Harmone Therapy Side Effects


Estrogen Deficiency

Fuller Albright first recognized the association between osteoporosis and estrogen deficiency in 1941. It is widely accepted that estrogen deficiency plays a central role in the pathogenesis of osteoporosis and that estrogen therapy is effective in preventing menopausal bone loss and reducing fracture risk. The menopause is the transition from the reproductive to the nonreproductive stage of a woman’s life, characterized clinically by permanent cessation of menstruation. The decline in ovarian activity may begin as early as 35–40 yr of age, long before menopause in most women. However, there is conflicting evidence as to when bone loss starts and whether premenopausal bone loss occurs. Most studies, however, have demonstrated that during and after menopause there is an accelerated rate of bone loss in the spine, with rates of between 1 and 6% during natural menopause and as high as 10% after oophorectom. A longitudinal study indicated annual rates of loss from the proximal radius in excess of 1% in the majority of postmenopausal women. The femoral neck shows annual rates of loss similar to those observed for the radius. Thus, the majority of evidence not only supports increased rates of bone loss during and after menopause, but that the highest rates occur in trabecular bone. This bone loss may continue for the next decade, accounting for 20–30% loss in cancellous (trabecular) bone and 5–10% loss in cortical bone The median age at menopause in most industrialized societies occurs around 50 yr.  Because the average life expectancy of women is approx 75 yr, most women will be postmenopausal for one-third of their lifetime.


Harmone Therapy Side Effects

Estrogen Therapy, Estrogen/Progestin Therapy, Bone, and Fracture Risk

Estrogen plays a critical role in bone health as evidenced by an accelerated loss in bone mass during the perimenopausal years. Estrogen alone or in combination with progestin prevents bone loss at the hip and spine and reduces hip fracture rates . The mechanism of estrogen to reduce bone loss is unclear, but locally active growth factors and cytokines modulate its effects on osteoblasts and osteoclasts . Although estrogen deficiency plays a key role in osteoporosis and other menopause-related chronic diseases, HT increases the risks of breast and uterine  cancer and is often accompanied by side effects. Indeed, HT or estrogen therapy alleviates vasomotor symptomsexerts some cardioprotective effects, and prevents bone loss. Yet, because of adverse effects as revealed by results from the WHI and the fear of cancer, noncompliance is a major obstacle with traditional HTs. Indeed, the global index of benefits and risks of HT in the WHI revealed a net harm (hazards ratio 1.15, 95% CI 1.03–1.28) and women taking HT had an increased risk of breast cancer , coronary heart disease, stroke , and venous thromboembolism (double). However, women taking HT and 24% decline in hip, forearm, vertebral, and total fracture rate, respectively, and 37% decline in colorectal cancer rate.

Menopause, Hormone Therapy, and Calcium Homeostasis

Studies by Heaney and co-workers confirmed that ovarian failure was associated with a 20% increase in bone resorption and a 15% increase in bone formation, leading to a net loss of bone. Calcium balance averaged –0.020 g/d in 207 studies with premenopausal women, whereas this balance was significantly more negative (p < 0.02) at –0.043 g/d in 41 studies with postmenopausal (untreated) women. These alterations in skeletal metabolism are accompanied by an increased urinary loss of calcium and decline in intestinal calcium absorption. The rise in urinary calcium with menopause is caused by a decline in tubular reabsorption of calcium, rather than a rise in filtered load These authors concluded that estrogens likely promote tubular reabsorption of calcium and that this renal calcium leak contributes to subsequent bone resorption with estrogen lack. Consequently, premenopausal and treated postmenopausal women have an apparent calcium requirement of 0.990 g/d, whereas untreated postmenopausal women require approx 1.504 g/d1. These changes in calcium metabolism are accompanied by alterations in the biochemical markers of bone turnover: serum osteocalcin, serum tartrate resistant acid phosphatase, serum alkaline phosphatase, urinary NTx, urinary hydroxyproline, and urinary pyridinoline and deoxypyridinoline (collagen crosslinks)

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