The issue of Estrogen Replacement Therapy, (ERT), has become very controversial. In an attempt to apply a rational approach to the subject I will speak to the following topics:

Conditions that may be improved or be helped by ERT   Signs and Symptoms of Estrogen Excess   Who should consider ERT?   Who should avoid ERT?   The benefits and risks of combining Estrogen with Progesterone, (HRT)   Strategies to guide decision-making when you are not clear   Strategies to reduce the risk of cancer whether or not you are using hormones

In a general sense, there are no absolutes. ERT or HRT is not absolutely right or wrong for anyone. The type of hormone, the dose, the route of delivery, and the length of time for using hormone therapy must be individualized. Once a particular therapy is adopted it must be reevaluated at appropriate intervals. A therapy that is good for a woman during one time of her life may not be the correct therapy at another time. Our understanding of this complex subject is changing continuously due to our increasing experience and the regular availability of new scientific information.

Symptoms and Signs of Estrogen Deficiency:

The symptoms of hot flashes, night sweats and palpitations are actually due to rapid shifts in estrogen levels. That is why, as menopause progresses, these symptoms usually resolve. They can be terribly distracting while active. These symptoms can be improved with hormone therapy. Other strategies that may be effective for some women include the use of herbs such as Black Cohosh and Vitex, (chasteberry). Isoflavones from plant sources such as soy, red clover and other legumes may be effective in reducing these symptoms in some women. In the last two years, a series of studies evaluating these alternative strategies have not demonstrated a reliable benefit in terms of symptom relief.

Sleep loss due to the above-mentioned symptoms is common. This can lead to fatigue, brain fog, (muddled thinking), decreased memory and a lethargic depression. Since the brain has many estrogen receptors it is not clear whether these symptoms are due to a lack of sleep or a reduction of estrogen levels. I suspect that both factors contribute. The component of psychological and cognitive symptoms that are due to a lack of estrogen are generally not adequately addressed by herbal supplements or the use of soy products.

Gynecological symptoms include vaginal dryness, painful intercourse, frequent bladder infections, bladder irritability and urinary incontinence.

Signs and Symptoms of Estrogen Excess

Post-menopausal women who are not taking HRT do not experience these symptoms. It is worth knowing whether these symptoms were present before menopause. This information may help assess risk to hormone dependent cancer, (breast, uterus, and ovary) and guide your choice regarding HRT.
Psychological symptoms of Estrogen Excess include agitated depression, mood swings, hyperirritability, and anxiety.
Gynecological symptoms include fibrocystic breast problems, breast tenderness, abnormal uterine bleeding, and abnormal Pap smear.
General symptoms include fluid retention, bloating, weight gain, flushing of the face and headaches.

Who Should Strongly Consider Using Estrogen Replacement

• Women who are experiencing symptoms of estrogen deficiency that are severe enough to compromise quality of life
   

• Women with a strong family history of Alzheimers Disease and other forms of Dementia
   

• Women with evidence of bone thinning, (osteopenia), or significant bone loss, (osteoporosis)
  The value of HRT as regards Cardiovascular Disease, (heart attack), and Cerebrovascular Disease, (stroke), has become increasingly controversial. A recent analysis of the large studies done in Europe and the United States suggest that HRT begun around the time of the cessation of menstruation may actually be protective for cardiovascular disease. On the other hand, women who start HRT several years after the cessation of menstruation appear to be at increased risk of cardiovascular disease when they use Premarin, (a complex of estrogen molecules derived from horse urine) and a Progestin, (an artificial form of progesterone). Interestingly, the sub group of women who were not put on a Progestin, (they had a hysterectomy), did not have an increased risk of cardiovascular disease or breast cancer. It is clear that women with active cardiovascular problems should not receive HRT. This series of sentences speaks to the importance of individualizing recommendations for HRT.

Who should be wary of using Estrogen Replacement:

• Women who have had breast cancer

• Women with a close blood relative who have had breast cancer. The relative can be from the mother or fathers side of the family.

• Women who have had a blood clot

• Women who have active Cardiovascular or Cerebrovascular Disease

• A history of Gall Bladder Disease, Seizure Disorder, Liver Disease, and Migraine are relative contraindications to the use of HRT.

