The Dilemma of Hormone Therapy in Menopause
Estrogen, the main hormone during a woman’s reproductive years, is no longer produced after menopause which is the cessation of periods. This deficiency of estrogen has an amazing wide range of effects on various tissues and organs of the body. The menopausal woman may have symptoms of which the most common is hot flushes. This is an intense sensation of heat on the upper part of the body, lasting up to few minutes, and coming on several times a day in severe cases. Around 45% of women report palpitations or ‘ghabrahat’ as the first symptom. Such women will require a cardiology checkup before attributing these to menopause. Complaints like frequency, urgency of
urination, repeated urinary and genital infections are very common, not responding to several courses of antibiotics. Dryness of the vagina makes sexual relationships painful. Dry eyes are also very common and one can often catch elderly women using eye drops to keep their eyes moist. Many women also complain of memory loss and other cognitive difficulties. Emotional instability and inability to cope are also due to estrogen deprivation. Sleep disorders are essentially due to night sweats and this leads to tiredness, lethargy and stress. Depression, however, is not directly linked to menopause and is more often due to social factors like retirement blues, financial insecurity, need to take care of old parents, and children doing away – ‘empty nest syndrome’.
Menopause has a negative effect on the connective tissues of the body. The skin becomes thin, parchment like with wrinkling. Osteoarthritis (inflammation of the joints) increases and those with Rheumatoid Arthritis find it worsening. More fat gets deposited in the abdominal area and in these ‘pear-shaped’ women blood pressures begin to rise, blood sugars are raised and lipids become abnormal. These 3 are the risk factors for heart attack which is the biggest killer of post-menopausal women, three times more common than all cancers put together.
The most important effect of estrogen deficiency is the thinning of bones, known as Osteoporosis, leading to fractures with little or no trauma – just a big sneeze or standing from sitting posture or a sudden jerk is enough to fracture a bone. The most common sites are the vertebrae in the backbone causing the woman to stoop or have a humped back with a consequent loss of height up to 6 inches. Other sites are the hip bone and the wrist. Even tooth loss is attributed to post-menopausal osteoporosis of the jaw bone.
Since all these problems are associated with deficiency of estrogen, it would be natural to presume that prescribing hormone replacement therapy (HRT) would be the simplest solution. All prescriptions, however, are governed and controlled by intense research and earlier research like the famous Nurses Health Study (NHS), showed beneficial effects of estrogen. And this has been the way till the results of a famous trial, the Women’s Health Initiative (WHI), were released in 2002. This trial showed that there seemed to be an increased risk of breast cancer, heart attack, and stroke in women taking hormone replacement therapy. As a result of this, the prescriptions for estrogen dropped worldwide. Both, the doctors and the patients were absolutely petrified to prescribe or take HRT.
This situation remained like this till major organizations, totally devoted to the health of the post-menopausal woman, began a review of all scientific data. These included independant menopause societies of North America, Europe, UK and Canada. The conclusions of all of them were similar to the recommendations released by the International Menopause Society (IMS) after its conclave in Vienna in 2004. The main issues that were addressed were: Does HRT increase chances of breast cancer and cardiac risks?
The 2 landmark trials which have influenced prescribing patterns over the last few years have been the WHI Trial 1 (2002, Estrogen + Progestrogen), WHI 2 (2004, Estrogen alone) and the Million Women Study, 2003. Both were found to have significant flaws. In WHI 1, breast cancer was ‘apparently’ increased because it was decreased in the control group. Therefore this was no ‘real’ increase. In WHI 2, breast cancer was 23% lower! The increase of breast cancer found in the MWS was only in the first year of use of HRT. It is possible that these were pre-existing cancers and HRT could not be held responsible for their occurrence. For cardiac risks, 3 major studies were reanalyzed including the WHI Trial. It became very clear that increased cardiac risks were because the average age of the population studied was around 65 years. On the other hand, the NHS, which had found beneficial effects on the heart, had studied a much younger population who still had early symptoms of menopause. It is possible that the physiology of the early menopausal years is different from late menopause. The results of the WHI can certainly not be generalized or extrapolated to populations it did not study. Therefore all conclusions drawn now became invalid. The fears about HRT began to recede and the pendulum began to swing back in favour of HRT. For the first time the concept of ‘window of opportunity’ began to be crystallized, according to which, if HRT is started soon after menopause, heart attack can actually be prevented.
Finally, after study of all accumulated data, the IMS and other organizations issued recommendations for HRT in 2007. According to these, HRT remains the best treatment of symptoms of menopause, prevention and treatment of osteoporosis, with benefits in joint and muscle pains, mood, sleep disorders and for improvement of quality of life of the postmenopausal woman. If started within 10 years of the last menstrual period, it may have cardiac benefits too. At least, it will do no cardiac harm. But HRT should neither be started nor continued after 60years age till further research comes in. There is short term benefit in cognition. Risk of Alzheimer’s disease decreases if started in the ‘window of opportunity’, symptoms also decrease but the progression is not halted. Effect of HRT on Parkinson’s disease is not known at present. Dementia and epilepsy, however, increase on HRT and it is not indicated for treatment of depression.
The word Hormone Therapy in menopause includes estrogen with or without progestrogen and Tibolone. By now it is reasonably clear that Estrogen and combined therapies have benefits more than the risks. Yet there are many women who desire an alternative therapy and, if possible, a better therapy. This is where Tibolone comes in.
