel syndrome, age, marital status, pregnancy and use of hormonal agents can be explained by changes in the frequency of sexual intercourse. On the other hand, obesity, macromastia and large chest circumference can be explained by the increased pressure imposed on the wrists by the heavier upper body associated with such conditions. The bilaterality of carpal tunnel syndrome can be explained by the fact that both hands are needed to support the upper body during sexual intercourse. A parallel decrease in the frequency of sexual intercourse and the incidence of carpal tunnel syndrome between the sixth and the seventh decades of life suggests a possible cause and effect relationship between sexual intercourse and carpal tunnel syndrome.

Rational management of endocrine resistance in breast cancer

Endocrine therapy for breast cancer was introduced more than 100 years ago. In the last 30 years, it has been demonstrated that tamoxifen significantly improves outcomes for patients with hormone-responsive breast tumors. Aromatase inhibitors, which suppress the production of estrogen, are recognized today as an effective alternative for estrogen-receptor-positive breast cancer in postmenopausal women. However, despite an initial response to treatment, many tumors eventually recur or progress. When selecting subsequent endocrine therapy, it is helpful to understand the mechanisms of hormone resistance, consider the goals of treatment, and evaluate the clinical potential of each available drug. The objective of this article was to review the underlying mechanisms of action and resistance for each type of hormone therapy, evaluate the most recent data regarding the use of endocrine agents after disease progression or recurrence, and explore potential combinations of hormone therapies with novel molecules that target key growth factor signaling pathways.

Endocrine and targeted manipulation of breast cancer: Summary statement for the Sixth Cambridge Conference

The Sixth Cambridge Conference on Endocrine and Targeted Manipulation of Breast Cancer was convened in Cambridge, Massachusetts on April 30 and May 1, 2007. The purpose of this multidisciplinary meeting of leaders in clinical and basic research and patient treatment was to assess the most recent data in the field, articulate current best practices, and identify the next steps to advance both patient care and research. Topics included a review of data from major recent and ongoing trials of endocrine treatment in patients with early breast cancer and from studies combining endocrine therapy with other treatment. The current status of breast cancer prevention efforts was examined. Preclinical models of response and resistance, initial efforts to profile tumor response and resistance during endocrine therapy in patients, and new developments in pharmacogenomics were also highlighted. In this article, a synopsis of the key issues discussed, conclusions, and recommendations are summarized; these are presented at greater length in the individual articles and accompanying Open Discussions that comprise the full conference proceedings. In the 2 years since the Fifth Conference, we have gained valuable follow-up data from key trials in early breast cancer, which have helped to clarify both the efficacy and safety and tolerability of the available strategies for endocrine therapy. Observations using endocrine agents in combination with other treatment have been similarly extended. More detailed analysis of preclinical models has improved our understanding of resistance to endocrine therapy, and efforts to explore these and other mechanisms in the clinic are now underway. All of this has and continues to contribute to a growing understanding of how to optimize the use of endocrine agents in both treating and preventing breast cancer.

Neoadjuvant Use of Endocrine Therapy in Breast Cancer

Neoadjuvant endocrine therapy is becoming increasingly popular as a safe and effective alternative to chemotherapy in selected patients. Large randomized studies have been published comparing tamoxifen with steroidal and nonsteroidal aromatase inhibitors, with favorable results for aromatase inhibitors letrozole, anastrozole, and exemestane. Endocrine therapy can be used in the neoadjuvant setting for conversion of inoperable breast tumors to operable, and from potential mastectomy to breast-conserving surgery. The use of endocrine agents in this setting also provides an opportunity for the study of their biological effects upon tumor.

