Painful Gynaecomastia Research Articles

Managing Male Mammary Maladies.

This review examines the symptoms, need for referral and management of the benign breast conditions which afflict males, together with the steps that are necessary to exclude or confirm male breast cancer. The most common complaint is gynaecomastia, either true or pseudo, and the majority of these cases need reassurance without over-investigation. Drugs that induce breast enlargement are described in order that, when possible, a medication switch can be made. Men receiving endocrine therapy for prostate cancer may develop painful gynaecomastia and this can be relieved with tamoxifen. All men with breast cancer need mammography as part of their work-up but this should not be used as a screening technique for symptomatic males. Because of lack of lobular development, both cysts and fibroadenomas are very rare in men; but those with nipple discharge need referral and investigation as some will have underlying malignancy.

Hypogonadism in an opioid dependent man.

We describe here the case of a 45-year-old man with a chronic history of heroin abuse who has received methadone maintenance therapy for 12 years. At admission, on this occasion, for stabilisation on methadone, he reported a two-year history of painful gynaecomastia and testicular atrophy. Investigations revealed abnormal sex hormone levels. Liver function tests, thyroid function tests, Brain (pituitary) MRI and viral screens were normal. Following assessment and abnormality in two morning total testosterone level measurements he was diagnosed with hypogonadism secondary to opioid use. Although he had a previous history of alcohol abuse, he was abstinent from alcohol use for five years at time of assessment. He was commenced on parenteral testosterone replacement with therapeutic benefit. In light of the increased use of opioids, it is important to recognise and manage the endocrine complications of opioid use. The need for an empathic and adequate sexual history, physical examination and investigation is essential in patients who use opioids to ensure that cases of hormonal dysfunction are detected early and managed appropriately.

A multi-centre randomised phase III trial of Dexamethasone vs Dexamethasone and diethylstilbestrol in castration-resistant prostate cancer: immediate vs deferred Diethylstilbestrol

Background:The role of further hormone therapy in castration-resistant prostate cancer (CRPC) remains unclear. We performed a multi-centre randomised phase III study comparing the use of Dexamethasone, Aspirin, and immediate addition of Diethylstilbestrol (DAiS) vs Dexamethasone, Aspirin, and deferred (until disease progression) addition of Diethylstilbestrol (DAdS).Methods:From 2001 to 2008, 270 men with chemotherapy-naive CRPC were randomly assigned, in a 1 : 1 ratio, to receive either DAiS or DAdS. They were stratified for performance status, presence of bone metastases, and previous normalisation of prostate-specific antigen (PSA) to androgen deprivation. The study end points were the proportion of patients achieving a 50% PSA response, progression-free survival (PFS), overall survival, and quality of life. Intention-to-treat analysis was carried out. The effect of treatment was studied first by Kaplan–Meier curves and log-rank test, and finally through multivariable stratified Cox's proportional hazards model adjusting for the effects of possible baseline prognostic factors. Quality of life was analysed using multivariate analysis of variance.Results:At study entry, the median age was 76 years (inter-quartile range: 70–80 years), the median PSA was 79 ng ml−1, and 76% of the cohort had metastatic disease. The response rates for DAiS (68%) and DAdS (64%) were not significantly different (P=0.49). Similar to the response rate, neither the PFS (median=8.1 months for both arms) nor the overall survival (19.4 vs 18.8 months) differed significantly between the DAiS and DAdS groups (P>0.20). However, the response rate for the DAiS (68%) was significantly higher than the response rate of DA (before adding Diethylstilbestrol) (50%) (P=0.002). Similarly, the median time to progression for DAiS (8.6 months) was significantly longer than that of DA (4.5 months) (P<0.001). Multivariable analysis showed that patients with previous haemoglobin ⩾11 g dl−1 decreased the risk of death significantly (hazard ratio: 0.44, 95% CI: 0.25–0.77). Patients treated with previous anti-androgens alone had more than 5 times more risk of death compared with patients treated with gonadorelin analogues throughout their castration-sensitive phase. Treatment sequencing did not affect the quality of life but pre-treatment performance status did. The incidence of veno–thromboembolic events was 22% (n=28) in DAiS and 11% (n=14) in the DA arm (P=0.02). Painful gynaecomastia occurred in only 1% on DA, whereas in 40% on DAiS (P=0.001).Conclusion:Dexamethasone and immediate Diethylstilbestrol resulted in neither higher PSA response rate nor higher PFS compared with Dexamethasone with deferred Diethylstilbestrol. There was no suggestion of significantly improved overall survival or quality of life. Given the significantly higher toxicity of Diethylstilbestrol, deferring Diethylstilbestrol until failure of Dexamethasone is the preferred strategy when using these agents in CRPC.

