How Hormone Therapy Can Slow Down Ageing – Part 3

Before embarking on hormone therapy of any description, it’s really important to understand all the risks. I know it’s a bit like a biology session, but I do recommend reading all the info so comprehensively laid out here by Dr Gordon. You will see that risks associated with BHRT are minimal compared to conventional hormone therapy, and in some instances is actually protective. It certainly hugely benefits the whole body at a stage of life when age starts to compromise general functioning.

I mentioned before that some BHRT can be got on the NHS. I’ve since discovered that it’s widely available, but due to the fact that it’s more expensive, it’s not generally known. You need to specifically ask your doctor for it. I think it’s really important to have a blood test for hormone levels both before and after embarking on the hormones to make sure the levels are correct. Problems can arise if the balance of the different hormones isn’t quite right. NHS doctors will not routinely offers these blood tests however, so it’s well worth mentioning any symptoms you have, as it might sway them to agree to the tests.

They will either offer a gel (good if your skin is efficient at absorbing it) or a pharmaceutical pill. Personally I prefer the compounded lozenges that I take, but they are only available privately from a compounding pharmacy. The reason being that the pills are processed through the liver which can have certain implications and the lozenges and creams bypass the liver and go straight into the blood which is safer. However, this is a more alternative view shared by myself and Dr Gordon. A more conventional doctor would probably not agree and would prescribe the pills.

 

Risks and benefits

This section is aimed at those who have a scientific or medical interest in bioidentical hormones and their risk-benefit profiles. It covers:

Oestrogen dominance

Breast cancer

Ovarian cancer

Blood clots

Heart attacks and strokes

Muscle, bone and connective tissue

Osteoporosis and bones

Please note that the spellings of the hormones change due to whether an American or English review has been summarised e.g. Oestrogen vs. Estrogen.

Oestrogen Dominance

Beginning in perimenopause and continuing throughout menopause, the production of progesterone tends to decline more rapidly than that of oestrogen. Progesterone imbalance can even be present in women in the teens and twenties.

Oestrogen dominance is often associated with the one or more symptoms:

• food cravings
• weight gain
• bloating
• breast discomfort and cystic changes
• fatigue
• mood swings, depression, irritability
• cyclical migraine and headaches
• skin changes
• hair loss or texture
• decreased sexual desire
• pms
• menstrual cramps, short or irregular cycles
• heavy menstrual bleeding
• growth of fibroids, and endometriosis

Factors contributing to oestrogen dominance include:

• Exposure to oestrogen-mimicking chemicals found in herbicides, pesticides, petrochemicals (e.g., BPA, bisphenol A) and PCB’s (polychlorinated biphenyl’s) used in some cosmetics, glue, plastic, and other modern materials (Tapiero 2002)

• Obesity due to increased intake of excess calories from simple sugars, fibre-deficient refined grains, trans-fats from partially hydrogenated vegetable oil
• HRT without bioidentical progesterone (Female Hormone Restoration 2013)

Replacing and balancing the oestrogen/progesterone levels in the body can be life changing. Nutrition, exercise and emotional balance help to balance oestrogen dominance.

Breast cancer

The next section reviews the research evidence on hormone treatment and breast cancer. It covers, the roles of oestrogen, progesterone, testosterone, and combinations of the three. The science and names can be confusing not only because of different spellings in the UK vs. US but also in the similarity of the names of the molecular structures. Persevere if interested.

The role of oestrogen

Breast cancer is more common after the menopause when oestrogen levels reduce.

There are 3 main oestrogens:

E1 Oestrone – E1 levels go up after the menopause. It is made from DHEA that originates in the adrenal. E1 has negative effects on the breast tissue; one theory is that E1 stimulates GPR30 receptors in breast tissue and encourages the cells to multiply. Nutritional focus on brassicas (plants in the mustard family ie. cabbage, broccoli etc) increases the amount of 2hydroxyoestrone, which protects the breast. (Female Hormone Restoration 2013)

E2 Oestradiol – E2 is the most active oestrogen and it is an essential aspect of BHRT. Oestradiol stimulates ER-α, an oestrogen receptor in breast tissue. Taken by mouth it is converted in the liver to other oestrogens that are less friendly to the breast, this does not apply to non-oral BHRT creams or lozenges.

