Jared Kaltwasser

A new report lends evidence to concerns that 

 (Propecia, Proscar) might lead to an increased risk of suicide and psychological adverse events.

The report suggests the risk is particularly evident in younger patients, though it is possible that the apparent correlation may be due to stimulated reporting.

Finasteride is approved to treat androgenetic alopecia (male-pattern baldness) and benign prostatic hyperplasia (BPH). It has been on the market for nearly 3 decades, but concerns began in 2011 when a postmarketing report was sent to the US Food and Drug Administration (FDA) suggesting that the drug might increase the risk of depression, self-harm, and suicide.

That led to the issuance of warnings from regulators in a number of countries, including the UK and Canada. However, 

Corresponding author Quoc-Dien Trinh, MD, of Harvard Medical School, and colleagues explained that there is a plausible biological explanation for the link. Finasteride is a 5ɑ-reductase inhibitor (5ARI).

“Some reports suggest that men with depression have lower levels of the neurosteroid allopregnanolone, which is produced by the 5ɑ-reductase enzyme and has antidepressant and anxiolytic effects,” they said.

The authors decided to study the question by using the VigiBase database, which collects data on drug-reaction pairs, and includes more than 20 million safety reports covering more than 40 years. The investigators only excluded duplicate records from their analysis, otherwise including all patients prescribed finasteride for any reason at any dose.

Those data were then stratified by indication (BPH and/or alopecia) and age (45 and younger versus over 45). Finasteride signals were compared with those of drugs used for similar indications, but which use different mechanisms, as well as 

, which has a similar mechanism of action and adverse event profile. Those data were analyzed alongside reports of suicidality before and after 2012.

All told, the search yielded 356 reports of suicidality and 2926 reports of psychological adverse events.

The findings were characterized in terms of reporting odds ratio (ROR), a surrogate measure of association used in disproportionality analysis.

The authors found an ROR of 1.63 for suicide among patients who took finasteride, as well as a 4.33 ROR for psychological adverse events. Younger patients (ROR, 3.47) and those with alopecia (ROR, 2.06) had higher disproportionality signals for suicidality, compared to older patients and those with BPH. The data also showed, however, that reports of such adverse events increased significantly following 2012, the year after the post-marketing report was submitted.

Trinh and colleagues noted that a similar analysis for minoxidil, an alopecia drug with a different mechanism of action, did not show a link with suicidality.

“Taken together, our findings suggest that the disproportional reporting of suicidality and psychological adverse events in association with finasteride use could potentially be attributed to unique characteristics of the drug in young patients with alopecia,” they said.

The new analysis also found no disproportionate incidence of suicidality or psychological risk for dutasteride, another 5ARI. That finding differs from some earlier research that suggested the problem might be with 5ARIs as a category, rather than any single medication. Trinh and colleagues said stimulated reporting caused by publicity about finasteride may have contributed to their results.

Though Trinh and colleagues said stimulated reporting may have influenced the data, the signals associated with finasteride are sufficient to warrant further investigation and close monitoring of patients prescribed the drug, especially if they are 45 years old or younger and being treated for alopecia.

Investigation of Suicidality and Psychological Adverse Events in Patients Treated With Finasteride

Articles

The risk of suicidality and psychological adverse events appears to be particularly high in younger men with alopecia who are given finasteride.

Study Supports Potential Link Between Finasteride, Psychological Adverse Events

People who use electronic cigarettes face an increased risk of 

, regardless of whether they also smoke traditional cigarettes, according to a new study.

The research adds important new data about the health effects of the relatively new device.

E-cigarettes first came on the market in the US in 2007. While the devices have been shown to reduce a user’s exposure to toxic substances when used in place of traditional cigarettes, an 

 has suggested that e-cigarettes come with significant health risks of their own. Among the problems with e-cigarettes is the fact that many contain volatile organic compounds, heavy metals, and ultrafine particles that are believed to have negative impacts on the lungs, airways, and immune system.

Corresponding author Andrew C. Stokes, PhD, of the Boston University School of Health, and colleagues, sought to figure out what effect, if any, e-cigarette usage had on respiratory conditions such as chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, and asthma.