Eplerenone reverses spironolactone-induced painful gynaecomastia in cirrhotics

To investigate the efficacy and safety of aldosterone antagonist, eplerenone in the treatment of spironolactone-induced painful gynaecomastia in cirrhotic patients. A number of 19 consecutive patients with cirrhosis due to alcohol abuse or chronic hepatitis B, who had been administered spironolactone and suffered from painful gynaecomastia, have been included in the study. Substitution of spironolactone with eplerenone was followed for 3months under close inspection. Age and gender, along with Child-Pugh stage of cirrhosis, pain (in a 1-5 visual analogue scale), Na(+), K(+), FSH, LH, 17 (OH) progesterone, DHEA-S, testosterone, and prolactin were measured at the beginning and the end of the study. All 19 patients expressed alleviation of pain (P<0.001). Two patients deteriorated and two other ameliorated as far as the Child-Pugh score is referred. All biochemical and hormonal parameters remained unchanged. In cirrhotic patients with painful gynaecomastia, the use of eplerenone instead of spironolactone might reverse pain and seems to be safe and clinically acceptable option.

Where are my testes?

In October, 2007, a 42-year-old man presented to us with pleuritic chest pain similar to his previous presentations of recurrent pulmonary emboli (PE). He was poorly compliant to warfarin prescribed for a diagnosis of heterozygous factor V Leiden deficiency 3 years previously. The most recent PE (July, 2006) was from self-cessation of warfarin a year ago for a period of 4 months. On examination he had bilateral painful gynaecomastia. On detailed questioning, he reported reduced libido and relationship problems which had evolved over the past year.

Testosterone and estradiol levels in male gynecomastia. Clinical and endocrine findings during treatment with tamoxifen

Oestradiol-(E2) levels in serum were significantly higher in a group of 91 males with gynaecomastia than in a control group. The levels were highest in patients with testicular tumour, hyperprolactinaemia and idiopathic gynaecomastia. In gynaecomastia of puberty and primary or secondary hypogonadism, the E2 level was within normal limits, but the testosterone/oestradiol ratio was significantly reduced. Tamoxifen, at a daily dose of 20 mg, was administered over 2-4 months to 16 patients with gynaecomastia. Of twelve patients with painful gynaecomastia ten became painfree. Gynaecomastia regressed partially or completely in 14 patients, in only 2 was it unchanged. There was no recurrence of gynaecomastia after discontinuing tamoxifen. Side-effects did not occur. It is concluded that tamoxifen is a promising alternative to the surgical treatment of gynaecomastia.

Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism

The aim of this prospective, randomised, open-label, blinded-end point study was to compare the efficacy and safety of eplerenone versus spironolactone in patients with bilateral idiopathic hyperaldosteronism (IHA). After a 2-week washout period, 34 patients with IHA were assigned to receive either spironolactone 25 mg b.i.d. (n = 17) or eplerenone 25 mg b.i.d. (n = 17) for 24 weeks. If the patients' blood pressure (BP) was not < 140/90 mmHg, the doses were gradually increased up to 400 mg for spironolactone and 200 mg for eplerenone. If the patients' BP remained uncontrolled, a daily dose of hydrochlorothiazide 12.5 mg was added at week 16. The primary outcome was the percentage of patients with BP < 140/90 mmHg at 16 weeks (i.e., with aldosterone antagonist monotherapy). The patients' BP was normalised in 13 out of 17 (76.5%) and 14 out of 17 (82.4%) patients in the spironolactone and eplerenone groups, respectively (p = 1.00). Systolic BP decreased more rapidly with eplerenone. Serum potassium levels were normalised (> 3.5 mmol/l) in all patients at 4 weeks. Mild hyperkalaemia was observed in two patients receiving 400 mg of spironolactone and in three patients receiving 150 mg of eplerenone. Two patients presented with bilateral painful gynaecomastia at the end of week 16 while receiving 400 mg of spironolactone. Switching spironolactone to 150 mg of eplerenone daily resulted in resolution of gynaecomastia and also maintained BP control. At the end of the study, 19 patients were on eplerenone and 15 were on spironolactone. However, this did not affect the primary end point, because the switch from spironolactone to eplerenone (in two patients) occurred at the end of week 16. It was concluded that eplerenone was as effective as spironolactone in reducing BP in patients with IHA. The risk of mild hyperkalaemia was similar with both drugs.

Human chorionic gonadotropin-secreting clear cell renal cell carcinoma with paraneoplastic gynaecomastia

A 60-year-man presented with painful gynaecomastia and polycythaemia due to a beta-human chorionic gonadotropin (HCG)-secreting clear cell renal cell carcinoma. A computed tomographic scan of his chest, abdomen and pelvis showed an enhancing 9x9 cm mass in the right kidney suggestive of a renal cell carcinoma. He underwent right radical nephrectomy and the histology showed a clear cell renal cell carcinoma. Following his nephrectomy, over the next 6 months, his gynaecomastia regressed and serum beta-HCG levels became undetectable. Nine months after his nephrectomy, he developed a paratesticular lesion involving scrotal skin, for which he underwent a right radical orchidectomy. Histopathology of the paratesticular lesion showed metastatic renal cell carcinoma.