Therapeutic options for the management of hot flashes in breast cancer survivors: An evidence-based review

Background: Women with breast cancer may experiencetreatment-induced menopausal symptoms or natural menopause. Menopausal symptoms, particularly hot flashes, are reported at a high frequency in this group and tend to be more severe, distressing, and of greater duration than in controls. Because of the contribution of sex hormones to breast cancer, the use of hormonal agents for the control of hot flashes is problematic in these women. Safer nonhormonal alternatives are recommended for this patient group. Objectives: This was a systematic review of thetherapeutic options for the treatment of hot flashes in breast cancer survivors. Methods: MEDLINE was searched from 1990 to July 2006 using the disease-specific term breast neoplasms and the subheadings menopause and hot flashes. EMBASE was searched from 1990 to March 2006 using the disease-specific subject headings breast tumor/ breast cancer and menopause and the key word hot flashes. The reference lists of the identified articles and relevant review articles were examined for additional publications. Pertinent articles and abstracts of large randomized controlled trials focusing on the treatrment of hot flashes in breast cancer survivors were selected for review. Pilot studies were excluded. Results: A number of nonpharmacologic approaches are available for the treatment of hot flashes in breast cancer survivors, although they appear to be of limited effectiveness. Complementary alternative medicine therapies and vitamin E have been found to have modest effectiveness at best, and data on their long-term safety are not available. Centrally active agents such as the antidepressants venlafaxine and paroxetine and the antiseizure agent gabapentin have shown clinical effectiveness and appear to be reasonably well tolerated in this population. Conclusions: Centrally active agents (eg, venlafaxme, paroxetine, gabapentin) are regarded as the most promising nonhormonal treatments for hot flashes in breast cancer survivors. Nonpharmacologic and complementarylalternative medicine therapies have limited effectiveness.

Hormone therapies in women aged 40 and older: Prevalence and correlates of use

Context The objective of this paper is to report the prevalence and correlates of both prescription and non-prescription hormone use. Design/setting/sample Cross-sectional baseline study from a prospective cohort of 30,448 women receiving mammography in New Hampshire. Main outcome measures Odds of prescription hormone and non-prescription hormone use. Results 29,851 women were included; 62% reported some use of prescription hormone therapy, with current long-term prescription hormone therapy users representing the largest group (25%). Among ever-users, estrogen only was the most commonly used preparation (71% versus 30% for estrogen and progestin combined). Both single agent estrogen and estrogen and progestin combined regimens were taken primarily for treatment of menopausal symptoms or disease prevention. Correlates for prescription hormone use included a family history of breast cancer (associated with decreased use—OR 0.88; 95% CI: 0.84, 0.93), and family history of heart disease (associated with increased use—OR 1.11; 95% CI: 1.06, 1.17). Ten percent of women reported ever use of phytoestrogens (over-the-counter hormones). Family history of breast cancer was a correlate of over-the-counter hormone use (OR 1.10; 95% CI: 1.01, 1.19). Conclusion Management of menopausal symptoms and disease prevention were the main reasons for using prescription hormones, and health histories were important correlates of both prescription and over-the-counter hormone exposures. As evidence changes regarding risks and benefits of hormone exposure, primary care physicians should help women reassess their use of hormonal agents.

Management of hot flashes in breast cancer survivors and men with prostate cancer.

Hot flashes are a significant complaint among many breast cancer survivors and many men undergoing androgen deprivation therapy for prostate cancer. Several therapeutic approaches are available to the suffering man or woman. Many of these individuals have tried nonpharmacologic and nonconventional approaches. However, most nonpharmacologic treatments have not been compared with placebo or were not more effective than placebo in prospective, randomized clinical trials. The most effective nonhormonal treatments for hot flashes include agents from the selective serotonin or noradrenergic reuptake inhibitor (SSRI/SNRI) family. Paroxetine, 10 mg/d, or venlafaxine, 37.5 mg/d, are reasonable initial dosages, and if symptoms do not improve within a week or two, the dosage can be doubled. Gabapentin appears to provide similar benefits, but direct comparisons have not been reported. Because of the strong association between gonadal hormones and breast and prostate cancer, the use of hormonal agents to treat hot flashes in these patients has been limited. However, such hormonal therapies as depomedroxyprogesterone acetate can be prescribed for an informed individual who experiences bothersome symptoms despite nonhormonal treatments.