To answer their question, the investigators used data from the Population Assessment of Tobacco and Health (PATH) study, a nationally representative study of adults in the United States. The study was conducted in 4 “waves” between 2013 and 2018. All subjects included in the study had no prevalent respiratory conditions at the study’s baseline.

All told, the investigators identified 21,618 subjects, of whom 11,017 were men and 12,969 were non-Hispanic and white. Most of the subjects (14,213) said they had never used e-cigarettes. Another 5076 subjects said they had previously used e-cigarettes but had given up the habit. Only 2329 were current e-cigarette users at the start of the study.

After adjusting for the use of traditional cigarettes and other related products , the investigators found patients who had previously or currently used e-cigarettes had significantly higher risks of respiratory disease: former users had an incident risk ratio (IRR) of 1.28, and current users had an IRR of 1.31 (all ratios had confidence intervals of 95%). Even among patients who self-reported being in “good health,” the IRR for former and current e-cigarette users was 1.21 and 1.43, respectively.

When broken down by specific conditions, the authors found current e-cigarette users were at the greatest risk of emphysema (IRR, 1.69) and COPD (IRR, 1.57), followed by chronic bronchitis (IRR, 1.33) and asthma (IRR, 1.31).

Stokes and colleagues wrote that it’s logical that the risk of respiratory conditions would vary from disease to disease, given the different pathologies of the various conditions. For instance, they noted that asthma is typically diagnosed in childhood.

“In contrast, COPD typically develops in mid- to later life, characterized physiologically by incompletely reversible airflow limitation by a progressive 

The strengths of the study, according to the investigators, were the nationally representative sample, and the careful adjustment for cigarette smoking, thereby better isolating the precise risk added by e-cigarette use. However, they said there are also a number of limitations, such as the reliance on self-reported tobacco-usage and diagnostic data, and the relatively short follow-up period.

Nonetheless, Stokes and colleagues said their data made a compelling case that e-cigarettes, like traditional cigarettes, create a serious public health burden.

“These findings add important evidence on the risk profile of novel tobacco products with respect to respiratory outcomes,” they concluded.

Association of Electronic Cigarette Use With Incident Respiratory Conditions Among US Adults From 2013 to 2018

Even study enrollees who never smoked traditional cigarettes face a heightened risk of respiratory disease if they used e-cigarettes.

E-Cigarettes Raise Respiratory Risk for Current, Former Users

 public health burden of indoor air pollution is decreasing, but the issue remains a major concern in the poorest regions of the world, according to a new study.

More than one-third of the world’s population (3 billion people) use polluting fuels like wood, coal, crop waste, and animal dung to heat their homes and cook. This translates into indoor air pollution that leads to significant 

, pediatric, and maternal disease among those exposed to the pollution.

The fact that indoor air pollution is dangerous is not a new discovery, but corresponding author Anoop S.V. Shah, PhD, of the London School of Hygiene and Tropical Medicine, wanted to get a more up-to-date picture of the extent to which such indoor pollution continues to burden global public health.

To do so, they conducted a meta-analysis of 476 studies, collectively covering 15.5 million participants from 123 countries. Using that data, they sought to compare the risk of common adverse outcomes due to exposure to indoor air pollution versus the risk of those outcomes absent any exposure to air pollution. Their findings were based on the years 2000-2017.

The investigators found a number of health problems associated with indoor pollution. Among them were asthma (relative risk [RR]: 1.23), 

 in adults (1.53) and children (1.39), chronic obstructive pulmonary disease (1.70), lung cancer (1.69) and tuberculosis (1.26). Higher rates of low birth weight, cardiovascular mortality, stillbirth, and other health consequences were also identified, among others. All RRs were calculated with 95% confidence intervals.

In the year 2017, Shah and colleagues concluded, indoor air pollution contributed to 1.8 million deaths and 60.9 million disability-adjusted life-years (DALYs).

However, the impact was disparately spread across the globe; 60.8 million of the 60.9 million DALYs occurring in low- and middle-income countries (LMICs), and just 0.09 million DALYs in high-income countries.

