ArticleLiterature Review

Incidence of management of gynecomastia in men treated for prostate cancer

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Abstract

Gynecomastia is a potentially treatment limiting adverse event in men receiving hormone therapy for prostate cancer. In large, randomized, placebo controlled studies approximately 50% or more of patients with prostate cancer experienced gynecomastia due to multiple mechanisms. Although its severity was mostly reported as mild to moderate, gynecomastia was cited as the reason for most premature withdrawals from therapy. In patients with advanced forms of prostate cancer bilateral orchiectomy was associated with the lowest incidence of gynecomastia, followed by nonsteroidal antiandrogen therapy, diethylstilbestrol and estrogen in rank order. It is important that gynecomastia is well managed in patients with prostate cancer who want to proceed with hormone therapy. Patients should be assessed for the likely etiology of gynecomastia and preventive therapy or treatment for established gynecomastia should be instituted. Prophylactic radiotherapy has been shown to decrease the incidence of hormone induced gynecomastia by more than 50%. An alternative course of action, which may be more convenient for the patient, is the prophylactic use of tamoxifen. Tamoxifen may also mitigate or resolve gynecomastia during its early or proliferative phase. In severe long-standing gynecomastia surgery is warranted since medical therapies are less likely to succeed. Aromatase inhibitors and 4-hydroxytamoxifen are investigational. Gynecomastia is a significant problem in men undergoing hormonal therapy for prostate cancer. It requires prompt recognition, evaluation and management.

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... Both P(H)AHs and ECs are potent AHR and ER agonists, respectively, and these receptors are known to cross-talk and they are regulators of important cellular functions that are involved in various biological processes and have been associated with several patho-physiological conditions [17][18][19]. Some of these compounds have been used as drugs or investigated for therapeutic potential [20][21][22]. Moreover, both classes of compounds are also environmental carcinogens and endocrine disruptors that have generated considerable public health concern [23,24]. ...
... A correlation can be observed between these biological associations suggesting that prolonged or substantial perturbation of these biological functions (Figures 4B and 5B) and physiological systems ( Figures 4C and 5C) by a compound would increase the susceptibility/risk of certain diseases/disorders ( Figures 4D and 5D). Significantly, cancer was listed among the top most (Fisher Exact Test P-value = 1.98610 25 24.76610 22 ) associated disease as most P(H)AHs and some ECs are potent carcinogens. In addition, reproductive system disease, inflammatory disease, hematological disease and neurological disease were significantly associated with both P(H)AHs and ECs as the two classes of compounds are known to affect molecules and functions involved with reproductive system, inflammation, blood and nervous system (Figures 4C-D and 5C-D). ...
... In addition, reproductive system disease, inflammatory disease, hematological disease and neurological disease were significantly associated with both P(H)AHs and ECs as the two classes of compounds are known to affect molecules and functions involved with reproductive system, inflammation, blood and nervous system (Figures 4C-D and 5C-D). Interestingly, the association of psychological disorders with ECs were also significant (P-value = 3.34610 24 23.72610 22 ; Table S6). While it is well-known that estrogen affects mental health [33], the grouping of ESR1 with GPX4, PSMC6, DIABLO, FBXO9, XBP1 homologs which have been associated with bipolar disorder [34,35] suggests that these molecules may also play a role in estrogen-related psychological disorders (Table S6). ...
Article
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The ability to perform large-scale, expression-based chemogenomics on whole adult organisms, as in invertebrate models (worm and fly), is highly desirable for a vertebrate model but its feasibility and potential has not been demonstrated. We performed expression-based chemogenomics on the whole adult organism of a vertebrate model, the zebrafish, and demonstrated its potential for large-scale predictive and discovery chemical biology. Focusing on two classes of compounds with wide implications to human health, polycyclic (halogenated) aromatic hydrocarbons [P(H)AHs] and estrogenic compounds (ECs), we generated robust prediction models that can discriminate compounds of the same class from those of different classes in two large independent experiments. The robust expression signatures led to the identification of biomarkers for potent aryl hydrocarbon receptor (AHR) and estrogen receptor (ER) agonists, respectively, and were validated in multiple targeted tissues. Knowledge-based data mining of human homologs of zebrafish genes revealed highly conserved chemical-induced biological responses/effects, health risks, and novel biological insights associated with AHR and ER that could be inferred to humans. Thus, our study presents an effective, high-throughput strategy of capturing molecular snapshots of chemical-induced biological states of a whole adult vertebrate that provides information on biomarkers of effects, deregulated signaling pathways, and possible affected biological functions, perturbed physiological systems, and increased health risks. These findings place zebrafish in a strategic position to bridge the wide gap between cell-based and rodent models in chemogenomics research and applications, especially in preclinical drug discovery and toxicology.
... ADT beperkt de aanmaak van testosteron, wat de levensverwachting met jaren kan verlengen. De keerzijde is disba-Artikel lans tussen de testosteron-en de oestrogeenspiegel, waardoor gynaecomastie (borstvergroting) en mastodynie (gevoelige borsten) kunnen optreden [2][3][4]. Ter preventie kan een eenmalige korte bestraling van de borstklier worden gegeven, met lichte, voorbijgaande roodheid als bijwerking [5], of dagelijks een tablet tamoxifen voor de duur van de ADT: een van de selectieve oestrogeenreceptormodulatoren, met een anti-oestrogene werking. Hiervan zijn de bijwerkingen opvliegers en transpireren mild, maar tamoxifengebruik kan gepaard gaan met veneuze trombose en cardiovasculaire bijwerkingen [2,4,[6][7][8][9][10]. ...
... Ter preventie kan een eenmalige korte bestraling van de borstklier worden gegeven, met lichte, voorbijgaande roodheid als bijwerking [5], of dagelijks een tablet tamoxifen voor de duur van de ADT: een van de selectieve oestrogeenreceptormodulatoren, met een anti-oestrogene werking. Hiervan zijn de bijwerkingen opvliegers en transpireren mild, maar tamoxifengebruik kan gepaard gaan met veneuze trombose en cardiovasculaire bijwerkingen [2,4,[6][7][8][9][10]. De mannen die in het Reinier de Graaf Gasthuis (RdGG) worden behandeld met ADT maken echter nauwelijks gebruik van deze behandelingen, om onduidelijke redenen. ...
... Een belangrijke bevinding van dit onderzoek is dat ruim een derde van de respondenten gynaecomastie meldt, maar dat de helft van hen dit 'geen probleem' vindt. In de literatuur worden incidenties genoemd van 22-25% [2,4]. Mastodynie is gemeld door 13 respondenten. ...
Article
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Samenvatting In het Reinier de Graaf Gasthuis maken mannen die androgeendeprivatietherapie krijgen vanwege prostaatkanker nauwelijks gebruik van behandelingen ter preventie van gynaecomastie en mastodynie. In een vragenlijstonderzoek is het optreden van gynaecomastie en mastodynie onderzocht, de impact ervan op kwaliteit van leven, de informatieverstrekking erover en redenen om geen preventieve behandelingen te gebruiken. Van de 100 deelnemers (respons 64,1%) ontwikkelde 37,1% gynaecomastie en 13,4% mastodynie. Op vijf na waren alle mannen geinformeerd over deze bijwerkingen. Reden om preventieve behandeling af te wijzen was de vrees voor meer bijwerkingen. Het hebben van bijwerkingen was niet gerelateerd aan de keuze voor een preventieve behandeling (84%). Alle ondervraagden waren goed op de hoogte van de mogelijke bijwerkingen, maar niet van de mogelijke preventieve maatregelen hiertegen. Het vooruitzicht van het krijgen van gynaecomastie en mastodynie lijkt erger dan het hébben van deze bijwerkingen.
... In addition, oestrogen treatment given to prostate cancer patients, that is diethylstilboestrol, a synthetic form of oestrogen, directly stimulates the growth of breast tissue. In both treatment approaches, the resultant outcome is gynaecomastia (Dobs & Darkes, 2005). ...
... If gynaecomastia is present for over a year, it is unlikely to regress substantially, either spontaneously or with medical therapy because of the presence of fibrosis (Braunstein, 2007). In such patients, surgery remains the cornerstone of therapy (Dobs & Darkes, 2005). Complications include haematoma, seroma, infection, sensory changes, pain, breast asymmetry, skin redundancy and scarring. ...
Article
In the management of prostate cancer, gynaecomastia and breast pain can be a significant problem for men treated with hormonal therapy, affecting not just their physical but also their psychological and sexual well-being. Prompt recognition, evaluation and management are therefore essential. Urology nurses involved in the assessment, treatment and follow-up of this patient group across the patient pathway can play a key part in identifying the problem and addressing the issue of gynaecomastia, which may positively affect subsequent patients outcomes. This paper examines the causes, evaluation and current management of gynaecomastia culminating in a case study review.
... The prevalence in males treated with anti-androgen monotherapy is 75%, because drugs are used at high doses (for example 150mg/day bicalutamide), whereas the prevalence is only 15% in males receiving anti-androgen and GnRH analog combination therapy, where the bicalutamide dose is 50 mg/day. [31,32] In these patients, the effectiveness of medical treatment and irradiation (RT) is limited when gynecomastia occurs. The aim of the treatment is therefore to prevent breast development with anti-estrogens or RT. ...
... In one study of the use of Tmx, 69% of prostate cancer patients in the high-dose bicalutamide (150 mg/day) group had gynecomastia, but this was reduced to only 9% in the group receiving both bicalutamide and Tmx (10-20 mg/day). [30,31,32] Tmx must be continued throughout the anti-androgen therapy, since its effects do not persist after it has been discontinued. [33] Anastrozole also reduced anti-androgen related gynecomastia, but was less effective than Tmx. ...
Article
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Gynecomastia is the benign enlargement of male breast glandular tissue and is the most common breast condition in males. At least 30% of males will be affected during their life. Since it causes anxiety, psychosocial discomfort and fear of breast cancer, early diagnostic evaluation is important and patients usually seek medical attention. Gynecomastia was reported to cause an imbalance between estrogen and androgen action or an increased estrogen to androgen ratio, due to increased estrogen production, decreased androgen production or both. Evaluation of gynecomastia must include a detailed medical history, clinical examination, specific blood tests, imaging and tissue sampling. Individual treatment requirements can range from simple reassurance to medical treatment or even surgery. The main aim of any intervention is to relieve the symptoms and exclude other etiological factors.
