Long-term hypoparathyroidism complications differ by sex: Review
Chronic kidney disorder more likely in men; women may face higher fracture risk
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Men with chronic hypoparathyroidism may be more likely to develop chronic kidney disease (CKD), while women with the disorder may face higher risks of bone fractures, anxiety, and cognitive problems, according to a review study.
Researchers also found that menopause, disease duration, and the underlying cause of hypoparathyroidism may strongly influence the type and severity of complications.
“Available evidence suggests gender-related trends in long-term complications of chronic [hypoparathyroidism], but data are limited,” researchers wrote, highlighting that “gender-informed research is needed to support personalized management strategies.”
The study, “Gender differences in long-term complications of chronic hypoparathyroidism: a systematic review,” was published in the Journal of Endocrinological Investigation.
Chronic kidney disease affected up to 41% of patients
Hypoparathyroidism is characterized by low levels of parathyroid hormone, which helps regulate calcium and phosphorus levels in the body. More commonly, the disease develops as a complication of thyroid surgery. Other causes may be genetic or autoimmune, or the cause may be unknown, in which case it is called idiopathic.
Chronic hypoparathyroidism is associated with lifelong treatment mainly aiming to maintain normal calcium levels in the blood. While the possible complications of hypoparathyroidism are well-known, “potential gender differences in disease-related complications remain poorly defined,” researchers wrote.
To learn more, Italian researchers conducted a systematic review of published studies. Among the 42 included studies, a higher risk of kidney problems, including elevated urine calcium (hypercalciuria), kidney stones, and reduced kidney function, was associated with longer duration of hypoparathyroidism and long-term use of calcium and vitamin D supplements.
Hypercalciuria was reported in four studies, enrolling patients mostly with post-surgery hypoparathyroidism and disease duration between 6.5 and 9 years. Two studies reported significantly higher urinary calcium levels in females, whereas two did not report sex differences.
CKD affected up to 41% of the patients in the studies reporting such data. One study enrolling 3,372 patients followed up for a median of nine years showed that males had twice the risk of developing CKD and being hospitalized for CKD regardless of a surgical or non-surgical cause for the disease. These findings were confirmed in a study of 29 children in which males had lower kidney function.
“These data are consistent with some studies on the general population, in which male sex is recognized as a risk factor for faster decline in renal function,” the investigators wrote. However, a further study found no differences in the rate of kidney insufficiency.
Sex does not determine kidney stone risk in hyperparathyroidism
Seven studies analyzed how common kidney stones are in people with hypoparathyroidism. One study reported about twice the risk in males than females, while the remaining six found no differences. Taken together, the evidence suggests that, unlike in the general population, where males seem more likely to have kidney stones, sex does not determine that risk in people with hyperparathyroidism, the team wrote.
The risk of bone complications, particularly vertebral fractures in the spinal cord, was higher in people with idiopathic hypoparathyroidism, but not in those with post-surgery disease, according to a pooled analysis of seven studies.
Several studies reported a higher prevalence of vertebral fractures in postmenopausal women with post-surgery hypoparathyroidism (63%). But the condition was not associated with a higher risk for osteoporosis — weak and brittle bones, susceptible to fractures — in thyroid cancer patients, regardless of age and sex.
Some studies reported changes in bone microstructure and turnover (the continuous process of bone tissue being broken down and rebuilt), with menopause emerging as a stronger predictor of bone problems than sex alone.
Beyond sex alone, disease [cause], disease duration, and menopausal status may significantly influence the type and severity of complications.
Neurological complications like basal ganglia calcifications (calcium deposits that build up in brain structures controlling movement, emotions, and learning) did not differ consistently by sex. However, women appeared to be more vulnerable to cognitive impairment and neuropsychiatric issues such as anxiety.
The risk for cardiovascular complications was also higher in women with hypoparathyroidism in some studies, while others demonstrated that women experience a higher symptom burden and more severe functional impairment than men, as well as worse perceived health-related quality of life.
“Although the evidence is limited, males showed a higher prevalence of chronic kidney disease,” the researchers wrote. “In contrast, females more commonly displayed neuropsychiatric symptoms (anxiety, mood lability, cognitive dysfunction), skeletal complications (vertebral fractures, bone loss), and cardiovascular conditions. Beyond sex alone, disease [cause], disease duration, and menopausal status may significantly influence the type and severity of complications.”