• There are multiple secondary risk factors for breast cancer such as:
  Years of menstruation; the more years the greater the risk

• Parity; having more than one child before age 30 will lower risk while having fewer children later in life will increase the risk

• Obesity will increase risk

• Alcohol use may increase risk

• A history of fibrocystic disease necessitating biopsy may increase risk

• A history of Estrogen Excess symptoms prior to menopause may increase risk, (see the material above)

The Benefits and Risks of Estrogen and Progesterone:

Articles published in medical journals recently have fanned the flames of concern and rightly so. Every woman must come to a decision, which she can live with, from a rational and emotional point of view. The difficulty with making a rational decision to use hormone replacement is aggravated by reporting in the lay press. These reports tend to exaggerate the risk and ignore the benefits of hormone replacement. The recent studies do suggest an increase risk for breast cancer in women using hormone replacement. The risk increase is greatest when estrogen and progesterone are used together in a cyclic fashion. The risk decreases when estrogen and progesterone are used continuously. The risk is still increased, but less so, when estrogen is used alone. The length of time one uses HRT is important. We do not see risk elevation to breast cancer until at least 5 years of replacement therapy. The incidence of breast cancer rises significantly after 10 years of replacement therapy.

The Nurses Health Study was published in the New England Journal of Medicine in 1997. They found a 37% reduction in all causes of mortality, (death). Death from heart disease was reduced by 53%. Death from stroke was reduced by 32%. Death from all types of cancer was reduced by 29%. This study suggested that HRT was safe, (in relationship to breast cancer), for 10 years, at which time the risk of death from breast cancer escalated to 43%.

Another study published recently reported that women using HRT with estrogen plus progestin, (the artificial form of progesterone), may have an increased risk of developing breast cancer of 38% after 5 years of HRT. The average risk of developing breast cancer in women between the ages of 50 to 60 is 2.4%. This means that between 2 and 3 women will develop breast cancer for every 100 women without HRT. A 38% increase in incidence with HRT means that the incidence will increase to 3.3%. That means that between 3 and 4 women will develop breast cancer after using HRT for 5 or more years.

On July 9, 2002 there was an announcement of findings concerning participants in the Women’s Health Initiative, (WHI). This was a large scale, randomized, controlled clinical trial. 16,608 menopausal women who were 50-79 years of age and who had an intact uterus received either HRT in the form of 0.625 mg of conjugated equine estrogens and a progestin, (artificial progesterone); 2.5 mgs of medroxyprogesterone acetate, (Prempro), or a placebo. Compared to the placebo group the HRT group experienced more strokes, heart attacks, blood clots, and an increase risk of invasive breast cancer. The study was stopped before its completion because of these findings.

The conclusions from this study were that there was a 29% increase in heart attacks. This means that per 10,000 person years, there would be 37 women who used hormone therapy compared with 30 women who used placebo who would have a heart attack. The study reports a 41% increase in strokes in the treatment group which means that there were 29 cases of stroke in the hormone group compared to 21 cases in the placebo group per 10,000 person-years.

Additional observations from these studies noted

• Women who took estrogen without the progestin, (artificial progesterone), did not have an increased incidence of breast cancer or heart attack when compared to the placebo group, (no HRT).
   

• Women who started HRT soon after menopause had protection for cardiovascular diseases over a 5 year period of observation.

I conclude that one can not rely on hormone therapy with estrogen from horses’ urine and artificial progesterone to provide protection from heart attack and stroke. In addition, we can conclude that every woman does not respond equally to the same therapy. We should individualize therapy based on the time of life, symptoms and secondary risk factors.

Many people wonder whether the type of hormonal products used can affect the outcomes. They suggest that the use of natural estrogen and progesterone would be safer and result in a lower incidence of cancer, cardiovascular disease and stroke. There are reasons to believe this may be so from the medical literature. In truth, there are no human studies to support this belief. I believe that the use of natural hormones is safer. When natural hormone use is combined with optimal diet and supplement regimens, I believe we are doing every thing we can to lower the risk of cancer with hormone use.

Strategies to Guide Decision Making

The benefits of HRT are constantly debated. The weight of the scientific evidence supports several ideas. All cause mortality is decreased with HRT. This means that women who use HRT live longer than women who do not. In addition use of HRT soon after the onset of menopause has favorable effects on risk to Alzheimers Disease, Cardiovascular Disease, Colon Cancer and Osteoporosis.

