Follicle-stimulating hormone (FSH) may elevate LDL cholesterol levels by inhibiting hepatic cholesterol metabolism in postmenopausal women, new research published in the Journal of Clinical Endocrinology and Metabolism suggests.
Postmenopausal women tend to have higher total and LDL cholesterol levels, which put them at higher risk for cardiovascular diseases. Previous studies have tried to determine the cause of lipid changes during menopause and found that some women still develop dyslipidemia after undergoing hormone replacement therapy. Some studies have also found that FSH, which increases during menopause, is more strongly associated with health outcomes after menopause than estrogen, according to background information in the study.
“The huge menopausal endocrine change, especially sharply raising the serum FSH levels, exhibited negative effects on lipid levels,” the researchers wrote. “Our results indicate that FSH may interact with its receptors in hepatocytes and reduce [LDL receptor] levels, which subsequently attenuate the endocytosis of [LDL cholesterol], resulting in an elevated circulating [LDL cholesterol] level.”
The researchers examined serum FSH and lipid levels in 400 Chinese postmenopausal women aged 42 to 60 years who underwent hormone replacement therapy. They collected blood samples from the participants and took liver and ovarian tissue samples from women undergoing hepatectomy surgery. They used polymerase chain reaction (PCR) and western blotting to identify FSH receptor expression and LDL receptors in livers and HepG2 cells.
Results showed that postmenopausal women with serum FSH ≥78.3 IU/L had higher serum LDL and total cholesterol levels than women with lower FSH levels (P<.01).
The mean FSH concentrations decreased by 29.6% after treatment with estradiol valerate 1 mg tablets per day for 12 months. Women with FSH levels that decreased by more than 30% had significantly improved levels of total and LDL cholesterol.
In the HepG2 cells, the serum FSH inhibited the LDL receptors, and treating them with FSH receptor siRNA for 6 hours reduced the expression levels of FSH receptor mRNA and protein.
The results suggest that menopause-associated dyslipidemia could be caused by changing levels in FSH. The researchers also predict that hormone replacement therapy may have preventive effects in postmenopausal women with higher FSH levels, and these women should be encouraged to take hormone replacement therapy.
“This founding may indicate a novel mechanism of postmenopausal dyslipidemia and may provide a rationale for [hormone replacement therapy] inhibition of FSH levels targeted approaches for the clinical treatment,” the researchers concluded.