Tibolone is a molecule which metabolizes in the body into 3 different by-products which have estrogenic, progestrogenic and androgenic actions on different target organs, thereby combining the best of estrogen/progesterone hormone replacement therapy. Tibolone is as good as estrogen for symptoms of menopause, but much better for anxiety, sleep, mood and excellent for libido because of its androgenic action. It helps in rebuilding the muscle mass lost during menopause and decreases total body fat. It has beneficial effects on the lipids, blood vessels and heart and is cardio-protective. It decreases the loss of bone density and prevents fractures as effectively as estrogen. It decreases the proliferation of breast cells and is ‘breast friendly’. Unlike estrogen, it also decreases breast density, which is considered a risk factor for breast cancer, and pain. This makes it an ideal hormone therapy for those who had breast cancer in the past and for those with a deep fear of breast cancer. Estrogen increases the chances of cancer of the uterus. Therefore in women with intact uterus, it should be combined with a progestrogen. Tibolone is not only safe for the uterus but has lower incidence of abnormal bleeding than estrogen which alarms many women. No wonder, discontinuation rates are lower with Tibolone. It can also be given to women with fibroids since it does not increase their size. Thus Tibolone combines many advantages of estrogen. Its safety profile and tolerability are better than estrogen. It is a heart friendly, bone friendly, breast safe and bleed free therapy. Unlike estrogen, however, its effects on the brain and nervous system are not totally clear at present.
Since life expectancy has increased, women now spend one-third of their life after menopause. Treatment of their acute problems and prevention of chronic diseases like heart disease and osteoporosis is imperative as well as improvement of their quality of life and the joy of living. With data available from current research, it is now possible to offer post-menopausal women a therapy of their choice.
By the end of 2002, the prescriptions for hormone therapy in menopausal women had completely stopped. The 2 mains issues responsible for this were fears of breast cancer and cardiac risks. These issues were addressed by several independent international societies devoted to the health of the menopausal women. The questions addressed were: Does HRT really cause breast cancer? Does HRT increase cardiac risks?
The conclusions of all of them were similar to the recommendations released by the International Menopause Society (IMS) after its conclave in Vienna in 2004.The 2 landmark trials which have influenced prescribing patterns over the last few years have been the WHI Trial 1 (2002, Estrogen + Progestrogen), WHI 2 (2004, Estrogen alone) and the Million Women Study, 2003. Both were found to have significant flaws. In WHI 1, breast cancer was ‘apparently’ increased because it was decreased in the control group. Therefore this was no ‘real’ increase. In WHI 2, breast cancer was 23% lower! The increase of breast cancer found in the MWS was only in the first year of use of HRT. It is possible that these were pre-existing cancers and HRT could not be held responsible for their occurrence.
For cardiac risks, 3 major studies were reanalyzed including the WHI Trial. It became very clear that increased cardiac risks were because the average age of the population studied was around 65 years. On the other hand, the NHS, which had found beneficial effects on the heart, had studied a much younger population who still had early symptoms of menopause. It is possible that the physiology of the early menopausal years is different from late menopause. The conclusion was that the results of the WHI can certainly not be generalized or extrapolated to populations it did not study. Therefore all conclusions drawn from this important study now became invalid. The fears about HRT began to recede and the pendulum began to swing back in favour of HRT. For the first time the concept of ‘window of opportunity’ began to be crystallized, according to which, if HRT is started soon after menopause, heart attack can actually be prevented.
Finally, after study of all accumulated data, the IMS and other organizations issued updated recommendations for HRT in 2007. According to these, HRT remains the best treatment of symptoms of menopause, prevention and treatment of osteoporosis, with benefits in joint and muscle pains, mood, sleep disorders and for improvement of quality of life of the postmenopausal woman. There is a definite difference between benefit, no harm and harm. At least, even if there is no benefit, HRT will do no cardiac harm, if started within the ‘window of opportunity’ period of first 10 years after menopause. But HRT should neither be started nor continued after 60 years age till further research comes in. There is short term benefit in cognition. Risk of Alzheimer’s disease decreases if started in the ‘window of opportunity’, symptoms also decrease but the progression is not halted. Effect of HRT on Parkinson’s disease is not known at present. Dementia and epilepsy, however, increase on HRT and it is not indicated for treatment of depression.
The word Hormone Therapy in menopause includes estrogen with or without progestrogen and Tibolone. By now it is reasonably clear that Estrogen and combined therapies have benefits more than the risks. Yet there are many women who desire an alternative therapy and, if possible, a better therapy. This is where Tibolone comes in.
Tibolone is a molecule which metabolizes in the body into 3 different by-products which have estrogenic, progestrogenic and androgenic actions on different organs, thereby combining the best of estrogen/progesterone hormone replacement therapy. Tibolone is as good as estrogen for symptoms of menopause, but much better for anxiety, sleep and mood and excellent for libido because of its androgenic action. It helps in rebuilding the muscle mass lost during menopause and decreases total body fat. It has beneficial effects on the lipids, blood vessels and heart and is cardio-protective. It decreases the loss of bone density and prevents fractures as effectively as estrogen. It decreases the proliferation of breast cells and is ‘breast friendly’. Unlike estrogen, it also decreases breast density, which is considered a risk factor for breast cancer, and pain. This makes it an ideal hormone therapy for those who had breast cancer in the past and for those with a deep fear of breast cancer. Estrogen increases the chances of cancer of the uterus. Therefore in women with intact uterus, it should be combined with a progestrogen. Tibolone is not only safe for the uterus but has lower incidence of abnormal bleeding than estrogen
which alarms many women. No wonder, discontinuation rates are lower with Tibolone. It can also be given to women with fibroids since it does not increase their size. Thus Tibolone combines many advantages of estrogen. Its safety profile and tolerability are better than estrogen. It is a heart friendly, bone friendly, breast safe and bleed free therapy. Unlike estrogen, however, its effects on the brain and nervous system are not totally clear at present.