The magnitude of symptoms and the degree that the symptoms impair normal functioning is a very compelling issue during early menopause. In most cases, it is safe to use HRT for a limited time in order to relieve symptoms. This time should be individualized.

When considering the long-term health issues, I review the reasons for avoidance and weigh them against the possibility of benefit. In a patient with more than one risk factor for a chronic health problem that may benefit from HRT and no major risk factors for breast cancer, I will recommend HRT with natural hormones. In a patient with major risk factors for breast cancer I will seek to manage the symptoms and risk factors with alternative therapies, which might include diet, supplement, herbs and prescription medications.

Problem Specific Use of Hormone Therapy

There are many safe and effective strategies to address issues of Estrogen Deficiency as it applies to specific problems.

Systemic symptoms such as Mood Disturbance, Sleep Disturbance, Hot Flashes, and Night Sweats can be addressed with the safest form of estrogen known as Estriol. Estriol has one twentieth of the potency of Estradiol the commonly used form of estrogen in HRT. It does not stimulate the uterus and therefore has no association with an increased risk to uterine cancer. It does not stimulate the breast tissue. Therefore it does not cause symptoms of breast tenderness and swelling. There is no literature published suggesting that there is an increase in risk to breast cancer with its use. There is literature that suggests that adequacy of Estriol may be associated with a decreased risk to breast cancer. Estriol is the main form of HRT used in Japan where breast cancer incidence remains low. The dose is 2 mgs taken by mouth daily

I have had excellent results using Estriol with my patients. The dose range is 0.5-4 mgs given by mouth, applied to the skin or applied as a vaginal suppository. The dose is adjusted to provide control of disabling symptoms related to menopause. This is commonly used in other countries as a form of HRT. We have had excellent results with a dose as low as 0.5 mg of Estriol applied vaginally three times per week. This is equivalent to 1% of the dose of Premarin or Estradiol used in conventional Hormone Replacement Therapy.

Aesthetic Symptoms

The fine skin wrinkling that occurs around the eyes and the lips is associated with a decline in estrogen levels. There are many good articles in the medical literature showing that a low dose of Estriol applied as a cream will prevent and reverse wrinkling. When used in an appropriate concentration there is no significant systemic absorption.

Gynecological Symptoms

The dominant Gyn symptoms are vaginal dryness, an increase in urinary frequency, urinary incontinence and an increase in urinary tract infections. A health vaginal lining can alleviate or minimize these problems. We recommend a very low potency Estriol vaginal suppository with good effect. At times we will also recommend an intra vaginal testosterone suppository. This may be useful in building bone density and strengthening the muscles of the pelvic floor to help with symptoms of urinary frequency and incontinence.

Sexual Dysfunction

Sexual Dysfunction problems include low libido, vaginal dryness with painful intercourse, and a decrease in sexual response or pleasure. There are many non-hormonal causes for these problems including chronic diseases, relationship difficulties, depression and medication side effects.
When low libido has a hormonal cause it is most likely due to low anabolic/androgenic hormones.

These hormones include DHEA and Testosterone. When the levels of these hormones are low we can safely provide replacement therapy. Replacement doses vary and depend on follow up blood testing to achieve a dose that is optimal and safe. Replacement regimens can include oral, sublingual, transdermal and transvaginal delivery.

A reduction in the ability to achieve sexual response or experience pleasure can be addressed with strategies that improve clitoral blood flow and increase local tissue sensitivity. This may include the use of topical testosterone, topical vasodilating medications, (Viagra), and topical tissue sensitizers, (menthol).

Vaginal dryness can be addressed by the use of topical hormones, (Estriol), and other agents that increase vaginal lubrication, (vasoactive intestinal peptide).

The issue of prevention is relevant to women before and after menopause. It is relevant for menopausal women whether they use HRT or do not. The majority of cases of breast cancer in post menopausal women are not accounted for by the use of HRT. Avoiding HRT does not in any way provide assurance that breast cancer will not occur.

Please review the article on Strategies to Reduce the Risk of Hormonally related Cancer that is available on our website.