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Therapeutics Today
January 2017
Number 1
For personal use only. Not to be reproduced without permission of the NMIC.
All you need to know about gynaecomastia. Gynaecomastia (GM),
which describes the benign proliferation of glandular breast tissue, occurs in 35% of men
and is most prevalent between the ages of 50 and 69 years (BMJ 2016;354:i4833). It is
characterised by the presence of a palpable, firm, subareolar gland and ductal tissue
(not fat) resulting in breast enlargement. GM occurs as a result of a hormone imbalance,
either an excess of oestrogens/oestrogen precursors or a reduction/impairment of
androgens. The cause of the hormone imbalance may be due to physiological, drugrelated or disease causes; GM is strongly correlated with obesity, which is known to cause increased peripheral
aromatisation of oestrogen precursors. Physiological GM is often seen in neonates (affects up to 90% of
newborns; it usually resolves spontaneously within a few weeks), at puberty (affects up to 60% of adolescents at a
mean age of 12-14 years; it spontaneously resolves in 90% within 6-12 months) and in older men (occurs in 65%
of men >65 years; it is thought to be due to decreasing testosterone levels however investigation is required if the
history is suggestive of pathological cause). Drug-induced GM is an important cause of GM and a detailed review
of medication is required. Drugs known to cause GM include antiandrogens (bicalutamide, finasteride,
dutasteride), antihypertensives (spironolactone, calcium channel blockers), antiretrovirals (protease inhibitors,
reverse transcriptase inhibitors), exogenous hormones (oestrogens, prednisone, androgens), gastrointestinal
drugs (cimetidine, proton pump inhibitors), analgesics (opioids), antifungals (ketoconazole), antipsychotics
(haloperidol, olanzapine, paliperidone, risperidone) and some chemotherapy drugs (methotrexate, alkylating
agents). Some other drugs may rarely cause GM including amiodarone, aripiprazole, atorvastatin, captopril,
cetirizine and clonidine. The use of illicit drugs and body building supplements should also be explored with
younger men as these may also be associated with GM. Intake of high levels of alcohol long-term causes
increased aromatase activity and increased adrenal production of oestrogen precursors. Pathological causes of
GM include gonadal failure (causes of primary failure include chromosomal [Klinefelter’s syndrome], trauma,
chemotherapy and inflammatory damage while those of secondary failure include pituitary adenoma),
hyperthyroidism, liver cirrhosis, renal insufficiency and hormone secreting tumours (testicular tumours [present in
3% of men with GM], adrenocortical tumours). Many men with GM are asymptomatic and unaware of their excess
breast tissue.
The diagnosis of GM is clinical. Patients present with a history of slow breast enlargement which may be
unilateral or bilateral; common symptoms include breast tenderness and pain around the nipple area. The Simon
classification is used to grade GM into four groups ranging from small breast enlargement with no skin excess to
marked enlargement with extra skin. Assessment should include BMI, secondary sexual characteristics and
examination of all areas of the breast (including the nipple) and axilla. Urgent referral is required if there are any
suspicious breast or testicular masses. Further investigation may not be required if the patient is within the age limit
for physiological GM and there are no additional clinical features of underlying disease or clear underlying drug
cause. Initial blood tests include morning testosterone level, liver, thyroid and renal function tests. Further
investigations and referral may be required on an individual basis.
Management: GM is transient in 90% of adolescents presenting to primary care and treatment should be delayed
in these patients unless symptoms persist for >2 years. Men with pathological GM need referral to an appropriate
specialist for treatment of the underlying cause; alternative treatment should be offered to men with GM likely to be
secondary to drugs. The clinical course of GM is proliferation of glandular tissue followed by fibrosis. Medical
management of GM is associated with a high success rate but once fibrosis occurs it is largely ineffective and
surgery is required. A number of medications are used for the medical management of GM including danazol,
clomiphene and tamoxifen; however they are not authorised for this indication. Tamoxifen is the most widely used
and response rates of up to 95% have been reported; it has also been used in patients with prostate cancer on
antiandrogen treatment who develop GM.