... Gynecomastia is an abnormal enlargement of male breasts due to hormonal imbalance (increase in estrogens at the expense of testosterone). 1 Gynecomastia is common in men with prostate cancer undergoing antiandrogen therapy with a prevalence as high as 75% when antiandrogen monotherapy is used. [2][3][4] FIGURE 2. 68 Ga-PSMA PET/CT scan shows diffuse intense tracer uptake in the enlarged prostate gland (A, fused PET/CT; B, plain CT). Focal intense tracer concentrating right external iliac lymph node is noted (C, fused PET/CT; D, plain CT). ...
Article
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A 66-year-old man on hormonal therapy with prostate cancer was referred for Ga-PSMA PET/CT scan for biochemical recurrence. Ga-PSMA PET/CT scan detected moderate heterogeneous tracer concentration in bilateral breast parenchyma, in addition to the abnormal tracer concentration in enlarged prostate gland, right external iliac lymph node, and sclerotic lesion in L4 vertebra. On clinical examination, he was found to have bilateral gynecomastia. Abnormal concentration of Ga-PSMA in breast cancer is now well known, and in this context, it is important to know that tracer localization can occur in gynecomastia as well, as evidenced in this case.
... 35,36 The ability of ICI 182,780 to abrogate PRL-induced ductal elongation indicates that ER mediates the growth observed in the current study, overcoming inhibitory signals from testicular androgens. 26,37,38 The ability of PRL to phosphorylate ER-␣ residues that are associated with unliganded activity 29 -31 suggests that PRL-induced activation of ER-␣ itself may be responsible. This action of PRL may be one mechanism underlying the association of circulating PRL with male, as well as female, breast cancer. ...
Article
Male breast cancer is rare and has been the focus of limited research. Although the etiology is unclear, conditions increasing circulating prolactin (PRL), as well as estrogen, increase the risk of tumorigenesis. We modeled exposure to elevated PRL in transgenic mice, using the mammary-selective, estrogen-insensitive promoter neu-related lipocalin (NRL), to drive PRL expression. Male NRL-PRL mice did not develop mammary tumors. However, in cooperation with the well-characterized oncogene transforming growth factor-alpha (TGF-alpha), PRL induced mammary tumors in 100% of male bitransgenic mice. Similar to disease in human males, these tumors expressed variable levels of estrogen receptor-alpha (ER-alpha) and androgen receptors. However, carcinogenesis was not responsive to testicular steroids because castration did not alter latency to tumor development or tumor ER-alpha expression. Interestingly, both NRL-TGF-alpha/PRL and NRL-PRL males demonstrated increased ductal development, which occurred during puberty, similar to female mice. This outgrowth was diminished in NRL-PRL males treated with ICI 182,780, suggesting that PRL enhances ER-mediated growth. Treatment of MCF-7-derived cells with PRL increased phosphorylation of ER-alpha at residues implicated in unliganded ER-alpha activity. Together, these studies suggest that PRL expands the pool of cells susceptible to tumorigenesis, which is then facilitated by PRL and TGF-alpha cross talk. Activation of ER-alpha is one mechanism by which PRL may contribute to breast cancer and points to other therapeutic strategies for male patients.
... We included and grouped hot flashes and breast problems because of their high prevalence, accompanying bother, and frequent need for symptomatic treatment in patients undergoing androgen deprivation therapy. [8][9][10][11] The EPIC-CP scoring system-We designed EPIC-CP so that symptom scores for each domain (urinary incontinence, urinary irritative/obstructive, bowel, sexual, and vitality/ hormonal) are calculated similarly as is done with the AUA-SI/IPSS, 5 (i.e. higher scores reflect worse symptom/bother severity) by simply adding together the numeric values (0 to 4) that correspond to patient responses in each of 3 questions comprising each HRQOL domain ( Figure 1). Consequently, the minimum symptom score (best HRQOL) = 0 and the maximum symptom score (worst HRQOL) = 12 in each domain. ...
Article
Measuring the health related quality of life of patients with prostate cancer in routine clinical practice is hindered by the lack of instruments enabling efficient, real-time, point of care scoring of multiple health related quality of life domains. Thus, we developed an instrument for this purpose. The Expanded Prostate Cancer Index Composite for Clinical Practice is a 1-page, 16-item questionnaire that we constructed to measure urinary incontinence, urinary irritation, and the bowel, sexual and hormonal health related quality of life domains. We eliminated conceptually overlapping items from the 3-page Expanded Prostate Cancer Index Composite-26 and revised the questionnaire format to mirror the AUA symptom index, thereby enabling practitioners to calculate health related quality of life scores at the point of care. We administered the Expanded Prostate Cancer Index Composite for Clinical Practice to a new cohort of patients with prostate cancer in community based and academic oncology, radiation, and urology practices to evaluate instrument validity as well as ease of use in clinical practice. A total of 175 treated and 132 untreated subjects with prostate cancer completed the Expanded Prostate Cancer Index Composite for Clinical Practice. The domain scores of the Expanded Prostate Cancer Index Composite for Clinical Practice correlated highly with the respective domain scores from longer versions of the Expanded Prostate Cancer Index Composite (r≥0.93 for all domains). The Expanded Prostate Cancer Index Composite for Clinical Practice showed high internal consistency (Cronbach's α 0.64-0.84) and sensitivity to prostate cancer treatment related effects (p<0.05 in each of 5 health related quality of life domains). Patients completed the Expanded Prostate Cancer Index Composite for Clinical Practice efficiently (96% in less than 10 minutes and with 11% missing items). It was deemed very convenient by clinicians in 87% of routine clinical encounters and clinicians accurately scored completed questionnaires 94% of the time. The Expanded Prostate Cancer Index Composite for Clinical Practice is a valid instrument that enables patient reported, health related quality of life to be measured efficiently and accurately at the point of care, and thereby facilitates improved emphasis and management of patient reported outcomes.
... Antiandrogen therapy (AT) has substantially improved outcome of prostate cancer treatment; however, a negative side effect is that gynecomastia develops in 60-70% of patients [24]. Swelling, pain, and disfigurement may have a serious impact on quality of life [6,27]. This issue is of increasing clinical relevance as AT plays a growing role in adjuvant, curative, and palliative therapy of localized, locally advanced, and metastasized prostate cancer and is often recommended for several years [28]. ...
Article
Full-text available
Gynecomastia is a frequent side effect of antiandrogen therapy for prostate cancer and may compromise quality of life. Although it has been successfully treated with radiotherapy (RT) for decades, the priority of RT as a preferred treatment option has recently been disputed as tamoxifen was also demonstrated to be effective. The aim of the present paper is to provide an overview of indications, frequency, and technique of RT in daily practice in Germany, Switzerland, and Austria. On behalf of the DEGRO-AG GCG-BD (German Cooperative Group on Radiotherapy of Benign Diseases) a standardized questionnaire was sent to 294 RT institutions. The questionnaires inquired about patient numbers, indications, RT technique, dose, and - if available - treatment results. Moreover, the participants were asked whether they were interested in participating in a prospective study. From a total of 294 institutions, 146 replies were received, of which 141 offered RT for gynecomastia. Seven of those reported prophylactic RT only, whereas 129 perform both preventive and symptomatic RT. In 110 of 137 departments, a maximum of 20 patients were treated per year. Electron beams (76%) were used most often, while 24% of patients received photon beams or orthovolt x-rays. Total doses were up to 20 Gy for prophylactic and up to 40 Gy for therapeutic RT. Results were reported by 19 departments: prevention of gynecomastia was observed in 60-100% of patients. Only 13 institutions observed side effects. Prophylactic and symptomatic RT is widely used in the German-speaking countries, but patient numbers are small. The clinical results indicate that RT is a highly effective and well-tolerated treatment.
... It results from an excess of stimulatory estrogenic influences over inhibitory androgenic effects on the breast. Although there are many known causes of gynecomastia, most cases are idiopathic [2]. In the literature, only a few cases of gynecomastia have been reported showing increased gallium uptake in the breasts [3,4]. ...
Article
Gallium-67 (67 Ga) is a radioisotope that has been used for many years to detect inflammation or neoplasm. Its definite mechanism is still unclear. However, it has been noted that in certain physiological situations, 67 Ga can accumulate in some sites. In this study, we report a case of gynecomastia with 67 Ga accumulation. We also briefly review articles that proposed some mechanisms which might contribute to the phenomenon, including estrogen overproduction and lactoferrin production.
... Hormone-based therapies or androgen deprivation therapy (ADT) are being increasingly used in patients with PCa as less morbid alternatives to surgical castration. PCa patients who receive ADT appear to be at increased risk for gynecomastia with a prevalence as high as 75% [97]. Gynecomastia is characterized by abnormally enlarged male breasts by reason of hormonal imbalance (increase in estrogens at the expense of testosterone) [98]. ...
Article
Full-text available
There is now an increasing trend for targeting cancers to go beyond early diagnosis and actually improve Progression-Free Survival and Overall Survival. Identifying patients who might benefit from a particular targeted treatment is the main focus for Precision Medicine. Radiolabeled ligands can be used as predictive biomarkers which can confirm target expression by cancers using positron emission tomography (PET). The same ligand can subsequently be labeled with a therapeutic radionuclide for targeted radionuclide therapy. This combined approach is termed “Theranostics”. The prostate-specific membrane antigen (PSMA) has emerged as an attractive diagnostic and therapeutic target for small molecule ligands in prostate cancer. It can be labeled with either positron emitters for PET-based imaging or beta and alpha emitters for targeted radionuclide therapy. This review article summarizes the important concepts for Precision Medicine contributing to improved diagnosis and targeted therapy of patients with prostate cancer and we identify some key learning points and areas for further research.
... Even though the actions of androgens are believed to oppose that of estrogens, the inhibitory effect of androgens on breast tissue depends largely on the relative tissue concentrations of both types of hormones as well as their receptor-mediated actions. This conclusion is consistent with two observations: (1) breasts do not undergo normal development in girls diagnosed with androgen-secreting adrenal tumors despite adequate circulating estrogens [68] and (2) development of gynecomastia in men treated with AR blockers for prostate cancer [69]. Clinically, a possible link has been established between AR expression and outcomes in certain subsets of breast cancer [70,71]. ...
Article
Full-text available
Classification of breast cancer as endocrine sensitive, hormone dependent, or estrogen receptor (ER) positive refers singularly to ER α . One of the oldest recognized tumor targets, disruption of ER α -mediated signaling, is believed to be the mechanistic mode of action for all hormonal interventions used in treating this disease. Whereas ER α is widely accepted as the single most important predictive factor (for response to endocrine therapy), the presence of the receptor in tumor cells is also of prognostic value. Even though the clinical relevance of the two other sex hormone receptors, namely, ER β and the androgen receptor remains unclear, two discordant phenomena observed in hormone-dependent breast cancers could be causally related to ER β -mediated effects and androgenic actions. Nonetheless, our understanding of regulatory molecules and resistance mechanisms remains incomplete, further compromising our ability to develop novel therapeutic strategies that could improve disease outcomes. This review focuses on the receptor-mediated actions of the sex hormones in breast cancer.
