Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis

Abstract

The use of menopausal hormone therapy (MHT) has declined due to concerns about its potential side effects. However, its pivotal role in managing postmenopausal osteoporosis is gaining increased recognition. In this article, we explore how MHT assists postmenopausal women in maintaining bone health and preventing fractures. Recent research indicates that MHT significantly reduces the risk of fractures in women. This benefit is evident regardless of a woman's bone mineral density or their use of progestogens. However, there is limited evidence suggesting that the skeletal benefits continue once the treatment is discontinued. Possible complications of MHT include heart attacks, clots, strokes, dementia, and breast cancer. The most suitable candidates for MHT are women who have recently entered menopause, are experiencing menopausal symptoms, and are below 60 years of age with a minimal baseline risk of adverse events. The treatment is available to those who meet these criteria. For women undergoing premature menopause, MHT can be considered as a means to protect bone health, especially if initiated before menopause or if accelerated bone loss is documented soon after menopause. Such decisions should be made after evaluating individual risk factors and benefits.

Keywords: bone health; menopausal hormone therapy; osteoporosis; postmenopause.

Figure 1

Physiology behind fractures caused by osteoporosis.

Figure 2

(a) Influence that estrogens have on bone cells. (b) Alterations in cellular state brought on by estrogen fluctuations. Effects are shown with +E when estrogen is present, while effects are shown with −E when estrogen is not present. IL-1 is also known as TNF and OPG. Estrogen inhibits osteoclastogenesis and enhances osteoclast apoptosis. Estrogen inhibits osteoclastogenesis by blocking the production of IL-1 and TNF. It also increases the susceptibility of stromal cells and preosteoblasts to the effects of IL-1, which in turn blocks the production of M-CSF, RANKL, and possibly most significantly, IL-6. Furthermore, estrogen encourages the formation of OPG, which is a powerful inhibitor of osteoclastogenesis. Additionally, estrogen has the effect of making osteoclast precursors less sensitive to RANKL. Additionally, estrogen encourages osteoclastic apoptosis, which in turn shortens the lifetime of osteoclasts. It would indicate that TGF-b is the factor responsible for causing this impact [4].

Figure 3

There are several ways in which estrogen decline during menopause might have a negative impact on cardiometabolic health. The decrease in estrogen that occurs during menopause is thought to have direct impacts on the brain, including the potential to lessen satiety and, as a result, increase food intake; it also causes sleep disturbances and lessens muscle’s sensitivity to insulin. In addition, the melanocortin 4 receptor and the estrogen receptor- in the brain are responsible for estrogen’s ability to boost physical activity. This function may be lost after menopause. These alterations, taken together, are a contributor to the rise in visceral adiposity that is associated with menopause, as well as the risk of fatty liver disease. These, in turn, contribute to insulin resistance, which in turn leads to type 2 diabetes mellitus, a higher atherogenic lipid profile (lower HDL cholesterol, increased LDL cholesterol, and triglycerides), and systemic inflammation. Estrogen deficiency has been shown to directly affect arterial endothelial function, which, when combined with a lower lipid profile, raises the risk of CVD [20].

Figure 4

(a and b) An infographic that provides an overview of the classification of fracture risk based on the FRAX major osteoporotic fracture probability in postmenopausal women. The FRAX model is used for the first risk assessment, which only considers clinical risk variables. When the FRAX probability is in the red zone, this indicates a very high risk, and suggests that an initial course of anabolic medication followed by antiresorptive therapy would be warranted. If the FRAX probability is in the green zone, this indicates a low risk, and the patient should be counseled on how to improve their lifestyle, as well as their consumption of calcium and vitamin D, and the therapy of menopausal hormones. If the FRAX probability is in the intermediate (orange) zone, then a BMD examination and recalculation of the FRAX probability should be performed, including taking into account the femoral neck BMD. After recalculation, the risk may fall into the red zone (very high risk), the orange zone (high risk, which indicates starting antiresorptive treatment), or the green zone (low risk, either in the original green zone or in the original orange zone but below the intervention threshold). The red zone represents a very high risk, while the orange zone and green zone both advise initial antiresorptive therapy. Take note that individuals who have had a previous fracture due to fragility are classified as having at least a high risk, and depending on the FRAX likelihood, maybe even a very high risk. (c). Different treatment options are based on the classification of the patient’s risk of fracture. Regarding the various therapeutic approaches (such as bone resorption inhibitors, anabolic medicines, etc.) [71].