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HRT with Cardiovascular and Breast Cancer Risk Reduction | OMICS International
ISSN: 2329-9126
Journal of General Practice
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HRT with Cardiovascular and Breast Cancer Risk Reduction

Khalid Mahmud*
Medical Director, Innovative Directions in Health, USA
Corresponding Author : Khalid Mahmud, MD
FACP, Medical Director
Innovative Directions in Health
7550 France Avenue S., Suite 215
Edina, MN 55435 USA
Tel: 952-922-2345
Fax: 952-922-1309
E-mail: [email protected]
Received August 13, 2013; Accepted November 01, 2013; Published November 07, 2013
Citation: Mahmud K (2013) HRT with Cardiovascular and Breast Cancer Risk Reduction. J Gen Pract 1:131. doi:10.4172/2329-9126.1000131
Copyright: © 2013 Mahmud K. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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The Women’s Health Initiative [WHI] study ended in 2002 because of the adverse effects of Premarin and Provera, including cardiovascular events [heart attack, stroke and pulmonary embolism] which affected 7% of the participants, and almost doubling the risk of breast cancer and mammographic abnormalities. It led to a major reduction in the use of hormone therapy for menopausal women, with significant consequences in terms of quality of life and possibly overall health. The following is a report of 460 menopausal women, who were administered multiple hormones, according to a rationalized approach described below. All patients received bio-identical estrogen and progesterone; 227 and 349 received testosterone and DHEA, respectively for suboptimal levels; 103 received thyroid replacement, and 89 received a growth hormone secretagogue for suboptimal Insulin like Growth factor [IGF]. No patient developed any cardiovascular complications over an average duration of four years. Premarin and Provera would have resulted in 33 such events. There were no hormone related breast cancers and no increase in mammographic abnormalities. In fact, eight abnormal [dense/cystic] mammograms showed improvement on follow up. There is a need to look into fresh approaches that could improve the quality and possibly quantity of menopausal years.