... Mastodynia can be mild or extremely painful and can cause the breast and nipples to be very sensitive to the touch. Determining an incidence rate of gynecomastia among prostate cancer patients treated with ADT can be a challenge to ascertain since idiopathic gynecomastia is common in the elderly male population (Dobs & Darkes, 2005). The anti-androgen bicalutamide (Casodex) was examined in two large randomized, double-blinded, placebo, clinical trials to determine its effectiveness in treating advanced prostate cancer (See et al., 2002;Wirth et al., 2001). ...
Article
Advanced prostate cancer patients treated with androgen deprivation therapy (ADT) have been shown to experience a large number of physiological and psychological sequelae; however, few studies have examined how these sequelae affect the patients??? and their partners??? quality of life (QOL). PURPOSE: The purposes of this study were: 1) to describe and compare patients??? and partners??? levels of self-efficacy, symptom distress, communication, appraisal, coping and QOL and 2) to determine if specific antecedent factors (self-efficacy, symptom distress, communication, their partners??? QOL), and mediators (appraisal of illness/caregiving, active and avoidant coping) explain a significant amount of variance in the QOL of advanced prostate cancer patients treated with ADT and their partners. THEORETICAL FRAMEWORK: The study was guided by a stress-coping model. METHODS: The study was a cross-sectional, secondary analysis of data obtained from two randomized clinical trials. The study sample consisted of 75 patient-partner dyads. Data were obtained using standardized measures with acceptable reliabilities. Independent t tests were used to assess differences between patients and partners scores on major study variables. Bootstrapping was used to assess for mediator effects and structural equation modeling was used to assess the the models function to predict QOL. RESULTS: Patients and partners were more alike than different. Partners reported worse emotional QOL than patients. Patients and partners had poorer emotional QOL when compared to an age and gender matched normative sample. Appraisal (illness/caregiving) and avoidant coping were significant mediators between antecedents variables and QOL for both patients and partners. Partners??? QOL was a significant predictor of patients??? QOL. Patients??? QOL was not a significant predictor of partners??? QOL. Overall, the stress-coping model accounted for a significant amount of variance in patients??? and partners??? QOL (89% and 74%, respectively). CONCLUSIONS: Findings suggest that advanced prostate cancer patients treated with ADT and their partners are at risk for poorer emotional QOL. Results also indicate that there are a number of potential areas for interventions to improve patients??? and partners??? emotional QOL: self-efficacy, symptom distress, communication, appraisal and avoidant coping.
... Hormone-based therapies or androgen deprivation therapy (ADT) are being increasingly used in patients with PCa as less morbid alternatives to surgical castration. PCa patients who receive ADT appear to be at increased risk for gynecomastia with a prevalence as high as 75% [97]. Gynecomastia is characterized by abnormally enlarged male breasts by reason of hormonal imbalance (increase in estrogens at the expense of testosterone) [98]. ...
... A detailed history should include the onset and duration of the breast enlargement, pain or tenderness, weight loss or gain, nipple discharge, virilization, medication history, and family history of gynecomastia which may suggest androgen insensitivity syndrome, familial aromatase excess or sestoli cell tumours. Physical examination should differentiate between true gynecomastia and pseudogynecomastia and should include signs of tomours, liver and kidney diseases, or hyperthyroidism and should also include genital examination [5,6,[25][26][27][28][29][30][31]. ...
Article
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p>Gynecomastia, referred to enlargement of the male’s breast tissue is a common finding in boys during childhood. Although most cases are benign and self-limited, it may be a sign of an underlying systemic disease or even drug induced. Rarely, it may represent male breast cancer. Understanding its pathogenesis is crucial to distinguish a normal developmental variant from pathological cases.This review will highlight the pathophysiology, etiology, diagnosis and various medical and surgical therapies.</p
... Gynecomastia is the result of an imbalance between estrogens and androgens in breast tissue with a high level of estrogen causing the growth of the breast tissue. [19,20] Although localization of 68 Ga-labeled PSMA in the breast parenchyma has been well documented in the neovasculature of breast cancer, it is essential to know that PSMA expression is also seen in gynecomastia [ Figure 4]. [21,22] ...
Article
Full-text available
Ga-labeled prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography imaging (PET/CT) is a rapidly evolving imaging modality for prostate cancer. Many studies have proved its superiority in staging, restaging, and detecting the recurrent prostate cancer. However, case reports describing the incidental tracer uptake in benign and nonprostatic malignancies are also reported in the literature, thus questioning the specificity of the tracer. This pictorial assay illustrates the nonspecific tracer uptake encountered during PSMA PET/CT imaging, knowledge of which can increase the confidence of interpreting physicians and may also open a new path for peptide receptor radionuclide therapy in nonprostatic malignancies. © 2018 Indian Journal of Nuclear Medicine | Published by Wolters Kluwer - Medknow.
... Long-standing gynecomastia resulting from the fibrotic changes in the adipose tissue appears to be best managed by surgery [25]. However, breast surgery can be associated with complications such as doughnut deformity, nipple necrosis, nipple flatting, and loss of sensation [26]. ...
Article
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AimTo provide an overview on the available treatments to prevent and reduce gynecomastia and/or breast pain caused by antiandrogen therapy for prostate cancer.Methods The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published and assessed the validity of the information on efficacy and treatment-related toxicity.ResultsEight randomized controlled trials and one meta-analysis were identified. Two randomized trials demonstrated that prophylactic radiation therapy (RT) using 1 × 10 Gy or 2 × 6 Gy significantly reduced the rate of gynecomastia but not breast pain, as compared to observation. A randomized dose-finding trial identified the daily dose of 20 mg tamoxifen (TMX) as the most effective prophylactic dose and another randomized trial described that daily TMX use was superior to weekly use. Another randomized trial showed that prophylactic daily TMX is more effective than TMX given at the onset of gynecomastia. Two other randomized trials described that TMX was clearly superior to anastrozole in reducing the risk for gynecomastia and/or breast pain. One comparative randomized trial between prophylactic RT using 1 × 12 Gy and TMX concluded that prophylactic TMX is more effective compared to prophylactic RT and furthermore that TMX appears to be more effective to treat gynecomastia and/or breast pain when symptoms are already present. A meta-analysis confirmed that both prophylactic RT and TMX can reduce the risk of gynecomastia and/or breast pain with TMX being more effective; however, the rate of side effects after TMX including dizziness and hot flushes might be higher than after RT and must be taken into account. Less is known regarding the comparative effectiveness of different radiation fractionation schedules and more modern RT techniques.Conclusions Prophylactic RT as well as daily TMX can significantly reduce the incidence of gynecomastia and/or breast pain. TMX appears to be an effective alternative to RT also as a therapeutic treatment in the presence of gynecomastia but its side effects and off-label use must be considered.
... Although it is one of the leading breast symptoms for which women seek medical attention, it is believed that mastalgia may be generally underreported and under-studied (9)(10)(11)(12)(13)(14). Complaints of mastalgia are more common in premenopausal women than in those aged older than 60 years, in patients with larger breast cup size, and in patients with lower fitness and activity levels (15,16). For men, breast pain is uncommon, although it may occur in the setting of gynecomastia, hormonal imbalance, and other conditions (14,17,18). Breast pain can also present in transgender individuals. ...
Article
Over two-thirds of women will experience breast pain in their lifetime. As one of the leading breast symptoms for which women seek medical attention, breast pain is suspected to be underreported and under-studied. Cyclical breast pain is related to hormonal changes. Noncyclical breast pain is independent of the menstrual cycle and can be idiopathic and related to chronic pain syndromes, infections, ill-fitting bras, musculoskeletal abnormalities, pregnancy, perimenopause, and postsurgical causes. Breast pain can also present in transgender patients and may require additional considerations as to the underlying cause. Imaging of mastalgia depends upon the suspected etiology. Inappropriate imaging for breast pain is associated with significant utilization of health care resources. Cyclical breast pain does not require an imaging work-up. The work-up of focal, noncyclical breast pain includes ultrasound for women aged younger than 40 years, and mammography and ultrasound for women aged 40 years and older. Management of breast pain is often supportive, as most breast pain resolves spontaneously. If pain persists, imaging and management should follow a step-wise approach. If conservative measures fail, second-line therapy is topical nonsteroidal anti-inflammatory drugs. If breast pain is severe and resistant to conservative methods, additional third-line therapies can be added by breast care specialists with specific knowledge of the potential deleterious side effects of these medications. While the causes of mastalgia are overwhelmingly benign, breast pain can significantly impact quality of life, and the breast radiologist should be familiar with causes, management, and treatment recommendations from a multidisciplinary approach.
... In accordance with these results, the use of SERMs is not justified for the treatment of GM with the possible exception of tamoxifen in cases of painful GM of recent onset as it offers rapid relief from pain, regardless of the magnitude of response. In contrary, there is a substantial body of evidence that supports the use of SERMs or AIs for the prevention of GM in patients with prostate cancer undergoing AAT (Boccardo et al., 2005;Dobs & Darkes, 2005). An alternative modality is low-dose prophylactic radiotherapy (PRT) (Dicker, 2003), which, although less effective, is more practical, as few short-term applications are required. ...
