Introduction to Hormone Replacement Therapy As time goes on, the growing question for females reaching menopause is whether hormone replacement therapy (HRT) should be undertaken or not. There are various arguments about the validity, effectiveness and safety of HRT. Females reaching menopause should consider all sides before making a decision. This paper explains the symptoms of menopause and a brief overview of HRT and will attempt to help give information to those who are thinking of using HRT. HRT involves the use of hormones (estrogen and progesterone) to reduce symptoms of post-menopausal women. Common symptoms these individuals get are hot-flushes, changes in reproductive organs, cardiovascular disease, osteoporosis, nervousness, and depression. There is also an increased incidence of high blood pressure, stroke, and heart disease following menopause probably due to the removal of the protection estrogen affords. Treatment includes low-dose estrogen administration with some progesterone therapy and calcium supplementation. This therapy is protective of the breasts and uterus against cancer, deters the loss of bone, and increases HDL (high density lipoproteins, the good ones) and lowers LDL (low density lipoproteins, the bad ones) in the blood. Sometimes a topical vaginal estrogen cream is used to restore the vagina and external genitalia to a premenopausal state. One of the biggest problems with the use of HRT seems to be higher incidence of breast cancer. Some studies have shown that the use of HRT may not have any effect on individuals who have already been diagnosed and treated for breast cancer (DiSaia PJ, Brewster WR, Ziogas A, Anton-Culver H, 2000). Another study showed that based on the available evidence, the risk of breast cancer diagnosis is higher among women who have used hormonal replacement therapy than among women who have not. The risk increases with treatment duration, is reduced when treatment is stopped and disappears almost completely a few years post-treatment. The increase in the risk of breast cancer may be larger with estrogen-progestogen therapy than with estrogen alone. (Clavel-Chapelon F, Hill C, 2000; Raafat AM, Hofseth LJ, Haslam SZ, 2001; Persson I, 2000) Other researchers have suggested that the higher incidence is, however, very limited and not associated with a higher mortality because only low grade, slowly progressing, receptor positive cancers are increased. (Braendle W, 2000) Even though many research papers and reviews indicate the possibility of breast cancer, most indicate that further research must be done in order to determine what the mechanism is and whether there is a genetic component to it. Although one of the major possible side effects of HRT is breast cancer, there are many benefits to it. An important factor to consider is its effect on bone. As mentioned previously, the effects of HRT (specifically estrogen) has bone a sparing effect and helps deter osteoporosis. One study suggested that ERT can increase the fracture load and stiffness of trabecular bone by allowing bone formation to continue in previously activated bone remodeling units while suppressing the production of new remodeling units. (Krober MW, Lane N, Lotz JC, Thomsen M, 2000) Krober et al. (2000) also went on to say that it may be the mechanism by which estrogen and other antiresorptive agents increase bone mass, thus reducing the risk of osteoporotic fractures in postmenopausal women. Many other studies confirm that the antiosteoporotic effect of HRT is positive. (Heikkinen J, Vaheri R, Kainulainen P, Timonen U, 2000; Kamel HK, Perry HM 3rd, Morley JE, 2001) Cardiovascular disease (CVD) is an important health issue in our society. It is ranked as one of the top 5 causes of death and has also been an issue of study with respects to HRT. According to studies the use of estrogen in HRT actually aids in prevention of CVD. (De-Aloysio D, Gambacciani M, Meschia M, Pansini F, Modena AB, Bolis PF, Massobrio M, MaiocchiG, Peruzzi E, 1999; Rossouw JE, 1999; Rosano GM, Panina G, 1999). It is observed to cause a decrease in LDL and an increase in HDL. (De-Aloysio et al., 1999) The results of such changes fall outside the scope of this paper but it is important that HDL (good cholesterol) is retained and increased. It helps in removal of cholesterol from vascular walls thereby reducing the potential for cholesterol to plaque in artery walls. With estrogen being beneficial in the prevention of CVD, there is a plus side for the decision to use hormone replacement therapy. Hormone replacement therapy has recently been in the media because of its benefits to the neurological system, especially that of memory. It is believed that HRT may in fact help in reducing the risk for Alzheimer’s disease and dimentia. (Costa MM, Reus VI, Wolkowitz OM, Manfredi F, Lieberman M, 1999) The prevention of such a terrible condition such as dimentia and Alzheimer’s is a definite positive for HRT. It is believed that estrogen has a protective function for cognitive function. Estrogen may play a role in the pathophysiology of Alzheimer’s through improvement of cerebral blood