Thiazide diuretics are used commonly to treat
hypertension. Unfortunately, they also are known to elevate serum
cholesterol levels. Because serum
lipid fraction levels differ between the sexes, possible sex-related differences in
thiazide-induced changes in serum total
cholesterol (TC),
triglycerides (TG) and
high density lipoprotein cholesterol (HDL-C) levels were examined. Four groups of male and female hamsters were treated for a minimum of 3 months with
hydrochlorothiazide (
HCTZ) at zero, 1, 2 or 4 mg/kg/day. At zero dose, there was no difference in TG levels between the sexes; however, females had significantly higher TG concentrations than did males at 1, 2 and 4 mg
HCTZ (all p less than 0.05). Females demonstrate a significant dose response with HCL-C levels increasing with increasing doses of
HCTZ, (r = 0.983; p less than 0.02); in contrast males had a similar increase in HDL-C at all dose levels (all p less than 0.05) thus there was no demonstrable dose response (r = 0.539). Total
cholesterol concentrations were significantly higher in the females than in males (p less than 0.05) at all 3 dose levels as well as at zero dose. Further, the females demonstrated a direct dose response in TC levels (r = 0.986; p less than 0.02) while the males showed no such dose response (r = 0.824; p less than 0.01). Based on these findings we conclude that: 1)
HCTZ increases TG, TC and HDL-C levels in both male and female hamsters; 2) TC levels are higher in females than in males regardless of
HCTZ dose; 3) only females show a dose-dependent increase in HCL-C and TC in response to
HCTZ. These sex-related changes in
lipid fractions occurring with
HCTZ treatment, if they occur in humans, may contribute to sex-related differences in rates and severity of
atherosclerosis in
HCTZ-treated populations.