Article
Background Gynecomastia (GM) is a benign proliferation of the glandular tissue of the breast in men. It is a frequent condition with a reported prevalence of 32–65%, depending on the age and the criteria used for definition. GM of infancy and puberty are common, benign conditions resolving spontaneously in the majority of cases. GM of adulthood is more prevalent among the elderly and proper investigation may reveal an underlying pathology in 45–50% of cases. Objectives The aim was to provide clinical practice guidelines for the evaluation and management of GM. Materials and methods A literature search of articles in English for the term ‘gynecomastia’ was conducted. Evidence‐based recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Results A set of five statements and fifteen clinical recommendations was formulated. Conclusions The purpose of GM assessment should be the detection of underlying pathological conditions, reversible causes (administration/abuse of aggravating substances), and the discrimination from other breast lumps, particularly breast cancer. Assessment should comprise a thorough medical history and physical examination of the breast and genitalia (including testicular ultrasound). A set of laboratory investigations may integrate the evaluation: testosterone (T), estradiol (E2), sex hormone‐binding globulin (SHBG), luteinizing hormone (LH), follicular stimulating hormone (FSH), thyroid stimulating hormone (TSH), prolactin, human chorionic gonadotropin (hCG), alpha‐fetal protein (AFP), liver and renal function tests. Breast imaging may be used whenever the clinical examination is equivocal. In suspicious lesions, core needle biopsy should be sought directly instead. Watchful waiting is recommended after treatment of underlying pathology or discontinuation of substances associated with GM. T treatment should be offered to men with proven T deficiency. The use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and non‐aromatizable androgens is not justified in general. Surgical treatment is the therapy of choice for patients with long‐lasting GM. Summary of Statements (S) and Recommendations (R) • S1. Gynecomastia (GM) is a benign proliferation of glandular tissue of the breast in males. • S2. GM of infancy is a common condition that usually resolves spontaneously, typically within the first year of life. • S3. GM of puberty is a common condition, affecting approximately 50% of mid‐pubertal boys; in more than 90% of cases, it resolves spontaneously within 24 months. • S4. The prevalence of GM in adulthood increases with increasing age; proper investigation may reveal an underlying pathology in approximately 45–50% of the cases. • S5. Male breast cancer is rare; GM should not be considered a premalignant condition. The following recommendations are divided into ‘strong’, denoted by the number 1 and associated with the terminology ‘we recommend’, and ‘weak’ denoted by the number 2 and associated with the phrase ‘we suggest’. The grading of the quality of evidence is denoted as follows: ⊕○○○ for very low‐quality evidence; ⊕⊕○○ for low quality; ⊕⊕⊕○ for moderate quality; and ⊕⊕⊕⊕ for high quality. • R1. The presence of an underlying pathology should be considered in GM of adulthood. We recommend that the identification of an apparent reason for GM in adulthood, including the use of medication known to be associated with GM, should not preclude a detailed investigation (1 ⊕⊕⊕○). • R2. We suggest that the initial screening to rule out lipomastia, obvious breast cancer, or testicular cancer might be performed by a general practitioner or another non‐specialist (2 ⊕○○○). • R3. We recommend that in those cases where a thorough diagnostic workup is warranted, it should be performed by a specialist (1 ⊕○○○). • R4. We recommend that the medical history should include information on the onset and duration of GM, sexual development and function, and administration or abuse of substances associated with GM (1 ⊕⊕⊕○). • R5. We recommend that the physical examination should detect signs of under‐virilization or systemic disease (1 ⊕⊕⊕⊕). • R6. We recommend that breast examination should confirm the presence of palpable glandular tissue to discriminate GM from lipomastia (pseudo‐gynecomastia) and rule out the suspicion of malignant breast tumor (1 ⊕⊕⊕⊕). • R7. We recommend that the physical examination should include the examination of the genitalia to rule out the presence of a palpable testicular tumor and to detect testicular atrophy (1 ⊕⊕⊕⊕). • R8. We recommend that genitalia examination is aided by a testicular ultrasound, as the detection of a testicular tumor by palpation has low sensitivity (1 ⊕⊕○○). • R9. We suggest that a set of evaluations may include T, E2, SHBG, LH, FSH, TSH, prolactin, hCG, AFP, and liver and renal function tests (2 ⊕⊕○○). • R10. We suggest that breast imaging may offer assistance, where the clinical examination is equivocal (2 ⊕⊕○○). • R11. We suggest that, if the clinical picture is suspicious for a malignant lesion, core needle biopsy should be performed (2 ⊕⊕○○). • R12. We recommend watchful waiting after treatment of underlying pathology or discontinuation of the administration/abuse of substances associated with GM (1 ⊕⊕○○). • R13. We recommend that T treatment should be offered only to men with proven testosterone deficiency (1 ⊕⊕⊕○). • R14. We do not recommend the use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or non‐aromatizable androgens in the treatment of GM in general (1 ⊕⊕○○). • R15. We suggest surgical treatment only for patients with long‐lasting GM, which does not regress spontaneously or following medical therapy. The extent and type of surgery depend on the size of breast enlargement, and the amount of adipose tissue (2 ⊕⊕○○).
... This can be prevented by prophylactic irradiation to the breast at a dose of 4-6 Gy either as a single or divided doses. Established gynecomastia is difficult to treat but may be managed with external irradiation to prevent further progression or by subcutaneous mastectomy [23][24]. Liver toxicity with deranged liver function test (LFT) results was seen in two patients. ...
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... Hier empfiehlt es sich, nach oben beschriebener Diagnostik und Befunddokumentation einen entsprechenden Bericht an den Medizinischen Dienst der zuständigen Krankenversicherung zu formulieren.Eine Sonderstellung nimmt die Behandlung der Gynäkomastie ein, die mit der the- rapeutischen Androgen-Deprivation bei fortgeschrittenem Prostata-Karzinom auf- tritt. Zum Einsatz kommen prophylatische Radiatio sowie Aromatasehemmer oder Tamoxifen (Dobs u.Darkes 2005;Carlson 2011). Hierbei scheint die tägliche Gabe von Tamoxifen die beste Wirkung zu entfalten (Bedognetti et al. 2010). ...
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Chapter
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Gynae means ‘woman’ and mastos means ‘breast’ in Greek. Gynaecomastia is essentially the presence of excessive breast tissue in a male that gives the appearance of having actual breasts. Gynaecomastia affects men of all ages but is more commonly found in teenage boys and older men. It can affect either one or both breasts. It is an important area of men's health as gynaecomastia can cause physical embarrassment and psychological distress to the individual and can be a marker of serious underlying disease. This article reviews the assessment and management of patients presenting with gynaecomastia in primary care.
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Gynecomastia is a pathological enlargement of male breasts due to hormonal imbalance and elevation of estrogens at the expense of testosterone. It is very important to diagnose this disease precociously because it can be the expression of different underlying pathologies. Besides genetic, chromosomal or chronic diseases, drugs often represent the principal cause of this hormonal disequilibrium. In the elderly population, antiandrogen therapy for prostate cancer frequently induces gynecomastia, thus negatively affecting the patients' compliance to treatment because of physical and psychological discomfort deriving from this condition; gynecomastia can in fact be associated with severe breast pain, and it can modify how patients see their own body. During the past decades and even today, many different surgical, radiotherapeutic or clinical approaches have been proposed to prevent or treat this hypertrophy. This article focuses on gynecomastia associated with antiandrogen-based hormonal treatment and shortly reviews the currently most often used therapeutic options for preventing and treating this pathology.
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Gynecomastia, defined as benign proliferation of glandular breast tissue has a prevalence of 32% to 72% in the male. In the urology setting, it is associated to patients with prostate cancer and hormone treatment with a prevalence of 15% in the case of complete hormone blockage and 75% in monotherapy. The different options of treatment in prostate cancer have changed in recent decades. Thus, we have focused on this subject to evaluate the different therapy options of hormone manipulation induced gynecomastia in prostate cancer patients. To synthesize the available evidence on the different therapeutic options in prostate cancer patients who develop gynecomastia due to the use of nonsteroidal antiandrogens and to generate a diagnostic algorithm and treatment. Using the PICO type structured search strategy (Patient or problem, Intervention, Comparison, Outcome or result) in the data bases of PubMed-Medline and Cochrane, identification was made of the relevant studies related to the treatment of gynecomastia in Prostate Cancer patients treated with nonsteroidal antiandrogens. We have found 3 possible therapeutic options for the treatment of gynecomastia and mastodynia in patients with hormone deprivation therapy for prostate cancer. The 10Gy radiotherapy would be an option for the treatment of gynecomastia, although not all the patients need prophylactic treatment since only 50% report moderate-severe discomfort. Another option is the use of drugs such as tamoxifen 20mg/day that lead to a significant decrease in the mammary effects. Gynecomastia and mastodynia, given their high incidence, make the physical examination a fundamental tool for all patients before initiating treatment with antiandrogens. The use of tamoxifen 20mg/day is the best treatment and prevention option against gynecomastia and mastodynia, while in the case of long-course established gynecomastia, surgery is the gold standard.
Article
The role of estrogens in male sexual function and the pathogenesis of testosterone deficiency remain controversial and poorly understood. To review the distribution of estrogens in normal and testosterone deficient men, their potential role in sexual function, and the clinical implications of elevated estrogens during testosterone therapy. A comprehensive, broad-based literature review was conducted on the role of estrogens in male sexual function and testosterone deficiency. Estrogens elicit a variety of physiological responses in men and may contribute to modulation of sexual function. In the absence of testosterone deficiency, elevations in estrogens do not appear to be harmful and estrogens may help maintain some, but not all, sexual function in castrated men. While the therapeutic use of estrogens at pharmacologic doses has been used to suppress serum testosterone, naturally occurring elevations of estrogens do not appear to be a cause of low testosterone. During testosterone replacement, estrogens may rise and occasionally reach elevated levels. There is a lack of evidence that treatment of elevated estrogen levels during testosterone replacement has benefit in terms of male sexuality. Further research on the importance of estrogens in male sexual function is needed. Current evidence does not support a role of naturally occurring estrogen elevations in testosterone deficiency or the treatment of elevated estrogens during testosterone therapy.
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An imbalance between estrogen action relative to androgen action at the breast tissue level results in gynecomastia. Enhancement of aromatization of androgens to estrogens is important in the pathogenesis of gynecomastia associated with obesity, aging, puberty, liver disease, thyrotoxicosis, 17-oxosteroid reductase deficiency. Klinefelter's syndrome, and neoplasms of the testes, adrenals and liver. A primary aromatase excess syndrome with exuberant gynecomastia had been found both sporadically and in a familial setting. Although aromatase inhibition would appear to be an important class of drugs to treat gynecomastia, relatively little published data with these drugs exist and most concern the use of delta1-testolactone, which reduces the size of the breast glandular tissue, but does not completely ameliorate the problem. Studies with the newer generation of more potent aromatase inhibitors need to be carried out.