Update on influenza. A recent article provided a clinical update on influenza
(BMJ 2016; 355:i6258). Influenza is an acute viral infection of the respiratory tract that
spreads easily from person to person. Clinical features of influenza infection include
sudden onset of fever, myalgia, headache, malaise, dry cough, sore throat and nasal
congestion; GI symptoms are also common. The incubation period is 1-4 days; viral
shedding (when the virus is infectious) usually occurs from one day before, to 5-7 days after, the onset of
symptoms. Influenza is usually self-limiting in healthy individuals with recovery in 3-7 days. However, it can
cause severe illness or death, particularly in high risk populations; elderly people, children <6 months old,
pregnant women and people with chronic conditions or immunosuppression are all at increased risk of
complications. Minor changes that occur in virus proteins between influenza seasons (“antigenic drift”)
result in annual epidemics with winter peaks in Nov to April in northern hemisphere temperate regions like
Ireland. Pandemics (i.e. global epidemics) occur when a new influenza A subtype emerges abruptly due to
a major shift in the proteins on the virus surface (often because of combination with viruses circulating in
animals). Since most people have no immunity to the new subtype, infection spreads quickly. Treatment of
uncomplicated influenza in healthy individuals is supportive and includes antipyretics, adequate fluid intake,
rest and staying off work or school until 24 hours after resolution of fever in order to limit spread to others.
Most randomised trials of antiviral agents have been conducted in otherwise healthy individuals and have
shown modest reductions in symptom duration. Data from observational studies and other trials suggest
that antiviral treatment (oseltamivir / zanamivir) may reduce adverse outcomes in those at risk of
complicated influenza; treatment is most effective if started within 48 hours of symptom onset and should
not be delayed while awaiting results of investigations. Some patients may require antibiotic therapy to treat
secondary bacterial infections. Antiviral agents may also be used for post-exposure prophylaxis in at-risk
groups (The Summary of Product Characteristics for each antiviral agent at www.hpra.ie provides further
details). Prevention: Vaccination is the most effective means of preventing influenza and its complications.
It provides seasonally variable protection (estimated 60% for this season) in those < 65 years of age.
Although protective efficacy is lower in older age groups, influenza-related mortality and morbidity are
significantly reduced with vaccination. Annual influenza vaccination is strongly recommended for those
aged >6 months who are in the at-risk groups and for all health care workers. The current guidance on
influenza vaccination in Ireland is outlined in the Immunisation Guidelines at:
www.hse.ie/eng/health/immunisation/hcpinfo/guidelines/chapter11.pdf. The ideal time for vaccination
is before the influenza season (Sept to Oct); however the vaccine may be given until the end of April.
There are two types of vaccine available in Ireland: inactivated trivalent vaccine and live attenuated
influenza quadrivalent vaccine (LAIV). LAIV should not be used below 24 months of age because of
safety concerns regarding increased rates of hospitalisation and wheezing in this population. These
vaccines should not be given to those with a history of severe allergic (anaphylaxis) reaction to a previous
dose of the vaccine or any of its constituents; however people with egg allergy can get seasonal flu vaccine
(see the Immunisation Guidelines for full details on this). [More information, including downloadable patient
leaflets is available at: www.hse.ie/eng/health/immunisation/pubinfo/fluvaccine/ ]
Antibiotics for the sexual partners of women with bacterial vaginosis?
Bacterial vaginosis (BV), which has a worldwide prevalence of 10-50%, results in an
imbalance of the normal vaginal flora. Micro-organisms associated with BV have been isolated
from the normal flora of the male genital tract; therefore the treatment of sexual partners (SPs) might play a
role in the effective management of BV. A recent Cochrane review evaluated the safety and efficacy of
concurrent antibiotic treatment for the SPs of women undergoing treatment for BV (N= 7 randomised trials,
1026 participants). Compared with placebo, antibiotic treatment for SPs had no effect on clinical or
symptomatic improvement in women treated for BV, regardless of the time period (tested until after the
fourth week); moreover, treatment of SPs had no apparent effect on the recurrence of BV up to 12 weeks
after treatment, but increased the frequency of minor adverse events reported by SPs.
[Editor’s note: the full review is available in the Cochrane library (accessible via www.hrb.ie in Ireland)].
Every effort has been made to ensure that this information is correct and is prepared from the best available resources at our disposal at the time of issue.
References are available on request. This newsletter is produced by the National Medicines Information Centre, St. James’s Hospital (SJH) Dublin 8 and Dept of
Therapeutics Trinity College, Trinity Centre, SJH. Tel: Direct Line (01) 473 0589 or 1850 727 727 Fax: (01) 473 0596 Email: [email protected]