flow, stimulation of the neuron or gliacyte and interaction with genetic factors. Most etiological studies of estrogen replacement therapy and Alzheimer’s have been retrospective studies. (Van-Duijn CM, 1999) There have been links of HRT to another compound in the body, namely IGF or Insulin-like growth factor. The relation to this hormone/peptide is that it is proposed to decrease bone mass to some degree. (Vesterguard P, Hermann AP, Orskov H, Mosekilde L, 1999) As well, it has been proposed that elevated estrogen levels cause an increase in IGF-I that may contribute to endometrial cancer via non-insulin-dependant diabetes. (Parazinni F, La Vecchia C, Negri E, Riboldi GL, Surace M, Benzi G, Maina A, Chiaffarino F, 1999) In the same light, another study found that both the nonoral and oral continuous combined estrogen-progestin therapies produced only minor changes in the circulating concentrations of IGF-I and its binding proteins. (Raudaskoski T, Knip M, Laatikainen T, 1998) Overall, it seems that there are mixed answers to the effects of HRT and IGF, however, it is important enough to mention because it may be a potential source of cancer for some females. Many forms of treatments have been proposed and are currently in use. Some of the newer avenues of thoughts revolve around the use of using plant estrogens or phytoestrogens. These estrogens are found abundantly in seeds, red clovers and soy. There are some speculations of whether to extract the active components (estradiol) and administer it pharmaceutically or to prescribe a diet high in phytoestrogens. (Adlercreutz H, Mazur W, 1997) Studies show that the use of phytoestrogens may in fact be beneficial over the androgenic counterpart because estradiol (the active component) seems to have an anticarcinogenic effect. (Horn-Ross PL, 1995; Musey PI, Adlercreutz H, Gould KG, Collins DC, Fotsis T, Bannwart C, Makela T, Wahala K, Brunow G, Hase T, 1995) As mentioned earlier, one of the down sides to using HRT was the potential increase in risk for breast cancer. However, it was found that countries that have the highest intake of phytoestrogens also have the lowest breast cancer rate. (Adlercreutz H, 1995; Adlercreutz H, Mazur W, 1997) These findings show great promises for the future. Ethics is another factor that is an important issue among females deciding to use HRT or not. There are ongoing debates about the use of animal hormones (like that of horses or pigs), synthetic creation, and phytoestrogens. Ethical concern arises with animal hormones because of possible cruelty of animals and regulatory procedures. Synthetic hormones are a concern for regulation and effectiveness as well as possible side-effects. The ethical concerns of phytoestrogen is the method of administration, regulation of “proper” amounts and regulation of sources. (Adlercreutz H et al., 1997) As an interesting side note, there was a study conducted that attempted to find out the most important reasons for participation in HRT. Most dominant reasons were reducing risk for Alzheimer's disease and osteoporosis; others included having more energy, improving self-care ability, and benefiting other women. Fear of cancer from postmenopausal estrogen was the predominant concern of 46% of nonparticipants and 78% of participants. Recommendation against participation or use of estrogen by a woman's personal physician was the most prevalent additional reason given for nonparticipation. This study concluded that disease prevention and improving self-care abilities were most important to participants. Fear of cancer was not a greater concern for nonparticipants than for participants and the role of the physician in older women's decision-making about use of postmenopausal estrogen seems to be important. (Jeffe DB, Binder EF, Williams DB, Kohrt WM, 2001) As we have discussed in this paper, there are many facets to consider when deciding to use hormone replacement therapy. Although there are many benefits such as decreasing the risk of CVD, dimentia, Alzheimer’s, and osteoporosis, the risk of breast cancer is high. However as mentioned above, promising studies show that there may be a way to eliminate the problem of breast cancer with the use of phytoestrogens. Although still being researched, the future of this source of estrogen is bright. The biggest question is whether taking the risk of getting breast cancer is worth getting the chance to lead a relatively normal life. Ethical concerns are more of an individual preference and moral belief, but need to be considered to some extent. If one does choose to use HRT, then the method of administering the hormones is the last factor. Hopefully this paper gave enough information for any female thinking about hormone replacement therapy to make an informed decision. REFERENCES:
Vesterguard P, Hermann AP, Orskov H, Mosekilde L (1999). Effect of sex hormone replacement on the insulin-like growth factor system and bone mineral: a cross-sectional and longitudinal study in 595 perimenopausal women participating in the Danish Osteoporosis Prevention Study. Journal of Clinical Endocrinology Metabolism. 84(7), 2286-2290. |