Though the burden of indoor air pollution remained high, it was on the decline. Shah and colleagues found indoor air pollution-related mortality dropped 36% between 2000 and 2017, and pollution-related disease burden dropped by 30%. Again, however, the greatest improvements were seen in high-income countries.

“The burden of disease from household air pollution is almost exclusively borne by LMICs where there is little access to electricity or gas cooking,” Shah and colleagues wrote. “Paradoxically, the greatest relative reduction in burden attributable to household air pollution was observed in Europe where the burden was the lowest.”

The investigators added that some efforts to ameliorate the problem in LMICs might not be having the expected outcomes. They noted that the World Health Organization recommends transitioning from polluting fuels to clean-fuel technology in households that burn fuel to heat their homes or cook. However, Shah and colleagues found that the implementation of biomass-fueled cookstoves, which are billed as cleaner, did not lead to an improvement in outcomes.

Shah and colleagues said their analysis shows that it is important that interventions are put in place, but also that those interventions can be linked with demonstrated improvements in the health of the people they are intended to benefit.

“There is an urgent need for evidence-based policy and decision-making to ensure children and adults living in LMICs have clean air to breathe in their homes,” they said.

Adverse health effects associated with household air pollution: a systematic review, meta-analysis, and burden estimation study

Mortality linked to household air pollution has dropped by more than one-third in the past 2 decades, but the greatest improvements have come in countries where such pollution is not a major problem.

Indoor Air Pollution Decreasing, But Low-Income Countries Still Bear the Burden

New research adds to the case that patients with 

 especially women, face a higher risk of fibromyalgia syndrome (FMS) than the general population.

The study found the prevalence could be roughly 1 in 3, though that figure was based on a small sample size of just 82 patients with CU.

Co-authors Dr. Abdulsatar J. Mathkhor and Dr. Jinan Q. Mohammed, both of the Basrah Teaching Hospital, in Iraq, explained that there are a number of clinical and pathological features shared by FMS and CU. For instance, they said both cutaneous nerve fibers and mast cells play important roles in cutaneous inflammation, including CU and FMS. Both conditions are chronic and can affect quality of life, but neither is well understood by scientists.

Mathkhor and Mohammed wanted to gain a better understanding of potential links between the 2 conditions. To do so, they constructed a prevalence study, recruiting 82 patients with CU and 86 healthy controls.

All patients underwent autologous serum skin tests and were assessed using the urticaria total severity score (TSS). 

 was noted for each patient, and each patient was asked questions regarding the associated clinical features of FMS according to the 1990 American College of Rheumatology classification criteria.

Fifty of the 82 patients with CU (60.9%) reported widespread pain, but only 28 of those patients (34.1% of the total CU cohort) met the criteria for FMS. Of those 28 patients diagnosed with FMS, 20 (71.4%) were women.

Among the control group, only 10 patients (11.6%) reported widespread pain, and just 2 (3.5%) met the criteria for FMS.

Relatedly, clinical features of FMS were more prevalent in the CU cohort than in the controls, regardless of whether the patients met the FMS criteria, as were positive skin tests and severe TSS.

Though the authors found a significant correlation between CU and FMS, they noted that a 

 calculated the rate of FMS among patients with CU to be upwards of 70%. That study had 126 patients in its CU cohort.

Still, Mathkhor and Mohammed said their findings were comparable to what other studies have found among patients with related disorders, such as rheumatoid arthritis and 

As for the reasons behind the apparent link between CU and FMS, the investigators posited that a common pathogenesis involving peripheral nerves and different neurotransmitters might be a factor.

Another possibility is that the link has to do with the role of mast cells in the pathogenesis of both disorders, as separate studies have recently linked mast cells with both FMS and CU.

Mathkhor and Mohammed also identified one correlation that had not previously been reported in the literature. They found FMS severity was associated with TSS in patients with CU. That finding warrants additional study.

“There are remarkable similarities between CU and FMS that necessitate further clinical and laboratory studies with a larger study population to explain the exact relationship between these two disorders,” they concluded.

Prevalence of fibromyalgia syndrome in chronic urticaria

A new study confirms the link between chronic urticaria and fibromyalgia, though the correlation is not as strong as in a previous study.