Studies of women using non-oral BHRT oestradiol did not show any increase in breast cancer risk:

• A case-control study conducted in France amongst 1555 menopausal women demonstrated a significant increase in breast cancer risk in groups receiving oestrogen orally plus a synthetic progestin but no increased risk in those receiving oestrogen plus micronized bioidentical progesterone (odds ratio: 0.69-0.80, depending on duration of use).(Cook, 2014)
• Similar results were reported in the large French E3N cohort study of 80,377 women in postmenopausal women with a mean follow-up of 8.1 years. Compared to no HRT, oestrogen alone and estrogen plus a synthetic progestin (dydrogesterone or progestogen) yielded significantly increased risk for breast cancer, whereas the relative risk for oestrogen plus bioidentical progesterone did not increase and was 1.00 (95% CI: 0.82-1.22). (Cook, 2014)

E3 Oestriol -E3 is at its peak in pregnancy and is said to protect the breast tissue by inhibiting GPR30 receptors and stimulating ER-b receptors in breast tissue. Cancer of the breast is rare in pregnancy and women who have many children have a lower incidence of breast cancer.

BHRT uses an oestrogen combination called Biest containing Oestradiol E2 (20%) and Oestriol E3 (80%) and in theory this will protect and reduce breast cancer risk. There have been few case small controlled studies of Biest to date to confirm this.

Further research evidence on E1, E2 and E3 is shown in the box below. It is taken from an American publication hence the different spelling of the hormone.

The role of progesterone

Conventional HRT containing progestins increases the risk of developing breast cancer by 26%. (Chlebowski RT et al 2012)

The most compelling research comparing the breast cancer risk of BHRT to that of conventional HRT, suggests that the addition of bioidentical progesterone to oestrogen therapy does not increase the breast cancer risk.

The additional beneficial effect of bioidentical progesterone compared to non-bioidentical progestin includes fewer sleep problems, less anxiety and depression, less menstrual bleeding, fewer cognitive difficulties, and improved sexual function.

The role of testosterone

Testosterone does not increase breast cancer incidence in post- menopausal women. It also reduces breast cancer growth in animal models (Arumugam A 2014)

BHRT – A combination of hormones:

Treatment frequently uses combinations of Biest (oestradiol and oestriol), progesterone and testosterone.
In animal models of mice with breast cancer a BHRT combination, in optimal doses, inhibited the rate of growth of mouse breast tumours. The mouse tumours grew more slowly on the BHRT than when oestrogen blood levels were reduced in the mice using an aromatase enzyme inhibitor. This is a surprising finding and begs the question of how to treat women with breast cancer. (Arumugam A 2014)

Survival and quality of life:

Hormones have myriad effects throughout the body, effects that influence survival and quality of life as much as breast cancer recurrence does or more. A radical hypothesis: could an optimal choice of hormones lead to improved survival factors and quality of life enough to outweigh any negative effect on tumour recurrence? This suggests (though not yet proven) that other factors may be more important in preventing the recurrence of breast cancer than blocking oestrogen. (Arumugam A 2014)

Ovarian cancer

A recent review looked at 52 previous studies and found a statistically higher risk of ovarian in current HRT users of ovarian cancer. The risk in context; for every 1,000 women using conventional HRT for five years, there will be one additional ovarian cancer diagnosis and one additional ovarian cancer death for every 1,700 users. (Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies.2015)

This review did not distinguish between BHRT and conventional HRT. It is likely that the risk will be lower on BHRT.

Blood clots (thromboembolic risk)

Oestrogen pills (absorbed in the stomach) stimulate the liver to synthesise inflammatory compounds, including C-reactive protein, insulin-like growth factor, and clotting factors—factors associated with increased thromboembolic risk. Bioidentical oestrogens taken as creams or lozenges do not have the same effect and are safer than pills taken by mouth.