Eplerenone relieves spironolactone-induced painful gynaecomastia in a patient with primary aldosteronism

Sir, Eplerenone is the second oral aldosterone antagonist available for the treatment of essential hypertension and congestive heart failure. Spironolactone, the first aldosterone antagonist, although effective for the above conditions, has progestational and antiandrogenic adverse effects due to its non-specific binding to various steroid receptors. We report the case of a 54-year-old Caucasian man, who was admitted to hospital because of severe hypertension and hypokalaemia. The plasma aldosterone/plasma renin activity ratio was well above the cut-off level of 30 ng/dl/ng ml � 1 h � 1 . The acute intravascular volume expansion with the intravenous administration of isotonic saline showed autonomous aldosterone production. The aforementioned results were considered diagnostic of primary aldosteronism. A computerized tomography scan with fine cuts (2.5–3 mm) showed bilateral adrenal gland hyperplasia. Therefore, the patient was started on spironolactone 100 mg t.d.s., and in the following days normokalaemia was restored and blood pressure was well-controlled. Two months later, the patient presented with bilateral painful gynaecomastia. We switched spironolactone to eplerenone 25 mg t.d.s., and the patient was completely relieved within 1 month, while his blood pressure remained well-controlled and serum potassium was normal. Spironolactone is the drug of choice for the treatment of primary aldosteronism, but presents sexual side effects, such as impotence, painful gynaecomastia and menstrual disturbances in pre-menopausal women. Several mechanisms have been proposed for these side effects, such as a dosedependent reduction of microsomal cytochrome P-450, alterations of the testosterone–estrogen ratio, a fall in plasma testosterone or a significant increase in its metabolic clearance, and the peripheral conversion of testosterone to estradiol or increased serum levels of estrone and estradiol [1]. Gynaecomastia may be quite remarkable and its occurrence is dose- and time-dependent. Eplerenone is a highly selective aldosterone antagonist. Spironolactone is approximately 40-fold more potent than eplerenone in blocking aldosterone activation of mineralocorticoid receptor. However, the selectivity of eplerenone is significantly greater than spironolactone at androgen, progesterone and glucocorticoid receptors. Eplerenone is 370-fold less potent at blocking dihydrotestosteroneactivation of androgen receptors compared with spironolactone [2]. Two large clinical studies have evaluated the efficacy and tolerability of these aldosterone antagonists. The Randomized Aldactone Evaluation Study (RALES) found that the administration of spironolactone 12.5–50 mg/day,

The role of tamoxifen in the management of gynaecomastia

Gynaecomastia affects half of the male population at some stage in their life. Only a small proportion of them would require treatment for cosmetic appearance or to relieve pain and tenderness. Recently, tamoxifen has shown some promising results in the management of gynaecomastia. To assess the efficacy of tamoxifen, we carried out a retrospective study of all men treated for gynaecomastia with particular emphasis on those treated medically. Men with painful gynaecomastia were given 10 mg of tamoxifen for 3 months. Response to treatment was categorised as good, moderate and no response. Thirteen men (median age 36) were placed on tamoxifen. Ten patients responded well to tamoxifen. One patient developed calf tenderness and stopped the medication. No other adverse effects were reported. Two patients could not be followed up. Tamoxifen appears safe and effective in men with painful idiopathic or physiological gynaecomastia and should be considered as an initial option before contemplating surgery.

Occult Leydig Cell Tumour Presenting as Bilateral Gynaecomastia. Case Report and Literature Review

Gynaecomastia is the most common benign breast disorder in men. Among the various causes, testicular malignancies are an uncommon, life-threatening condition requiring prompt diagnosis and treatment. The case of a 28-year-old man is discussed, who presented with a 6-month history of painful bilateral gynaecomastia with no abnormality on clinical or biochemical examination. The patient's symptoms spontaneously resolved within 4 weeks. He then represented 10 years later with similar symptoms and an associated secondary hypogonadism. Ultrasound imaging revealed a clinically occult, hypoechoic mass in the left testis (Leydig cell tumour on histology). Clinical and hormonal findings normalized following surgical excision. This report underlines the importance in clinical practice of ultrasonographic evaluation of the testis, in all patients with gynaecomastia, despite unremarkable findings on physical examination.

Danazol in the treatment of gynaecomastia.

Gynaecomastia develops in association with a variety of underlying factors. Many cases are mild in degree and of short duration and do not require treatment. However, quite severe and painful gynaecomastia can occur. In such cases treatment with danazol can lead to a marked reduction in size and a lessening of pain and tenderness of the breasts. In 60 % of all patients a marked reduction of gynaecomastia can be expected and in a further 24 % a moderate reduction. Variable degrees of response occur in relation to the underlying aetiological cause. Therapy is associated with a demonstrable fall in the plasma concentrations of follicle stimulating hormone (FSH) and luteinising hormone (LH) with a decreased urinary excretion of FSH and LH in most patients studied. A significant fall in plasma testosterone occurs in the majority of patients. Estimations of thyroidal and adrenal function show no change. Dosage schedules in adults range from 300 to 600mg a day and in adolescents from 200 to 300mg a day. Side effects of therapy relate mostly to the androgenic properties of danazol which may result in weight gain with fluid retention and acne. Muscle weakness and muscle cramps and spasms occur in a small percentage of patients.