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Current hormonal therapies for prostate cancer are associated with significant morbidities, including symptoms of andropause and osteoporosis. Oral estrogens prevented many of these problems but were abandoned due to cardiovascular toxicity attributed to hepatic effect. In contrast, parenteral estrogens prevent first pass hepatic metabolism and substantially reduce cardiovascular risk, and long-term transdermal estradiol therapy is believed to be cardioprotective. We report preliminary results of a pilot study using transdermal estradiol therapy to treat men with advanced prostate cancer. A total of 20 patients with advanced prostate cancer were enrolled in a before and after study that examined the impact of estradiol patches on hormones, disease, thrombophilia, vascular flow, osteoporosis and quality of life. Median followup is 15 months. Estradiol levels greater than 1,000 pmol./l. were achieved using 2 patches and higher levels were obtained by increasing the number of patches. All patients achieved castrate levels of testosterone within 3 weeks and had biochemical evidence of disease regression. One patient died of disease at 14 months and 1 cardiovascular complication occurred. Thrombophilic activation was avoided and vascular flow improved. Bone mineral density was significantly increased. Mild or moderate gynecomastia occurred in 80% of patients but no patient had hot flushes. All other functional and symptomatic quality of life domains improved. Transdermal estradiol therapy produced an effective tumor response. Cardiovascular toxicity was substantially reduced compared with that expected of oral estrogen, and other morbidity (gynecomastia) was negligible. Transdermal estradiol therapy prevented andropause symptoms, improved quality of life scores and increased bone density. Transdermal estradiol costs a tenth of current therapy cost, with the potential for considerable economic savings over conventional hormone therapies.
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The purpose of the present work has been to evaluate surgical treatment of gynecomastia performed by liposuction combined with subcutaneous mastectomy. It was designed as a prospective consecutive registration of 21 patients (28 breasts) operated in a four month period. Treatment was done in local anaesthesia in the out-patient clinic. Treatment was in one patient complicated with a haematoma. In 86% of cases the patients were satisfied with the postoperative result. Liposuction combined with surgical excision of the gland performed as an out-patient treatment in local anaesthesia is followed by few complications and good cosmetic results.
Article
Objectives: This prospective, randomized phase III study was initiated to compare the efficacy and side effects of bilateral orchiectomy versus a combination of a luteinizing hormone-releasing hormone agonist depot formulation, goserelin acetate (3.6 mg s.c. once every 4 weeks) and flutamide (250 mg 3× daily) in patients with metastatic prostate cancer. Methods: Relative treatment efficacy was assessed by comparing the two treatment groups with respect to response, time to first progression, progression-free survival, duration of survival and time to death due to malignant disease. Results: There was a difference in response only with respect to a more frequent decrease to normal of the serum prostate acid phosphatase in patients assigned to maximal androgen blockade treatment. Additionally, maximal androgen blockade treatment showed significantly better results for duration of survival (p = 0.04), time to death due to malignant disease (p = 0.008), time to first progression (p = 0.009) and progression-free survival (p = 0.02). The most frequent side effects for both treatments included hot flushes and gynaecomastia. Conclusions: Increased time to progression and duration of survival is achieved by the combination of flutamide and goserelin when compared to bilateral orchiectomy.
Article
A study of the effects of irradiation in prevention of gynaecomastia due to oestrogen therapy for carcinoma is reported. Twenty patients were treated with oestrogens without radiotherapy, of these 17 developed gynaecomastia. Twenty-seven patients were treated with radiotherapy prior to oestrogens, of these only 3 developed gynaecomastia. Previous studies have shown similar results but have used larger doses of irradiation and recommended a delay of 1 month between radiotherapy and treatment. We have used a low dose of radiation and started oestrogens immediately after radiotherapy.
Article
We have evaluated the efficacy of the antiestrogen tamoxifen in six men with painful idiopathic gynecomastia. Subjects were given either tamoxifen or placebo for 2 to 4 months and then were given the other agent for an identical period. Breast size was considered to have been reduced only if it had decreased by one or more Marshall-Tanner stages during the treatment period. Pain reduction with tamoxifen therapy was statistically significant for the group, occurring in five of six subjects during tamoxifen treatment and in only one of six during the placebo period. Size reduction with tamoxifen was only marginally significant for the entire group, but occurred in all three subjects who were initially in Marshall-Tanner stage III and in none of the three subjects who were initially in stage V. During tamoxifen treatment, there was a significant increase in the serum levels of luteinizing hormone and total estradiol and a marginally significant increment in the total testosterone level.
Article
The authors describe the abnormalities of gonadal function developing in a patient with prostate cancer who had received estrogen therapy continuously for 6 years. The pretreatment prostate biopsy showed well developed acini consistent with normal androgenization and adenocarcinoma. Twelve years later, 6 years after discontinuation of estrogen treatment, the patient presented with severe hypogonadism, gynecomastia, and primary hypothyroidism. Testicular biopsies showed ghosts of seminiferous tubules with absence of Leydig cells, and prostatic biopsies showed atrophic acini without evidence of malignancy. Despite undetectable serum testosterone levels, serum gonadotropins were inappropriately normal and responded minimally to gonadotropin-releasing hormone (GnRH) administration. Replacement therapy with levothyroxine did not correct gonadal dysfunction. Thus, prolonged estrogen therapy may result in irreversible testicular destruction and loss of the feed-back response of the hypothalamic pituitary gonadal axis.
Article
Benign asymptomatic or painful enlargement of the male breast is a common problem, postulated to be due to an increased estrogen/testosterone ration or due to increased estrogenic or decreased androgenic stimulation via estrogen or androgen receptor interactions. Treatment at present consists of analgesic medication or surgery. However, treatment directed against the preponderance of estrogenic stimulation would seem to represent a more specific form of therapy. In the present double-blind crossover study, one-month courses of a placebo or the antiestrogen tamoxifen (10 mg given orally bid) were compared in random order. Seven of ten patients experienced a decrease in the size of their gynecomastia due to tamoxifen (P less than 0.005). Overall, the decrease for gynecomastia for the whole group was significant (P less than 0.01). There was no beneficial effect of placebo (P greater than 0.1). Additionally, all four patients with painful gynecomastia experienced symptomatic relief. There was no toxicity. The reduction of breast size was partial and may indicate the need for a longer course of therapy. A followup examination was performed in eight out of ten patients nine months to one year after discontinuing placebo and tamoxifen. There were no significant changes from the end of the initial study period except for one tamoxifen responder who developed a recurrence of breast tenderness after six months, and one nonresponder who demonstrated an increase in breast size and a new onset of tenderness after ten months. Therefore, antiestrogenic treatment with tamoxifen may represent a safe and effective mode of treatment for selected cases of cosmetically disturbing or painful gynecomastia.
Article
Mixed longitudinal data on the physical changes at puberty in 228 normal boys are presented together with normal standards for stages of genital and pubic hair development.The genitalia began to develop between the ages 9½ years and 13½ years in 95% of boys (mean = 11.6 ± 0.09) and reached maturity at ages varying between 13 and 17 (mean = 14.9 ± 1.10). The age at which pubic hair first appeared was not accurately determined, but its development through the later stages was studied. It reached the equivalent of an adult female distribution at a mean age of 15.2 ± 0.01 years.On average the genitalia reached the adult stage 3.0 years after they first began to develop; but some boys completed this development in as little as 1.8 years while others took as much as 4.7 years. Some boys complete the whole process in less time than others take to go from Stage G2 to Stage G3. The genitalia begin to develop before pubic hair is visible in photographs in practically all boys.The 41 boys in whom it could be studied reached their maximum rate of growth (peak height velocity) at a mean age of 14.1 ± 0.14 years.Very few boys (about 5%) reached peak height velocity before their genitalia were in Stage 4 and over 20% did not do so until their genitalia were adult. Peak height velocity is reached, on the average, nearly 2 years later in boys than in girls, but the boys' genitalia begin to develop only about 6 months later than the girls' breasts. Pubic hair appears about 1½ years later in boys than in girls.
Article
Single-agent therapy with bicalutamide, a nonsteroidal antiandrogen, was compared with castration, either surgical or medical, in patients with untreated Stage D2 prostate cancer. In an open, randomized, multicenter trial, patients were randomized to treatment with 50 mg bicalutamide (n = 243) once daily or to castration (n = 243), either orchiectomy or depot injection of goserelin acetate every 28 days. Primary efficacy endpoints were times to treatment failure and objective disease progression and survival. Assessments included review of measurable metastases, prostate dimensions, Eastern Cooperative Oncology Group performance status, pain, analgesic requirements, and quality of life responses. The median duration of therapy was 39 weeks for bicalutamide-treated patients and 42 weeks for castrated patients; treatment failure occurred in 53% and 42% and disease progression in 43% and 33%, respectively. Treatment effects favored castration for both endpoints (P < or = 0.002), with hazard ratios (bicalutamide:castration) of 1.54 (95% confidence interval [CI], 1.18 to 2.00) for time to treatment failure and 1.6 (95% CI, 1.19 to 2.15) for time to disease progression. From the 1-year survival analysis, the hazard ratio for probability of death was 1.29 (95% CI, 0.96 to 1.72). Thus far, with a median follow-up of 86 weeks, median survival has not been reached in either group. Changes from baseline in several quality of life variables were significantly different (P < or = 0.01) between treatment groups periodically from months 1 to 6, and all favored bicalutamide. Overall, the antiandrogen was well tolerated compared with castration; with bicalutamide, hot flushes occurred less often and breast tenderness and gynecomastia more often. Although a dosage of 50 mg of bicalutamide once daily was not as effective as castration, the favorable quality of life outcomes and the low incidence of nonhormonal adverse events provide reasons to evaluate bicalutamide, as a single therapeutic agent, at higher doses.
Article
17-Ketosteroid reductase deficiency results in male pseudohermaphroditism because conversion of the weak androgen androstenedione to the more potent androgen testosterone is impaired. If a late-onset form exists, hypogonadism and gynecomastia caused by decreased testosterone production and increased estrogen production, respectively, would be expected as the major clinical manifestations in men. We studied 48 male subjects, ranging from 14 to 26 years of age, who had idiopathic pubertal gynecomastia. Serum concentrations of gonadal and adrenal steroid hormones were measured before and after the administration of corticotropin and after the combined administration of chorionic gonadotropin and dexamethasone for three days. We identified three unrelated subjects (ages, 16, 17, and 26 years) with results indicative of a partial deficiency of testicular 17-ketosteroid reductase. The three subjects had gynecomastia as well as decreased libido and impotence. Their mean (+/- SD) base-line serum androstenedione and estrone concentrations were elevated as compared with the levels in the 45 subjects without this enzyme deficiency (androstenedione, 380 +/- 70 vs. 110 +/- 70 ng per deciliter [13 +/- 2 vs. 4 +/- 2 nmol per liter]; estrone, 138 +/- 12 vs. 46 +/- 9 pg per milliliter [511 +/- 44 vs. 170 +/- 33 pmol per liter]). After the administration of chorionic gonadotropin, the mean serum androstenedione concentration in these three subjects was 910 +/- 48 ng per deciliter (32 +/- 2 nmol per liter) and the mean serum estrone concentration was 260 +/- 16 pg per milliliter (962 +/- 59 pmol per liter). The mean serum testosterone concentration at base line was 210 +/- 80 ng per deciliter (7.4 +/- 2.8 nmol per liter) in the 3 subjects, as compared with a value of 410 +/- 12 ng per deciliter (14.4 +/- 0.42 nmol per liter) in the 45 other subjects, and it did not increase in response to the administration of chorionic gonadotropin. The concentrations of androstenedione and estrone in spermatic venous serum were 19 times higher and 73 times higher, respectively, than in normal men. The serum concentrations of follicle-stimulating hormone and luteinizing hormone in these three subjects were inappropriately low, suggesting the presence of hypogonadotropic hypogonadism. A late-onset form of testicular 17-ketosteroid reductase deficiency can cause gynecomastia and hypogonadism in men.
