Female Hormone Restoration

How Bioidentical Estrogen-Progesterone Is Prescribed

Currently the commercial availability of individually tailored bioidentical hormone prescriptions is limited. As a result, many physicians utilize compounding pharmacies to dispense bioidentical hormone prescriptions for their patients. To obtain the phone number of a compounding pharmacist in your area, call 1-800-226-2370.

Most practitioners use the level of estradiol in the blood, in conjunction with an assessment of the patient’s clinical symptoms, to gauge the initial dose of bioidentical estrogen. The estradiol blood level must be considered in conjunction with of the levels other hormones, such as progesterone. A health care practitioner may also measure levels of estrone and estriol to obtain a more comprehensive assessment of a woman’s estrogen status.

A menopausal woman typically has an estradiol blood level of 0-19 pg/mL. With the use of bioidentical estrogen topical cream (e.g., compounded estriol and estradiol), the blood estradiol level may increase to 100 pg/mL or higher, which would indicate to the prescribing doctor that the compounded estrogen formula is being absorbed and has increased the patient’s estradiol to a more youthful level.

If the patient reports that her menopausal symptoms have been resolved, most practitioners would continue the current program and conduct periodic follow-up.

If, however, the patient is still having symptoms, the dose of bioidentical estrogen topical cream can be increased. In addition, further tests might be ordered. These could include a total estrogen blood test, or a urinary estrogen test to assess other estrogens and their associated metabolites. Based on the results of these tests, a more precise dose of estriol, estradiol, progesterone, and, occasionally, testosterone can be prescribed. A typical starting dose for bioidentical estrogen topical cream might read as follows:

Please note this is a general suggestion for an initial prescription. A physician experienced in bioidentical hormone replacement will tailor the prescription to the individual woman’s needs.

The bioidentical estrogen topical cream dose can be increased when severe symptoms of estrogen deficiency are present.

Women on an estrogen replacement regimen should also be prescribed natural progesterone (in contrast to synthetic progestin drugs like Provera®) in a dose that achieves a youthful balance. Natural progesterone produces many benefits when properly balanced with estrogen. The typical dose for topical progesterone cream may vary between 50-200 mg, depending upon a woman’s individual biochemical needs.

Typically, progesterone cream should be applied twice daily to different parts of the body. Specific dosing instructions are as follows:

• Premenstrual and perimenopausal women: 1/4 tsp. of a 2.5% progesterone topical cream (approximately 30 mg. natural progesterone) twice daily, starting on day 12 of the menstrual cycle continuing up to day 28.
• Menopausal women: 1/4 tsp. twice daily for 21 days, followed by 7 days off.

The dose can be adjusted up or down depending on a woman’s symptoms and her response to treatment. If using natural progesterone cream from a pharmacy, a prescription could be written as follows for a postmenopausal woman:

A prescription for a premenopausal woman might read:

Some physicians prescribe topical progesterone similarly to estrogens, i.e., in milligrams per fraction of a cubic centimeter (cc). These dosages are pressed out of a syringe onto the skin, and have the dual advantages of more precise dosage adjustment and smaller volume of cream, which is less likely to make a mess on clothing.

The blood level targets in aging women might be:

• Estradiol 90-250 pg/mL
• Progesterone 2.0-6.0 ng/mL
• Free testosterone 1.0-2.2 pg/mL

Before a prescription for bioidentical hormones can be written, it is important to have a baseline blood test so the doctor can determine the doses of bioidentical estrogens, progesterone, and possibly testosterone that might be needed. To order a comprehensive Female Blood Test Panel that includes estradiol, progesterone, and free testosterone, call 1-800-226-2370.

In order to achieve optimal hormonal balance, it is important to also address testosterone levels. Although testosterone is thought of as a male hormone, it plays an important role in women’s health as well. Testosterone levels decrease in women as they age. Low testosterone in postmenopausal women can have a negative impact upon sex drive, mood, psychological well-being, bone and muscle mass, and cardiovascular health (Ling 2009; Stuckey 2008; Maia 2009; Martin-Du Pan 2007). A physician experienced in bioidentical hormone therapy will measure testosterone levels in women and prescribe bioidentical testosterone if levels are low. Correcting low testosterone in women usually requires a 150-300 mcg patch or an individually prescribed testosterone cream (Davis 2008).

Since DHEA (dehydroepiandrosterone) can convert to testosterone in a woman’s body, a woman with low testosterone might be able to increase her testosterone level by taking 15 mg to 25 mg a day of DHEA, which is available as a low cost dietary supplement (Weiss 2009).

Phytoestrogens: An Alternative Option

Phytoestrogens are natural compounds found in some plants. They exert estrogen-like activity in the body and may be an effective alternative to bioidentical hormone replacement therapy for some women.

Some of the best evidence for phytoestrogens comes from Asia, where women do not typically experience many of the diseases and symptoms associated with menopause and the loss of estrogen. One explanation for this may be the phytoestrogens found in the soy and other plant products consumed in Asian diets (Aso 2010; Cho 2010; Sarkar 2003).

