Risk of Thiazide-Induced Hyponatremia higher among Elderly Women: JAMA
Researchers have found in a new study that thiazide-associated hyponatremia shows strong age and sex dependence, with the highest risk observed in older adults, particularly women aged 80 years and above. It was found that while the absolute risk is minimal in younger adults, it becomes significant in older women, warranting consideration of alternative antihypertensives and close sodium monitoring after treatment initiation. The study was published in JAMA Network Open by Cecilia B. and colleagues.
Despite their common use as first-line therapy for hypertension, the pharmacological effects of thiazides, which promote the removal of sodium and fluids from the body, may sometimes cause hyponatremia, where the amount of sodium in the bloodstream drops dangerously low. Even though healthcare professionals have known about this adverse effect for some time now, no population-based risk estimates have been made available until now. To achieve a proper comparison of both patient cohorts, the research team used the propensity score-matched cohort design.
In total, 79,540 patients prescribed thiazide diuretics (median age 63; 51.9% female) were compared to the same number of people prescribed CCBs. Hyponatremia was considered profound when the serum sodium content fell below 125 mEq/L, while mild and moderate hyponatremia were set at 130 mEq/L and 135 mEq/L, respectively. Through these quantitative criteria, the researchers could study the effect of the drug on electrolyte balance for different age groups and genders.
Key findings:
Within the first two years of medication use, profound hyponatremia occurred in 0.80% of thiazide patients versus 0.46% of CCB patients.
But the average rates hid the true severity of the problem in older patients. In people over 80 years old, the rate of profound hyponatremia skyrocketed to 2.40%.
Women also experienced a higher prevalence, at 1.04% in comparison to men.
Perhaps the most revealing statistic was the analysis of "Number Needed to Harm" (NNH).
In elderly women more than 80 years of age, NNH of profound hyponatremia (less than 125 mEq/L) was found to be very low at 53.
It shows that out of every batch of 53 elderly women, one is suffering from profound hyponea.
The risk was even greater when the definition of profound hyponatremia extended to mild cases.
Thus, the NNH was 28 for <130 mEq/L and only 16 for <135 mEq/L.
In women under 65 years old, however, the NNH dropped to 790, showing that the negative effect of thiazides on electrolytes is relevant primarily to elderly patients.
The link between newly started thiazide diuretics and hyponatremia among those under the age of 65 is virtually non-existent, but becomes a significant issue among older patients, particularly females. The above-described study is the one that fills in the gap of absolute risk figures that were previously not known to clinical practice. Although thiazides are effective and relatively cheap to use in blood pressure management, their usage by "oldest old" patients needs to involve more caution. Using demographic risk information will enable clinicians to make the right decisions while dealing with hypertension cases without compromising electrolyte balance.
Reference:
Bergh Fahlén C, Falhammar H, Skov J, Lindh JD, Mannheimer B. Thiazides and Risk of Hyponatremia by Age and Sex. JAMA Netw Open. 2026;9(4):e264642. doi:10.1001/jamanetworkopen.2026.4642