Article
Objectives: Bicalutamide is a new, potent antiandrogen with potential efficacy in the treatment of men with advanced prostate cancer. Although no pure antiandrogen has been well studied versus castration, potentially fewer adverse effects could occur, making such an agent a potentially useful alternative therapy. To date, three randomized controlled trials have been performed comparing these two treatments. In preliminary studies, a dose of 50 mg bicalutamide per day was selected for these trials. In two of the studies (0302, 0303), this drug was compared to either medical or surgical castration, the latter choice being made by the patient. In the third study (0301), bicalutamide was compared to bilateral orchiectomy. Methods: Using an intention-to-treat format, the outcomes assessed were time-to-treatment failure, time-to-objective disease progression, subjective response, and survival time in men with previously untreated metastatic disease. The incidence of breast tenderness, gynecomastia, and hot flushes was also determined in both treatment arms. A quality-of-life questionnaire was administered on multiple occasions after initiation of therapy. Results: Based on an analysis of > 1000 patients, the objective and subjective results favored castration over bicalutamide (50 mg/day). The hazard ratios for time-to-treatment failure (1.59), time-to-disease progression (1.62), and median survival (1.44) were all significantly greater in the castration group (P > 0.001). Another difference noted at 3 months was a significantly lower median fall in prostate-specific antigen values in the bicalutamide group (86-88% versus 96-97%). Symptomatic patients receiving bicalutamide were only 0.43 times as likely to have subjective improvement as the patients treated by castration. A comparison of pharmacologic effects showed that only the incidence of hot flushes was lower in the bicalutamide group, whereas breast tenderness and gynecomastia were more common. This difference in hot flushes, however, translated into better quality of life during the first several months with regard to sexual relations and sexual functioning. Conclusions: Bicalutamide monotherapy at 50 mg/day appears inferior to castration in overall objective and subjective response rates. Whether higher doses of bicalutamide can compete more favorably will need to be tested in further clinical trials.
Article
To compare the efficacy and tolerability of bicalutamide and flutamide, each combined with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with metastatic (Stage D2) prostate cancer. This was a randomized, double-blind (for antiandrogen therapy), multicenter study with a two-by-two factorial design. Eight hundred thirteen patients were allocated 1:1 to bicalutamide (50 mg once daily) and flutamide (250 mg three times daily) and 2:1 to goserelin acetate (3.6 mg every 28 days) and leuprolide acetate (7.5 mg every 28 days). The median times to progression and death were 97 and 180 weeks for the bicalutamide plus LHRH-A group compared with 77 and 148 weeks for the flutamide plus LHRH-A group. The hazard ratio for time to progression for bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.93 (95% confidence interval [CI] 0.79 to 1.10, P = 0.41) and that for survival time was 0.87 (95% CI 0.72 to 1.05, P = 0.15). The therapies were generally well tolerated. The most common adverse event in the two groups was hot flashes. The incidence of hematuria was significantly higher for the bicalutamide plus LHRH-A group than for the flutamide plus LHRH-A group (12% versus 6%, P = 0.007), but no patient withdrew from therapy because of hematuria. There was a significantly (26% versus 12%, P < 0.001) higher incidence of diarrhea and more withdrawals for diarrhea (25 patients versus 2) for the flutamide plus LHRH-A group relative to the bicalutamide plus LHRH-A group. With a median follow-up time of 160 weeks, the combination of bicalutamide plus LHRH-A was well tolerated and had equivalent time to progression and survival compared with flutamide plus LHRH-A. Treatment with bicalutamide plus LHRH-A resulted in longer median survival than treatment with flutamide plus LHRH-A.
Article
Current therapies for advanced prostate carcinoma lead to a marked decrease in serum testosterone levels, which renders patients impotent. In preliminary studies, combination therapy with flutamide and finasteride has been used as an alternative therapy for the treatment of prostate carcinoma because potency can be preserved. Both of these agents can cause gynecomastia and breast/nipple tenderness. Six men being treated for advanced prostate carcinoma with flutamide/finasteride combination therapy developed painful gynecomastia, which was treated with tamoxifen 10 to 30 mg/day for 1 month. Clinical follow-up included breast measurements and determination of prostate-specific antigen (PSA), testosterone, and estradiol levels. While on this combination therapy for prostate carcinoma, 4 of 6 patients experienced a decrease in PSA level to less than 0.5 ng/mL. All patients remained potent. Serum testosterone increased in each patient who had a baseline level drawn. Estradiol levels were noted to be elevated in 4 of 6 patients at the time of evaluation for gynecomastia. After treatment with tamoxifen, circulating estradiol levels increased in 3 patients from 1.3 to 2.2 times the baseline level. Five patients experienced complete resolution of breast and nipple pain on tamoxifen 10 mg/day within the first month. The other patient had to be treated with 30 mg/day for 1 additional month, which subsequently resulted in pain resolution. These preliminary results suggest that low-dose tamoxifen is useful in treating painful gynecomastia for those patients on flutamide/finasteride combination therapy for advanced prostate carcinoma.
Article
This prospective, randomized phase III study was initiated to compare the efficacy and side effects of bilateral orchiectomy versus a combination of a luteinizing hormone-releasing hormone agonist depot formulation, goserelin acetate (3.6 mg s.c. once every 4 weeks) and flutamide (250 mg 3 x daily) in patients with metastatic prostate cancer. Relative treatment efficacy was assessed by comparing the two treatment groups with respect to response, time to first progression, progression-free survival, duration of survival and time to death due to malignant disease. There was a difference in response only with respect to a more frequent decrease to normal of the serum prostate acid phosphatase in patients assigned to maximal androgen blockade treatment. Additionally, maximal androgen blockade treatment showed significantly better results for duration of survival (p = 0.04), time to death due to malignant disease (p = 0.008), time to first progression (p = 0.009) and progression-free survival (p = 0.02). The most frequent side effects for both treatments included hot flushes and gynaecomastia. Increased time to progression and duration of survival is achieved by the combination of flutamide and goserelin when compared to bilateral orchiectomy.
Article
Klinefelter syndrome is the most common sex chromosome disorder. Affected males carry an additional X chromosome, which results in male hypogonadism, androgen deficiency, and impaired spermatogenesis. Some patients may exhibit all of the classic signs of this disorder, including gynecomastia, small testes, sparse body hair, tallness, and infertility, whereas others, because of the wide variability in clinical expression, lack many of these features. Treatment consists of testosterone replacement therapy to correct the androgen deficiency and to provide patients with appropriate virilization. This therapy also has positive effects on mood and self-esteem and has been shown to protect against osteoporosis, although it will not reverse infertility. Although the diagnosis of Klinefelter syndrome is now made definitively using chromosomal karyotyping, revealing in most instances a 47,XXY genotype, the diagnosis also can be made using a careful history and results of a physical examination, with the hallmark being small, firm testes. As it affects 1 in 500 male patients and presents with a variety of clinical features, primary care physicians should be familiar with this condition.
Article
The objective of our study was to analyze factors determining diagnostic versus cosmetic indication and postoperative results in the treatment of gynecomastia. Data from 100 patients and 141 breasts were analyzed retrospectively, and reevaluated by questionnaire (n = 81) and clinical examination (n = 33). Except for 2 patients, all underwent subcutaneous mastectomy through various incisions. Diagnostic surgery was exclusively performed in unilateral, nodular gynecomastia being preferentially of grade I. Higher grade, bilateral gynecomastia led mainly to cosmetic surgery. Minor complications (skin retraction, hypertrophic scars, hypesthesia, skin redundancy) occurred in 53% of patients and significantly more often in grade III or II gynecomastia. Each incision was preferentially associated with specific sequelae. However, 86% of patients were satisfied with surgical results. Laterality, consistency, grade, and age at onset of symptoms determine surgical indication. Despite the high number of sequelae due to preoperative grade and selected incision, most patients are satisfied with postoperative results.
Article
Idiopathic gynecomastia, unilateral or bilateral, is a common physical finding in normal men. Successful treatment using tamoxifen (antiestrogen) and danazol (antiandrogen) has recently been reported. We compared the efficacy of tamoxifen and danazol in the treatment of idiopathic gynecomastia. We reviewed the clinical records of patients with idiopathic gynecomastia presenting to the Department of Surgery, University of Hong Kong, between August 1990 and September 1995. Medical treatment with either tamoxifen (20 mg/d) or danazol (400 mg/d) was offered and continued until a static response was achieved. The treatment response was compared. Sixty-eight patients with idiopathic gynecomastia were seen in the Breast Clinic. The median age was 39.5 years (range, 13-82), with a median duration of symptoms of 3 months (range, 1-90). The median size was 3 cm (range, 1-7). Twenty-three patients were treated with tamoxifen and 20 with danazol. Complete resolution of the gynecomastia was recorded in 18 patients (78.2%) treated with tamoxifen, whereas only 8 patients (40%) in the danazol group had complete resolution. Five patients, all from the tamoxifen group, developed recurrence of breast mass. In conclusion, hormonal manipulation is effective in the treatment of patients with idiopathic gynecomastia. Although the effect is more marked for tamoxifen compared with danazol, the relapse rate is higher for tamoxifen. Further prospective randomized studies would be useful in defining the role of these drugs in the management of patients with idiopathic gynecomastia.
Article
The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade. Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate). There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone. Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.
