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Hormone replacement therapy

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Hormone replacement therapy

Hormone replacement therapy refers to any form of hormone therapy wherein the patient, in the course of medical treatment, receives hormones, either to supplement a lack of naturally occurring hormones, or to substitute other hormones for naturally occurring hormones. Common forms of hormone replacement therapy include:

Rodent studies for HRT

Many studies on the effects of Hormone Replacement Therapy (HRT) have been conducted on rats. Predominantly, these studies have looked at the effects of estradiol, a type of estrogen, on rats’ performances on various tasks. Often, the rodents will be ovariectomized, meaning they have their ovaries removed. This prevents the production and release of estrogen and progesterone, and mimics the occurrence of menopause in human females. Once the ovaries have been removed, researchers will administer estrogen, progesterone, or both to see what the effects are on the rats’ behaviors. Rats are good animal models because they have similar cognitive deficits to humans as they age, and administering hormone therapy to them is easy.[2]

Overall, the results of these studies are non-conclusive. Some studies find impairments due to the HRT, where others find improvements. A common theme that runs through many studies is that rats that are given HRT perform better on tasks activating the hippocampus, and worse on tasks involving the prefrontal cortex. For example, Wang et al. (2009) found that ovariectomized rats that were exposed to estradiol did considerably worse than rats who were not exposed to estradiol, on a delayed spatial reasoning task – a task that activates the prefrontal cortex.[3] Another study that looked at the effects of estradiol in ovariectomized rats, found that when HRT was administered immediately following the removal of the ovaries, there was a decrease in anxious and depressive behaviors, while also improvement on cognitive performance on an object-placement task (though this was a hippocampal-based task).[4] Hence, the timing of the hormone replacement therapy and the activated brain regions are significant factors in assessing effectiveness of HRT. Another important aspect is whether or not the treatment is chronic or cyclic. Chronic treatment is daily doses of the hormone, while cyclic treatment is based on the normal cycling patterns of that hormone. One study found that the group of rodents, who received estradiol and a type of progesterone chronically, performed the worst on the maze task; whereas, the group who received only estradiol cyclically showed some improvements.[5]

More research in this area is needed. Some important results can be gathered from these rodent studies though. First, that differing brain regions may respond in a variety of ways to HRT. Second, that the timing of the therapy is integral to the chances of success. Third, that how the hormones are administered, either chronically or cyclically, may make an important difference in their effectiveness.

Effects on women

As recently as 2005 women have had a positive attitude towards hormone replacement therapy but based on the empirical data these attitudes may be overly optimistic.[6] There is still much to learn about how HRT affects people. In the combined hormone trial, the WHI tested only one estrogen (Premarin) and one progestin (Provera), in a single pill (Prempro), at a single dose (0.625 mg Premarin and 2.5 mg Provera). Therefore the results are not reliable nor representative.

To avoid HRT risks it is essential to use the most effective delivery method of both estrogen and progesterone. Bioidentical estradiol (estrogen) when taken orally is converted in the liver to estrone, a weaker bioidentical estrogen. However when estrogen as estradiol is used transdermally as a patch, gel, or pessary, it enters the bloodstream as bioidentical estradiol. When estrogen is ingested it is subjected to first pass metabolism (Phase I drug metabolism) and is processed through the liver. This first pass metabolism stimulates proteins associated with heart disease and stroke, such as C-reactive protein, activated protein C, and clotting factors. Using a patch, gel or pessary to take estrogen avoids first pass metabolism and the risks associated with it and the same level of blood concentration can be achieved avoiding the serious side effects associated with oral estradiol HRT. Current research shows that the transdermal route of estradiol administration can also be advantageous for women with diabetes, hypertension and other cardiovascular risk factors, as those risks increase with advancing age.[7] Women taking bioidentical estrogen, orally or transdermally, who have a uterus must still take an FDA-approved progestin or micronized progesterone to lower the risk of endometrial cancer. The natural, plant-derived progesterone creams sold over the counter contain too little progesterone to be effective. Wild yam (Dioscorea villosa) extract creams are not effective since the natural progesterone present in the extract is not bioavailable. [8]

Past research has highlighted potential risks of HRT however the principal results from the Women's Health Initiative Randomized Controlled Trial concluded that estrogen in combination with micronized progesterone is not associated with an increased risk of breast cancer.[9]

A study where women going through menopause using HRT with Progestin as a major component of the therapy showed a few negative effects on hearing, which highlights the importance of choosing bioidentical progesterone instead of synthetic progestin. Not only does the Progestin decrease the functionality of many regions of the ear it also reduces the effectiveness in parts of the central nervous system used for hearing.[10] Also in some situations it has been shown that menopausal women who are caregivers and receive HRT can have an increased chance for cardiovascular issues. As caregivers it is implied that they have more acute stress in their lives and that acute stress along with the HRT is priming negative cardiovascular effects.[11]