• The Million Women Study, in which more than 1 million women were followed for a mean of 3.1 years, demonstrated that current use of oral but not transdermal estrogen therapy increased the risk of venous thromboembolism (relative risk: 1.42 [95% CI: 1.22-1.66] vs. 0.82 [95% CI: 0.64-1.06]). (Cook,2014)
• Data from a recent 3-year study in 75 women given transdermal compounded BHRT (Biest, progesterone, testosterone, and/or DHEA) produced no thrombotic potential and favourable changes in inflammatory and immune markers (Cook,2014)
• The Estrogen and Thromboembolism Risk (ESTHER) Study, a multicentre case-control study demonstrated an increased risk of venous thromboembolism with oral but not transdermal use of estrogen and a 4-fold increased risk of myocardial infarction (MI) associated with oral estrogen compared to transdermal estradiol therapy. (Cook,2014)
• The ESTHER study also demonstrated that micronized bioidentical progesterone had no thrombogenic effect, whereas progestins (norpregnane) resulted in an almost 4-fold increase in thrombogenic events.

Heart attacks and strokes (CVD)

According to the Center for Disease Control, heart disease is the leading killer of American women. The risk for postmenopausal women is equal to that seen in men.

Menopause can be associated with elevations in blood pressure, lipids (low-density lipoprotein (LDL) cholesterol and triglycerides), as well as homocysteine levels, C-reactive protein, and interleukin-6 (an inflammatory cytokine). At the same time, high-density lipoprotein (HDL) cholesterol levels drop significantly. All of these changes are associated with oestrogen deficiency and an increased risk of CVD. Oestrogen is important for maintaining the integrity of the blood vessel endothelium, where atherosclerotic changes begin. (Cook,2014)

The role of oestrogen

• Large observational studies suggest oestrogens have a cardio-protective effect. Abnormal serum lipid levels have been associated with an increased risk for CVDs. Several clinical and experimental studies indicate that oestradiol treatment is beneficial to the heart by reducing LDL cholesterol levels and increasing HDL cholesterol levels (Cook, 2014)
• Oestrogen dilates the arteries and this protects the cardiovascular system.
• Serum concentrations of oestrogen are inversely associated with CVD risk (Arumugam 2014)
• Oestrogen replacement therapy initiated within 5 years after menopause has a beneficial effect on cardiovascular risk factors. Natural bioidentical hormone 17-b estradiol was more effective in reducing CVD risk factors than Premarin (conjugated equine estrogens). An oral or transdermal route of delivery (using creams of lozenges) leads to a more favourable outcome. (Cook,2014)

The role of progesterone and progestin

• Progesterone in BHRT is cardio-protective. The LDL Cholesterol is not increased and it does not alter the beneficial effect of oestrogen on HDL. (Arumugam A 2014)
• Progestins however raise LDL and lower HDL so the heart attack and stroke risk is increased.

The role of testosterone

• Testosterone reduces triglycerides, dilates blood vessels and does not raise LDL. It is cardio protective.

Muscle, bone and connective tissue

Muscle, bone and connective tissue are all derived from the same cells in the foetus, the mesoderm.

Factors that influence one of these affect them all.

Osteoporosis and bones

Osteoporosis is a major concern in postmenopausal women. The incidence increases progressively with age. BHRT can prevent or reduce bone loss and preserve the strength of skeleton. (Cook, 2014)

The role of oestrogen

• Oestradiol increases bone formation. Women taking BHRT usually have oestradiol blood levels checked to ensure it is absorbed and can therefore be effective on the bone.
• Biest, an oestrogen combination used for BHRT consists of oestradiol and oestriol. Oestriol also has a bone sparing effect. (Cook, 2014)

The role of progesterone

• Progesterone has a bone sparing effect.
• Several animal and human studies have demonstrated progesterone’s positive effect on bone formation by stimulating the osteoblasts that lay down bone and it reduces bone resorption. (Cook, 2014)
• Studies evaluating estrogen and progesterone supplementation suggest estrogen and progesterone have distinct but complementary roles in bone maintenance (Arumugam A, 2014)

The role of testosterone

• Testosterone has a bone sparing effect. The addition of testosterone positively influences bone mass by stimulating the osteoblast function. (Cook, 2014)
• Clinical trials on the effect of testosterone on BMD in women are limited but in theory testosterone has the potential to improve the effect of oestrogen in women using BHRT. Hormone balance in women includes testosterone.