Article
Objectives: To compare the effect on overall survival of total androgen ablation (TAA) with that of parenteral estrogen and to pay special attention to cardiovascular mortality. TAA (orchiectomy or a luteinizing hormone-releasing hormone analogue combined with an antiandrogen) has been proposed as superior to other endocrine treatments for patients with prostate carcinoma. Recently, the use of parenteral estrogen has been suggested to reduce or even negate the well-known cardiovascular side effects of oral estrogens. Methods: Nine hundred fifteen patients were randomized to intramuscular injections of 240 mg polyestradiol phosphate (PEP) every second week for the first 8 weeks (5 doses) followed by a maintenance dose of 240 mg every month (n = 458) or to bilateral orchiectomy or triptorelin 3.75 mg every month combined with the antiandrogen flutamide 250 mg three times daily. The choice between orchiectomy and triptorelin was at the discretion of the clinician and patient. Patients were stratified according to performance status, presence of cardiovascular disease, and alkaline phosphatase level. An observer totally unaware of the treatment given classified all deceased patients. Results: At a median follow-up of 18.5 months, no signs of a difference in overall survival were found between TAA and PEP (P <0.001). Of 458 patients, 266 (58.1%) had died in the PEP group compared with 269 (58.9%) of 457 patients in the TAA group. Within the TAA group, no difference in overall survival existed between patients who had undergone orchiectomy or who were given triptorelin. Furthermore, no differences in cardiovascular mortality were found (3.5% in the PEP group and 3.1% in the TAA group). Conclusions: The current parenteral estrogen regimen seems to be of comparable efficacy and cardiovascular safety as TAA in terms of overall survival. PEP has by far the lowest drug cost and also the lowest cumulative direct costs and thus has the highest cost-effectiveness. We suggest that parenteral estrogen be included as a therapeutic option in the endocrine management of prostate carcinoma.
Article
Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide monotherapy or castration. Data from 2 open label, multicenter studies of identical design were pooled according to protocol. Patients with stage T3/4 prostate cancer were randomized to receive 150 mg. bicalutamide daily or castration (orchiectomy or 3.6 mg. goserelin acetate every 28 days) in a 2:1 ratio. A total of 480 patients with locally advanced prostate cancer were randomized to treatment. After a median followup of 6.3 years mortality was 56%. There was no statistically significant difference between the 2 groups in overall survival (hazard ratio 1.05, upper 1-sided 95% confidence limit 1.31, p = 0.70) or time to progression (1.20, 1.45, p = 0.11). There were statistically significant benefits in the bicalutamide monotherapy group in the 2 quality of life parameters of sexual interest (p = 0.029) and physical capacity (p = 0.046). The highest incidences of adverse events were the pharmacological side effects of hot flashes in the castration group, and breast pain and gynecomastia in the bicalutamide group. The incidences of other types of adverse events were low. Bicalutamide was well tolerated, with few drug related withdrawals from study, and no new safety issues were identified during this longer followup. Monotherapy with 150 mg. bicalutamide is an attractive alternative to castration in patients with locally advanced prostate cancer for whom immediate hormone therapy is indicated.
Article
To review the results of non-interventional observational cohort studies of 14 772 patients treated with finasteride and 12 484 patients treated with tamsulosin, both studies being of national proportions and undertaken in general medical practice in England. Both studies were undertaken by prescription-event monitoring (PEM), whereby the exposure data are derived from information provided in strict confidence by the Prescription Pricing Authority of the National Health Service. The outcome data are derived from 'green form' questionnaires completed by the prescribing general practitioners (GPs). Additional data are obtained by medical follow-up with the attending practitioners. Adverse experience was measured in three ways; as reports of events which the doctors considered to represent adverse drug reactions; as reports of reasons for stopping the drug; and by studying the incidence density of each reported event. For these purposes a computerized dictionary containing 1430 higher level terms was used. The duration of exposure in the finasteride study was approximately 1 year and was approximately 6 months in the tamsulosin study. The outcome data on the 14 772 and 12 484 patients treated in the finasteride and tamsulosin studies were derived from the 63% and 57.4% of the green forms sent out and returned, respectively. The finasteride cohort included two women and the tamsulosin cohort 70 women. The mean (SD) age of the men in the two cohorts was, respectively, 69.0 (9.2) and 66.2 (11.7) years. Both drugs were well tolerated on long-term therapy and 69.6% (10 274 patients) of the total finasteride and 62.0% (7739 patients) of the total tamsulosin cohort were still receiving the drug at the end of 6 months. In the finasteride study, impotence or ejaculatory failure was reported in 2.0% of the patients still receiving the drug; there were reports of decreased libido in 1.0% and gynaecomastia was reported whilst the drug was still being prescribed in 39 patients (0.3% of the cohort). With tamsulosin, uncommon cases of dizziness, headache, malaise and hypotension (89 reports in 12 484 patients, i.e. 0.7% of the cohort) were common to the findings of reported adverse reactions, reasons for stopping the drug and events of highest incidence density. None of the deaths which occurred in either of these large cohorts was attributed by either the reporting GPs or the PEM medical staff to the drugs examined. Conclusion The GPs rated the drugs effective in most patients; tolerance and adverse experience was consistent with the known pharmacology of the two drugs. No serious, unexpected adverse effects were identified.
Article
To investigate the efficacy and tolerability of bicalutamide (Casodex) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with localized or locally advanced (T1b-T4, any nodal status, M0) prostate cancer. This was a multicenter, prospective, randomized, double-blind, placebo-controlled trial in Europe, South Africa, Australia, and Mexico and is part of the Casodex Early Prostate Cancer program. A total of 3603 men were randomized to receive bicalutamide (n = 1798) or placebo (n = 1805). The patient demographics were well balanced between the two groups. Prior therapy of curative intent had been given to 64% of the patients (prostatectomy [44%], radiotherapy [18%], and prostatectomy and radiotherapy [2%]) and 36% had been monitored with watchful waiting. After a median follow-up of 2.6 years and a median exposure to the study drug of 2.2 years, a significant 43% reduction in the risk of objective progression was observed for the bicalutamide group compared with the placebo group (hazard ratio 0.57, 95% confidence interval 0.48 to 0.69, P < 0.0001). The time to prostate-specific antigen doubling was significantly delayed for the bicalutamide group compared with the placebo group (hazard ratio 0.37, 95% confidence interval 0.32 to 0.43, P < 0.001). The survival data were immature, with 7.2% overall mortality. The most frequently reported adverse events with bicalutamide were gynecomastia alone (17.4%), breast pain alone (17.6%), and gynecomastia with breast pain (47.5%). Bicalutamide 150 mg daily as immediate therapy, alone or as adjuvant to treatment of curative intent, significantly reduced the risk of disease progression in patients with localized or locally advanced prostate cancer. Longer follow-up is underway to assess any benefit in overall survival.
Article
To compare health-related quality-of-life outcomes after primary androgen deprivation (AD) therapy with orchiectomy versus luteinizing hormone-releasing hormone (LHRH) agonists for patients with prostate cancer. Men (n = 431) newly diagnosed with all stages of prostate cancer from six geographic regions who participated in the Prostate Cancer Outcomes Study and who received primary AD therapy but no other treatments within 12 months of initial diagnosis were included in a study of health outcomes. Comparisons were statistically adjusted for patient sociodemographic and clinical characteristics, timing of therapy, and use of combined androgen blockade. More than half of the patients receiving primary AD therapy had been initially diagnosed with clinically localized prostate cancer. Among these patients, almost two thirds were at high risk of progression on the basis of prognostic factors. Sexual function outcomes were similar by treatment group both before and after implementation of AD therapy. LHRH patients reported more breast swelling than did orchiectomy patients (24.9% v 9.7%, P <.01). LHRH patients reported more physical discomfort and worry because of cancer or its treatment than did orchiectomy patients. LHRH patients assessed their overall health as fair or poor more frequently than did orchiectomy patients (35.4% v 28.1%, P =.01) and also were less likely to consider themselves free of prostate cancer after treatment. Most endocrine-related health outcomes are similar after surgical versus medical primary hormonal therapy. Stage at diagnosis had little effect on outcomes. These results provide representative information comparing surgical and medical AD therapy that may be used by physicians and patients to inform treatment decisions.
Article
We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer. This international program consists of 3 ongoing, randomized, double-blind, placebo controlled clinical trials (trials 23, 24, and 25). Men with localized or locally advanced (T1-T4, Nx/N0, M0) prostate cancer were randomized to receive 150 mg. bicalutamide daily or placebo, in addition to standard care with radical prostatectomy, radiotherapy or watchful waiting. Primary end points are time to objective progression and overall survival. In this first analysis data from the trials were combined in a single overview analysis according to protocol. Data are available for 8,113 patients (4,052 randomized to bicalutamide, 4,061 to standard care alone) at a median followup of 3.0 years. Treatment with bicalutamide provided a highly significant reduction of 42% in the risk of objective progression compared with standard care alone (9.0% versus 13.8%, hazards ratio 0.58; 95% confidence interval 0.51, 0.66; p <0.0001). The overall result was reflected in 2 of the 3 trials (trials 24 and 25) with trial 3 (trial 23) showing a nonsignificant difference at this time. Reductions in the risk of disease progression were seen across the entire patient population, irrespective of primary treatment or disease stage. Overall survival data are currently immature and longer followup will determine if there is also a survival benefit with bicalutamide. The most frequently reported side effects of bicalutamide were gynecomastia and breast pain. Immediate treatment with 150 mg. bicalutamide daily, either alone or as adjuvant to treatment of curative intent, significantly reduces the risk of disease progression in patients with localized or locally advanced prostate cancer. This benefit must be balanced with the morbidity associated with long-term hormonal therapy. Followup is ongoing to determine potential survival benefits of this treatment approach.
Article
Prostatic carcinoma and its treatment have been associated with adverse effects on health-related quality of life (HRQoL). Individual differences in appraisal and coping have been suggested to mediate these HRQoL outcomes. A randomized trial of 65 men with non-localized prostate cancer compared several treatments and tested associations between appraisal, coping, and HRQoL. These patients, and 16 community volunteers matched for age and general health, undertook psychosocial assessments before treatment and after 6 months of treatment. Compared with baseline assessments, men on hormonal treatments reported impaired sexual function. Groups did not differ on emotional distress, existential satisfaction, subjective cognitive function, physical symptoms, or social and role functioning. For individuals, hormonal treatments were more frequently associated with decreased sexual, social and role functioning, but were also associated with improved physical symptoms. In hierarchical regression analysis, HRQoL was lower for men who had more comorbid illnesses, a history of neurological dysfunction, higher threat appraisals, or higher use of coping strategies at baseline. These results showed that pharmacological hormonal ablation for prostate cancer can improve or decrease HRQoL in different domains. HRQoL in men with prostate cancer was associated more strongly with appraisal and coping than with medical variables.