Recent research done by the Million Women Study, funded by Cancer Research UK has proven that certain forms of HRT increase the risk of endometrial (womb) cancer. However, previous research has shown that the combined type of HRT poses a greater breast cancer risk than tibolone or oestrogen (estradiol)-only HRT and, because breast cancer is more common than endometrial cancer, the researchers believe that when considering the overall effect of HRT it is important to look at both breast and endometrial cancer.[12] However this study was conducted using oral estradiol instead of transdermal estradiol which avoids the risks which the study highlights. Again, this shows that the combined estrogen patch (such as Evorel® Conti) or gel (ESTROGEL PROPAK™ - 17ß-estradiol and micronized progesterone) is the preferable treatment choice.[13]

The Society of Obstetricians and Gynaecologists of Canada recommends Transdermal Estrogen and Micronized Progesterone as a first line hormone therapy option stating that the overall benefits of this therapy include reduction of vasomotor symptoms (hot flashes), lower risk of osteoporotic fractures, lessening of urogenital atrophy, lowering somatic pain and arthralgia, lowering the risk of colorectal cancer and mood stabilisation.[14]

There is a structural difference between hormone therapies that are bioidentical and those that are non-bioidentical, as non-bioidentical are responsible for side effects and health risks in humans. However, they can have positive health benefits for women, and bioidentical hormones can be customized from individual to individual. [15]

Hormone replacement therapy has been shown to have other beneficial effects. In a study women taking estrogen through HRT showed that the estrogen positively affects the prefrontal cortex by boosting the working memory. This suggests that estrogen may play a key role in certain frontal lobe functions in women.[16] Women using HRT after menopause have no additional weight gain compared to women who do not use HRT.[17] Also women who use HRT with an estrogen component show positive effects in their sex life (mainly increasing their sex drive and sexual sensitivity) but the effects are inconsistent across women. These sexual improvements may dissipate after receiving some forms of HRT for extended periods of time.[18]

See also


  1. ^ Shuster, Lynne T.; Rhodes, Deborah J.; Gostout, Bobbie S.; Grossardt, Brandon R.; Rocca, Walter A. (2010). "Premature menopause or early menopause: Long-term health consequences".  
  2. ^ Lowry, N. C.; Pardon, L. P.; Yates, M. A.; Juraska, J. M. (2010). "Effects of long-term treatment with 17β-estradiol and medroxyprogresterone acetate on water maze performance in middle aged female rats". Hormones and Behavior 58: 200–207.  
  3. ^ Wang, V.C.; Neese, S.L.; Korol, D. L.; Shantz, S.L (2009). "Chronic estradiol replacement impairs performance on an operant delayed spatial alternation task in young, middle-aged, and old rats". Hormones and Behavior 56: 382–390.  
  4. ^ Walf, A. A.; Paris, J. J.; Frye, C. A. (2009). "Chronic estradiol replacement to aged female rats reduces anxiety-like and depression-like behavior and enhances cognitive performance.". Psychoneuroendocrinology 34: 909–916.  
  5. ^ Lowry, N. C.; Pardon, L. P.; Yates, M. A.; Juraska, J. M. (2010). "Effects of long-term treatment with 17β-estradiol and medroxyprogresterone acetate on water maze performance in middle aged female rats.". Hormones and Behavior 58: 200–207.  
  6. ^ Herdis, S; O.F. Ragnar (2005). "Women’s attitudes to hormone replacement therapy in the aftermath of the Women’s Health Initiative study.". ISSUES AND INNOVATIONS IN NURSING PRACTICE 54 (5): 572–584. 
  7. ^ L’Hermite, M. (August 2013). "HRT optimization, using transdermal estradiol plus micronized progesterone, a safer HRT". Climacteric (Informa Healthcare) 16 (S1): 44–53.  
  8. ^  
  9. ^ Rossouw, Jacques E. (July 2002). "Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women". JAMA (The American Medical Association) 288 (3): 44–53. Retrieved September 21, 2014. 
  10. ^ Guimaraes, P.; S.T. Frisnina, F. Mapes, S. F. Tadros, R. Frisina, and R. D. Frisina (2006). "Progestin Negatively Affects Hearing in Aged Women". Proceedings of the National Academy of Sciences of the United States of America 103 (38): 14246–14249.  
  11. ^ Aschbacher, K.; R. Kanel, P. J. Mills, S. Hong, S. K. Roepke, B. T. Mausbach, T. L. Patterson, M. G. Ziegler, J. E. Dimsdale, S. Ancoli-Israel, and I. Grant (2008). "Combination of caregiving stress and hormone replacement therapy is associated with prolonged platelet activation to acute stress among postmenopausal women.". Psychosomatic Medicine 69 (9): 910–917.  
  12. ^ [1]
  13. ^  
  14. ^  
  15. ^  
  16. ^ Duff, S. J.; E. Hampson (2000). "A Beneficial Effect of Estrogen on Working Memory in Postmenopausal Women Taking Hormone Replacement Therapy". Hormones and Behavior 38 (4): 262–276.  
  17. ^ Reimer, R.A.; C. T. Debert; J. L. House; M. J. Poulin (2005). "Dietary and metabolic differences in pre-versus postmenopausal women taking or not taking hormone replacement therapy". Physiology & Behavior 84 (2): 303–312.  
  18. ^ Sarrel, P. (2000). "Effects of Hormone Replacement Therapy on Sexual Psychophysiology and Behavior in Postmenopause". JOURNAL OF WOMEN'S HEALTH & GENDER-BASED MEDICINE 9. 
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