| Summary: | When this thesis was planned in 2000-2001 it was well known that bone loss accelerates after menopause, and is prevented by using hormone replacement therapy (HRT). Case reports of young men with estrogen receptor dysfunction or aromatase deficiency showed that estrogen was important for normal growth and maturation of the male skeleton. However, there were few prospective studies examining the contribution of endogenous sex steroids on bone loss and fracture risk in women, and no prospective study in men. We wanted to know if levels of sex steroids were relevant as predictors of bone loss and fractures and whether this knowledge could be useful for developing future treatment by low dose of HRT. During the work on this thesis results from a large randomized controlled trial assessed the risks and benefits of estrogen plus progestin treatment in 16,608 healthy postmenopausal women. The investigators concluded that the overall health risks exceeded benefits from the use of estrogen plus progestin in this group. They estimated hazard ratios with 95% confidence interval as follows: coronary heart disease 1.29 (1.02- 1.63); breast cancer 1.26 (1.00-1.59); stroke 1.41 (1.07-1.85); pulmonary embolism 2.13 (1.39-3.25); colorectal cancer 0.63 (0.43-0.92); endometrial cancer 0.83 (0.47-1.47) and hip fracture 0.66 (0.45-0.98). This publication led to a reassessment of the role of HRT, which was no longer recommended in women for fracture risk reduction alone. Left unresolved was the question whether women and men with low levels of circulating sex steroids have higher risk of bone loss or fractures. This was still relevant for our understanding of the contribution of sex steroids on bone fragility. From a clinical point of view it was interesting to know, if sex steroids are relevant predictors of bone loss or fractures, if these measurements could be useful in signalling the need for further investigation or treatment.
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