Article
To examine the development of antiandrogen-induced gynecomastia and breast tenderness in the first 253 patients in a randomized Scandinavian trial (SPCG-7/SFUO-3) with a 12-month complete follow-up evaluation performed by both doctors and patients. In this study, the treating doctor and patient decided whether prophylactic irradiation (RT) of the breast should be given to prevent antiandrogen-induced gynecomastia. At each visit, the doctor evaluated the occurrence of gynecomastia and breast tenderness. Questions about gynecomastia and breast tenderness were also included in the study quality-of-life questionnaire (Prostate Cancer Symptom Scale). Mammary RT with mostly single fraction (12 to 15 Gy) electrons was given to 174 (69%) of the 253 evaluated patients. At the 1-year follow-up visit, the doctor evaluations indicated some form of gynecomastia in 71% and 28% (P <0.001) of the nonirradiated (no-RT) and irradiated (RT) patients, respectively. The patient evaluations at 1 year showed some form of breast enlargement in 78% and 44% (P <0.001) of the no-RT and RT patients, respectively. The doctors reported some form of breast tenderness at 1 year in 75% and 43% (P <0.001) of the no-RT and RT patients, respectively. The patient evaluations of breast tenderness show an expected significant increase in the RT arm at the 3-month follow-up, which was probably due to skin reactions. At 1 year, significantly more patients who marked "very much" on the Prostate Cancer Symptom Scale were seen in the no-RT group. A weak correlation between the doctors' and patients' detection of breast problems was observed. The results show that, with high significance, prophylactic RT of the breast decreases the risk of antiandrogen-induced gynecomastia and breast tenderness.
Article
Gynecomastia, or excessive male breast development, has an incidence of 32 to 65 percent in the male population. This condition has important physical and psychological impacts. Advances in elucidating the pathophysiology of gynecomastia have been made, though understanding remains limited. Recommendations for evaluation and workup have varied and are often arbitrary. A diagnostic algorithm is suggested, with emphasis on a comprehensive history, physical examination, and minimizing unnecessary diagnostic testing. Medical management has had limited success; surgical therapy, primarily through excisional techniques, has been the accepted standard. Although effective, excisional techniques subject patients to large, visible scars. Ultrasound-assisted liposuction has recently emerged as a safe and effective method for the treatment of gynecomastia. It is particularly efficient in the removal of the dense, fibrous male breast tissue while offering advantages in minimal external scarring. A new system of classification and graduated treatment is proposed, based on glandular versus fibrous hypertrophy and degree of breast ptosis (skin excess). The authors' series of 61 patients with gynecomastia from 1987 to 2000 at the University of Texas Southwestern Department of Plastic Surgery demonstrated an overall success rate of 86.9 percent using suction-assisted lipectomy (1987 to 1997) and ultrasound-assisted liposuction (1997 to 2000). The authors have found ultrasound-assisted liposuction to be effective in treating most grades of gynecomastia. Excisional techniques are reserved for severe gynecomastia with significant skin excess after attempted ultrasound-assisted liposuction.
Article
Numerous techniques have been described for the correction of gynaecomastia, and the surgeon is faced with a wide range of excisional and liposuction procedures. There is a paucity of literature describing an integrated approach to the management of this condition and the roles of the different treatment modalities. A review of all gynaecomastia patients operated on by one surgeon over a 2-year period was undertaken. Patient satisfaction was assessed using a linear analogue scale with a maximum score of 10. In total, 48 breasts in 29 patients were treated--31 breasts by liposuction alone (19 by conventional liposuction, 12 by ultrasound-assisted liposuction), eight breasts by liposuction and open excision, and nine breasts by liposuction, open excision and skin reduction (concentric or Lejour mastopexy). There were no early postoperative complications, such as haematoma, seroma or infection, and 91% of patients were very satisfied (score: 8-10) with their cosmetic outcome. The most frequently encountered complication was a residual subareolar lump (five breasts), all in patients treated by conventional liposuction alone. In order to avoid the common complication of an uncomfortable residual subareolar nodule, the threshold for open excision in patients undergoing conventional liposuction should be low. Ultrasound-assisted liposuction extends the role of liposuction in gynaecomastia patients. Although skin excess remains a challenge, it can be satisfactorily managed without excessive scarring. A practical approach to the surgical management of gynaecomastia, which takes into account breast size, consistency, skin excess and skin quality, is proposed.
Article
To evaluate the impact of androgen deprivation on health related quality of life (HRQOL) in patients with asymptomatic lymph node positive prostatic carcinoma (LPPC). HRQOL domains were measured, using standard instruments in 91 patients with histologically proven LPPC. Most patients were randomized for immediate or deferred hormonal treatment until progression was observed. For analyses concerning the time to progression and survival the Kaplan-Meier method was used. Patients treated with androgen deprivation showed a significantly worse sexual, emotional, and physical function, experienced more hot flushes and a worse overall HRQOL, compared with patients receiving no therapy. Time to progression was significantly shorter in the deferred treated patients in comparison with the immediately treated patients (33 vs. 62 months, p<0.001). No significant differences were found with respect to the duration of survival. Hormonally treated patients with asymptomatic LPPC have a worse HRQOL compared with patients receiving no therapy. The duration of survival was similar, whether patients received immediate or deferred hormonal treatment. Nowadays, with patients' preferences playing an increasingly important role in therapeutic decision making, physicians should be aware of this negative impact and ought to inform the patients on this.
Article
The last 30 years has seen a shift in surgical treatment of breast diseases to less invasive, more conservative treatment options. The mammotome equipment was originally introduced as a diagnostic tool, but advances in technology have extended its role to therapeutic procedures. The mammotome device (8-gauge) is inserted through a cosmetically placed 4-mm scar and breast tissue is resected sequentially using a suction facility without the need to remove the biopsy device. This is done under ultrasound guidance. Operative morbidity and postoperative score for cosmesis and patient satisfaction were recorded prospectively. Patients were reviewed in the clinic after 6 to 8 weeks. Five patients (4 unilateral, 1 bilateral) with idiopathic gynecomastia were treated. Mean age was 41.8 years (range, 16-88 years) with a median procedural time of 32 minutes. No postoperative morbidity was noted and mean cosmetic score was 9/10. The mammotome is an emerging minimal invasive tool that is safe and ensures excellent cosmesis and very high patient satisfaction rates.
Article
Pubertal gynecomastia is thought to result from transient imbalances between estrogen and androgen concentrations. Anastrozole (ARIMIDEX), a potent and selective aromatase inhibitor, decreases estrogen and increases testosterone concentrations in pubertal boys. The safety and efficacy of anastrozole for the treatment of pubertal gynecomastia were evaluated. In a randomized, double-blind, placebo-controlled study of 80 boys, aged 11-18 yr, with pubertal gynecomastia that had not reduced over a 3-month interval, subjects received either anastrozole (1 mg) or placebo once daily for 6 months. A response was defined as a 50% or greater reduction in the calculated volume of both breasts combined using ultrasonography measurements. A comparison of response rates was performed using logistic regression analysis. Secondary end points included changes in serum hormone concentrations. The percentage of patients with a response was 38.5% for the anastrozole group and 31.4% for the placebo group (odds ratio, 1.513; 95% confidence interval, 0.496-4.844; P = 0.47). At 6 months, the median percent change in the testosterone/estradiol ratio was 166% for the anastrozole group and 39% for the placebo group. Anastrozole treatment was well tolerated. In patients with pubertal gynecomastia, no significant difference in the percentage of patients with a 50% or greater reduction in total breast volume, as calculated from ultrasonography measurements, was demonstrated between the anastrozole and placebo groups.
Article
To evaluate the efficacy and tolerability of prophylactic breast irradiation in reducing the incidence and severity of bicalutamide-induced gynecomastia and breast pain. In all, 106 men with prostate cancer (T1b-T4/Nx/M0) and no current gynecomastia/breast pain were enrolled in this randomized, sham-controlled, double-blind, parallel-group multicenter trial. Patients received either a single dose of electron beam radiotherapy (10 Gy) or sham radiotherapy. Bicalutamide (Casodex) 150 mg/day was administered for 12 months from the day of radiotherapy. Every 3 months, patients underwent physical examination and questioning about gynecomastia and breast pain. The incidence of investigator-assessed gynecomastia was significantly lower with radiotherapy vs. sham radiotherapy (52% vs. 85%; odds ratio [OR], 0.13; 95% confidence interval [CI], 0.04, 0.38; p < 0.001); direct questioning showed similar results. Fewer radiotherapy patients had >/=5 cm gynecomastia (measured by calipers; 11.5% vs. 50.0% for sham radiotherapy), and fewer cases were moderate-to-severe in intensity (21% vs. 48%). Similar proportions of radiotherapy and sham radiotherapy patients experienced breast pain (83% vs. 91%; OR, 0.25; 95% CI, 0.05, 1.27; p = 0.221); patients receiving radiotherapy experienced some reduction in its severity (OR, 0.44; 95% CI, 0.20, 0.97; p = 0.0429). Prophylactic breast irradiation is an effective and well-tolerated strategy for prevention of bicalutamide-induced gynecomastia.
Ultra-sound guided minimally invasive breast surgery (UMIBS): a superior technique for gynecomastia Surgical treat-ment of gynecomastia: liposuction combined with subcutane-ous mastectomy
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Iwuagwu, O. C., Calvey, T. A., Ilsley, D. and Drew, P. J.: Ultra-sound guided minimally invasive breast surgery (UMIBS): a superior technique for gynecomastia. Ann Plast Surg, 52: 131, 2004 23. Boljanovic, S., Axelsson, C. K. and Elberg, J. J.: Surgical treat-ment of gynecomastia: liposuction combined with subcutane-ous mastectomy. Scand J Surg, 92: 160, 2003
Comparison of tamox-ifen with danazol in the management of idiopathic gynecom-astia Tamoxifen (T) is more effective than Anas-trozole (A) in preventing gynecomastia induced by Bicaluta-mide (B) monotherapy in prostate cancer
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Ting, A. C., Chow, L. W. and Leung, Y. F.: Comparison of tamox-ifen with danazol in the management of idiopathic gynecom-astia. Am Surg, 66: 38, 2000 33. Boccardo, F., Rubagotti, A., Garofalo, L., Di Tonno, P., Conti, G., Bertaccini, A. et al: Tamoxifen (T) is more effective than Anas-trozole (A) in preventing gynecomastia induced by Bicaluta-mide (B) monotherapy in prostate cancer (pca) patients (pts).
Aromatase and gynecomastia. Endocr Relat Cancer
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Klinefelter syndrome Arch Intern Med
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Tamoxifen (T) is more effective than Anastrozole (A) in preventing gynecomastia induced by Bicalutamide (B) monotherapy in prostate cancer (pca) patients (pts)
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