Hormones; Menopause; Heart attack; Stroke; Pulmonary embolism; Cardiovascular diseases; Breast cancer; Mammograms; Hormone therapy; Women’s health
Traditional hormone replacement therapy [HRT] consists of artificial estrogen [Premarin] and progesterone [medroxyprogesterone], and, as reported in the Women’s Health Initiative [WHI] studies, results in increased cardiovascular events, breast cancer and overall death rate [1-3]. Premarin and Provera are chemically different from endogenous hormones and are administered orally, unlike natural hormones which enter the blood stream directly. Natural estrogen and progesterone, identical to endogenous hormones, can be mixed by compounding pharmacies upon physicians orders, and can be given via natural routes [transdermal, vaginal, sub-lingual], avoiding unwanted first-pass liver effects. They can be optimally controlled by blood level monitoring, which is not the case with Premarin and Provera. Menopausal hormone deficiencies involve: estrogen and progesterone in all women. What is frequently not appreciated is the fact that many of them are also deficient in testosterone and DHEA, and some in thyroid and human growth hormone. All of these hormones have important functions in the body and should be considered for appropriate replacement.
The following is a report of 460 women who sought care for menopausal symptoms in a private clinic. They were treated with natural estrogen and progesterone and, when deficient, with testosterone, DHEA, thyroid and a growth hormone secretagogue, according to a rationalized approach described below. In addition to the symptomatic therapeutic effects, patients were monitored for complications, for an average follow up of four years. A complete absence of cardiovascular events, mammographic abnormalities, and hormone related breast cancer, is the subject of this report.
Patients and Methods
Patients [age 34-78, average 54.2] receiving management for menopausal symptoms in a private clinic setting were analyzed. Since WHI study had revealed a peak incidence of cardiovascular complications at 12 months, only 460 who had received therapy for one or more years [16-90 months, average four years] are included for this report. Of these patients 273 had gained weight during menopause, and 245 had other conventional cardiovascular risk factors including hypertension, hyper lipidemia, high CRP, and insulin resistance alone or in various combinations. In other words, no one had been excluded because of cardiac risk factors. Besides, four patients had a history of atrial fibrillation, one had frequent premature beats, two had known coronary artery plaque, one had had carotid surgery and two had had a previous heart attack.
All patients had decreased levels of estrogen [average 16 pg/ml] and progesterone [average 0.35 ng/ml] compared to premenopausal women; 227 had low/suboptimal testosterone [less than 18 ng/dl. Lab reference range 8-60], and 349 had suboptimal DHEA levels [less than 100 mcg/ dl. Lab reference range 45-430]. One hundred and three women were hypothyroid based on clinical symptoms [cold intolerance, fatigability, constipation, etc.] plus lab findings [TSH higher than 2, and free T3 lower than 2.6]. Eighty nine women had suboptimal growth hormone [IGF level of 100 ng/ml or less. Reference range 87-238].
All patients received estrogen and progesterone. Estrogen was administered transdermally as Biest cream [estradiol 1 mg+estriol 4 mg/gm]. Estriol was included because it has been described to reduce risk of breast cancer [4]. Transdermal application was chosen because it does not cause hyper-coagulability and high CRP associated with oral estrogens [5]. Also, it allowed for easy adjustment of dose according to symptom control and blood levels. Patients were generally started on ½ gm daily and asked to adjust upwards to control hot flashes and downwards if there was any breast tenderness. Blood levels were followed and maintained between 30-50 pg/ml-a low follicular level for younger women. Higher levels were avoided to prevent breast tissue stimulation. Twenty five women could not use transdermal cream for various reasons, such as irritation or poor absorption, and were switched the sublingual route.
Progesterone was administered as a sub-lingual triturate [50-100 mg] to achieve direct absorption into the blood stream, avoiding extensive first-pass hepatic metabolism of orally given progesterone. Blood levels were maintained around 4 ng/ml or somewhat higher because of a reported anti-breast cancer effect at this level [6]. Forty nine women were unable to take the triturate because of taste or difficulty absorbing and were switched to a 20% dermal cream using 1 gm/day as starting dose.
Testosterone was given to 227 women with diminished libido and low to low normal serum levels. It was used as a vanishing peri-vaginal cream around 3 nights a week, resulting in improvement in libido and dryness. Blood levels were monitored and maintained around 25 ng/dl, avoiding higher levels which could increase estrogen levels.
DHEA was administered orally to 349 women with low to low normal DHEA blood levels. The starting dose was generally 10 mg/day, and was adjusted to achieve a blood level around 120 microgram/dl, again a modest level for premenopausal women.
Of the 103 hypothyroid patients, 86 were treated with Armour thyroid and 17 with synthroid. Armour was preferred to supply T3 directly rather than hoping for adequate conversion of T4 [synthroid] to T3 in the body. Patients were monitored to control symptoms of hypothyroidism and to maintain free T3 levels between 3 -4 pg/mL, as “low T3 syndrome” [free T3 less than 3.1] has been described to result in up to five times increase in death rate in cardiac patients [7].
Eighty nine women with suboptimal growth hormone secretion, IGF level below 100 [normal range 87-238 ng/ml] received a predominantly arginine/lysine based secretagogue [GH Advantage, by Health Freedom Nutrition]five nights a week, which resulted in an average increase of 31% in IGF levels.
Three hundred and sixty five women had mammograms done by family physicians prior to enrolling with our program. Sixty eight [18.6%] had base line abnormalities such as fibronodular or cystic changes. They were asked to have follow up mammograms while on our program. Two hundred and ninty two had these follow up mammograms.
Pre-existing hypertension and hyperlipidemia were mostly under management by patients family physicians.
In addition to symptomatic improvement which occurred in 97% of the patients [the subject of a different report], patients were monitored for complications including cardiovascular events, breast cancer and mammographic abnormalities.
According to WHI trial, of the 8506 women receiving Premarin plus Provera 286 [3.36%] had a heart attack, 212 [2.5%] had a stroke and 112 [1.2%] pulmonary embolism, for a total rate of 7.06% cardiovascular complications [7]. Such therapy in our 460 patients would have resulted in 34 cases of these complications. We had none.
Three of our patients with strong family history of breast cancer, developed estrogen/progesterone receptor negative tumors. There was no hormone related breast cancer. In the WHI trial estrogen plus progestin almost doubled the mammographic abnormalities among participants. Among the 292 patients who had follow up mammograms in our program, no one developed a new abnormality. Instead, eight patients had an improvement in previous abnormality.
Aside from the WHI findings, there is evidence that natural estrogen and progesterone are cardio-protective. Mendelsohn [Molecular Cardiology Research Institute, New England Medical Center, Tufts University] has described cardiac effects of estrogen to include: induction of nitric oxide synthase, improvement in lipoprotein and triglyceride profiles, expression of coagulant and fibrinolytic proteins, and a favorable change in the expression of genes modulating response to injury and atherosclerosis [8]. Estradiol has been shown to reverse drug induced coronary spasm in women with coronary artery disease [9]. A large national study of Danish women has revealed a reduced risk of myocardial infarction in women receiving dermal estrogen compared to women not receiving any hormones, RR 0.62, P 0.04 [10].
Natural progesterone prevents coronary artery hyperactivity in animal studies [11]. It has been demonstrated to enhance the beneficial effect of estrogen on exercise induced myocardial ischemia in menopausal women, whereas medroxyprogesterone negates this benefit [12]. Medroxyprogesterone has actually been demonstrated to cause endothelial damage even in young women [13].
Testosterone, in small doses, was applied mainly to improve libido when diminished and not intended to improved cardiovascular function. However, a recent study has demonstrated improvement in heart failure in women [14].
In women with suboptimal levels, DHEA in small doses was included for its overall healthful effects. Again, a recent study points to increased cardiovascular mortality in women with low DHEA [15].
As mentioned above, low T3 syndrome has been associated with increase cardiovascular mortality. The importance of normal thyroid is the subject of many reports and well summarized in a recent editorial in the journal of Clinical Endocrinology and Metabolism [16].
IGF [insulin like growth factor] representing secretion of human growth hormone declines with aging. Human growth hormone has multiple functions in the body, including skeletal and cardiac muscle health. The cardiac benefits of growth hormone are the subject of many reports in the literature [17-19]. In patients with low IGF, it appeared reasonable to increase it modestly with a secretagogue, without having to use growth hormone injections.
Because estrogen is known to stimulate breast tissue, minimal doses with relatively low blood levels, enough to decrease hot flashes were preferred. On the other hand progesterone levels were increase substantially as mentioned above. Women with low progesterone levels have been reported to suffer a ten times higher cancer death rate than those with normal levels [20].
Since the publication of WHI reports, there has been a considerable drop in the use of hormone therapy for menopausal women. The PremPro results should not be extrapolated to all forms of hormone therapy. Our results suggest that a natural administration of all deficient hormones [bio-identically] with appropriate monitoring designed to improve quality of life, can also avoid cardiovascular events, breast cancer or mammographic abnormalities. Larger, controlled studies of such approaches need to be undertaken to find ways to improve the quality and quantity of menopausal years.
Conflict of Interest Statement
The author reports no conflicts of interest. No outside material or financial support has been received.

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