Facts and Fictions Surrounding Hormonal Replacement Therapy

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Introduction

Hormonal replacement therapy in women basically aims at providing sufficient female sex hormones notably estrogen and progesterone in women who are deficient due to congenital anomalies like hypogonadism, premature ovarian failure, menopause or the removal of ovaries surgically. Estrogen is a pre requisite for the normal female reproductive development and for the development of secondary sexual features.

Background

In pre-menopausal women who are incapable of producing sufficient female sex hormones estrogen therapy along with progestin (synthetic derivatives of progesterone) can be administered to imitate the natural cyclic pattern of these hormones in order to promote secondary sexual development but this therapy has to be continued throughout life. Hormonal replacement therapy for post menopausal women has become quite controversial due to the recent discoveries about some of the adverse effects associated with it. Initially hormonal replacement therapy was started in post menopausal women to curb some of the undesirable and distressing features that occur in many women after the cessation of their normal menstrual and ovarian cycles and the accompanying fall in blood levels of estrogen. These features range from vasomotor symptoms like hot flushes, atrophy of vagina, vulva, urethra and trigone of the bladder, decrease in the remodeling of bone leading to osteoporosis and increase in the risk of myocardial infraction and it was thought that exogenous estrogen might help ameliorate these.

Later research showed that some of the expected advantages of hormonal of therapy were non existential and it might incline women to more risks than benefits. Thus due to these findings there was a dramatic decline in its use from 16 million women in 2001 to just 6 million women in 2006 being prescribed this therapy in the USA. It has also been showed that the therapeutic effects and risks of hormone replacement therapy vary with the type of estrogen and progesterone used, the age of the patient when the therapy is started, the health status of the patient and the duration of treatment. HRT seems to increase the risk of breast cancer especially lobular carcinomas and ductal lobular cancer after it has been in use for around 5-8 year. It also leads to a higher risk of venous thrombo-embolism, deep vein and pulmonary thrombosis and stroke. This increase in risk is considerably higher in women during the first 2 years of treatment and in women who have other factors that predispose them to hypercoagulable states such as hereditary diseases which result in mutation of V Lieden factor and clotting factors. Studies have shown that if estrogen is used alone in HRT then there is a 3 to 6 fold increase in the chances of getting endometrial cancer after 5 years and more than 10 fold increase after 10 years of therapy. Therefore in the hormonal replacement therapy that are currently in use a progestin is always added to the estrogen to abate the chances of getting endometrial carcinomas in women who haven’t undergone a hysterectomy. In women who have had their uterus removed unopposed estrogen therapy is given as the addition of progestin might unfavorably change the lipid profile and decrease the desirable effects of estrogen on the lipid parameters.

Advantages of HRT

Hormone Replacement Therapy has showed to slow down the advancement of atherosclerosis leading to a lower incidence of coronary heart disease but this effect is only significant in women under the age of 60 and who also started HRT at an early age. In younger women this effect may be due to the estrogen receptors that help in maintaining the homeostasis of calcium ions in blood vessels. Results of later studies have showed little or no effect of estrogen on decreasing the risk for myocardial infarction so its role in controlling cardiovascular diseases in post menopausal women remains debatable. Estrogen decreases the rate of resorption of bone and is effective in decreasing the frequency of fractures. Thus it has proved to be effective for the treatment and prevention of osteoporosis but according to recent guidelines due to the recently elucidated detrimental effects other therapies such as treatment with drugs like alendronate should be considered first for the treatment of osteoporosis. Also a high calcium diet and exercise can slow down or halt the onset of osteoporosis without the need for HRT. In accordance with the America Menopause society HRT should be used with the lowest possible dose given for the shortest possible time to cure post menopausal symptoms like hot flushes and vaginal atrophy and to decrease many of its well established risks factors.

References

  1. Robbins and Cotran Pathological Basis of Diseases 8th edition
  2. Robbins Basic Pathology 8th edition
  3. Katzung and Trevor’s Pharmacology 9th edition
  4. Lippincott Pharmacology 4th edition