BHRT combinations

• With BHRT oestrogen, progesterone and testosterone are frequently used in combination and the overall effect on the bone is likely to be greater though minimal data is available.
• All 3 hormones stimulate osteoblasts the cells that lay down the bone matrix and calcium.

The role of DHEA (Dehydroepiandrosterone)

• DHEA is a precursor hormone that converts into testosterone and oestrogen. DHEA is often used to improve energy. It probably inhibits osteoclasts, the cells that resorb bone and low levels of DHEA correlate with bone loss. DHEA supplementation may benefit the skeleton although the research information is minimal. (Cook, 2014)

The role of Vitamin D and other vitamins, minerals and Omega essential fatty acids

• Vitamin D aids the transport of calcium and is essential to bone health. (Cook,2014) Other vitamins and minerals contribute together with Omega 3 and other Essential Fatty acids.

The role of exercise

• Loading the bone stimulates the osteoblasts to lay down new matrix, incorporating calcium and strengthens the bone. (Cook, 2014)

Muscle, sarcopenia and physical activity

Muscle mass and size tends to diminish after the age of 55, the medical term is sarcopenia and by the age of 80 over 30% of women have this. It is now termed the Frailty Syndrome.

Sarcopenia results in fewer muscle fibres and the fibres are thinner. There are a number of reasons this could occur: underuse and under exercise (use it or lose it); reduced vitamin, mineral and protein intake, low levels of hormones (testosterone, oestrogen, possibly progesterone and growth hormone). It occurs more frequently in some families, there may be a genetic component. (Narrici M 2015)

BHRT combining oestrogen, progesterone and testosterone has been shown to improve muscle function. (Arumugam A 2014)

The best treatment for bone and muscle is prevention; it’s never too late to begin

Begin BHRT soon after menopause

The important hormones are

• Thyroid
• Testosterone
• DHEA
• Oestrogen and progesterone

Hormones are best applied as creams or lozenges

Help the hormones and muscles with the way you exercise and the way you eat

Skin, hair and connective tissue

Loose connective tissue is present in every organ of the body and forms a mesh that joins all the organs. Within the mesh are cells called fibroblasts and they form connective tissue fibres and between the fibres is a gelatinous fluid. This fluid is in balance with the fluid in the blood stream. The fibroblasts and the connective tissue fluid are sensitive to oestrogen, progesterone and testosterone hormones. Connective tissue is also sensitive to thyroid hormones and adrenal hormones (cortisol and aldosterone).

Hormonal balance

Hormonal balance results in skin and connective tissue health. Low levels of oestrogen results in a thin wrinkled skin. Oestrogen dominance with low progesterone causes swelling and oedema. Underactive thyroid or excess cortisol results in fluid retention and bloated connective tissue.

The fluid in connective tissue contains the same hormones as are in the blood stream. The connective tissue cells (fibroblasts) are also stimulated by oestrogen or progesterone or testosterone hormones.

One reason that facial skin “shrivels” as we age is that our natural hormone production markedly declines. To make matters worse, blood microcirculation to our skin is reduced as we grow older, thereby depriving our skin of the small amount of natural hormones. Oestrogen, progesterone and testosterone exert potent anti-aging effects on the skin of increasing thickness and moisture.

Muscle and bone and connective tissue all function best when the following are optimal and/or within the normal ranges when measured:

• Vitamins including vitamin D levels
• Minerals including iron, magnesium, chromium and calcium
• Essential fatty acids particularly Omega 3 (fish oil)
• Protein intake is regular
• Aerobic exercise is part of everyday life as it ensures blood and fluid flow and removal of waste substances thus promoting metabolism
• Stretching muscles and connective tissue is important to achieve and maintain flexibility
• Adequate rest to recuperate and rebuild cells

• Hormonal environment is measured and corrected
• Thyroid balance
• Cortisol adrenal balance
• Oestrogen, progesterone and testosterone levels are balanced (no oestrogen dominance)
• DHEA levels are optimal

Healthy looking skin and strong muscles and bones are the potential results of attention to these interventions.