Phytoestrogens bind to estrogen receptors and help modulate estrogen activity (Zittermann 2003). When estrogen levels are too low, their very mild estrogenic effect raises total estrogenic activity. Alternatively, when estrogen levels are too high, they compete with estrogen at cellular receptor sites, thus reducing endogenous estrogenic impact. By competing with endogenous estrogen for estrogen receptors, phytoestrogens may help prevent the growth and spread of several hormone-dependent cancers (Adlercreutz 1992). They have also been shown to decrease the risk of some degenerative diseases, including cardiovascular disease, osteoporosis, breast and uterine cancer (Baber 2010; Bawa 2010; Cho 2010; Messina 2008; Miyake 2009).

Dietary and supplemental phytoestrogens present a way for women to obtain limited hormonal support without the use of hormones.

Cardiovascular Benefits: Unlike conventional HRT, which was shown to raise the risk of heart attack among postmenopausal women, phytoestrogens actually have a positive effect on the heart. In 1999 the United States Food and Drug Administration authorized the use of health claims on food labels that link increased soy consumption with a reduced risk of coronary artery disease (Vincent et al 2000). One study of more than 400 women demonstrated that phytoestrogens protect against arterial degeneration and atherosclerosis through their effect on the arterial walls, particularly in older women (van der Schouw et al 2002).

A review of scientific studies on phytoestrogens found they offer the following cardiovascular benefits:

• Improvements in lipid disturbances as a result of activating beneficial estrogen receptor sub-types (Okamura et al 2008)
• Decreased blood pressure, LDL cholesterol, total cholesterol, and triglycerides (De Kleijn et al 2002)
• Increased HDL cholesterol and improved cardiovascular profile (Bairey Merz et al 2006; De Kleijn et al 2002)
• Lowering of the overall rate of cardiovascular disease among people with higher consumption of phytoestrogens (Ariyo et al 2002)
• Lowering of lipids in people with high cholesterol via genistein and daidzein, two of the most extensively studied phytoestrogens (Teede et al 2001; Zittermann 2003)
• Reduction in the risk risk of atherosclerosis, due to increased levels of daidzein and genistein, which inhibit LDL oxidation (Exner et al 2001)

In addition, a six-month study of more than 180 women confirmed that a soy-rich diet is as effective as conventional HRT for lipid lowering (Park et al 2005).

Furthermore, phytoestrogens have up to almost 3 times the radical scavenging activity of vitamin C and vitamin E, and have protective effects on the arterial walls (Ruiz-Larrea et al 2000; van der Schouw et al 2002).

Brain protection: Estrogen and estrogen-like compounds protect brain cells from degenerative changes due to aging and oxidative stress (Bhavnani 2003; Linford et al 2002).

• The phytoestrogen genistein protects animal subjects from the effects of brain ischemia, the kind of injury seen in stroke (Schreihofer et al 2009; Donzelli et al 2010; Ma et al 2010).
• Genistein has anti-apoptotic activity, protecting cultured brain cells from self-destructing over time. (Yu et al 2009)

Osteoporosis and bone health: Studies have shown that postmenopausal women with a habitually high intake of phytoestrogens have high bone mineral density of the spine and hip (Bawa 2010; Hanna 2004). A number of studies have been conducted on phytoestrogens and bone health, and their conclusions are as follows:

• Genistein and daidzein increase bone mineralization (Taku 2010; Clifton-Bligh 2001; Kanno 2004).
• Genistein and daidzein decrease bone resorption and inflammatory factors and increase osteogenic (bone-forming) proteins (Ma 2008; Jia 2003; Rassi 2002; Yamaguchi 2000; Zhang 2004).
• An isoflavone mixture of daidzein and genistein demonstrated significant increases in bone mineral density after six months of treatment. Women who ingested 57 mg/day of isoflavones had a 4% increase in bone mineral density (Clifton-Bligh 2001).
• A phytoestrogen preparation containing daidzein and genistein demonstrated protective effects on the lumbar spine (Atkinson 2004).
• Dietary supplementation with 54 mg/day of genistein “may be as effective as hormone replacement therapy in attenuating menopause-related bone loss without causing the associated side effects.” (Cotter 2003)

Cancer Protection: Studies demonstrate a significantly lower incidence of sex-hormone–related cancer in Asian countries (Sarkar et al 2003; Vij et al 2004). These studies, which attribute this result to the traditionally high intake of soy isoflavonesin the Asian diet, have concluded the following:

• Daily soy isoflavone consumption is associated with decreased breast cancer risk (Lu et al 2001). A diet containing 113–202 mg/day (depending on body size) of genistein and daidzein can increase the production of the protective 2-hydroxylated estrogen, decrease estradiol and its harmful metabolites, and lower the long-term risk for breast cancer (Lu et al 2000).
• Genistein and daidzein also have an inhibitory effect on uterine cancer (Lian et al 2001).
• Genistein intake is also linked with lower rates of stomach cancer (Ko et al 2010).

Menopause symptoms: Several studies demonstrate that natural estrogens significantly decrease hot flashes and vaginal atrophy (Albert et al 2002; Chiechi et al 2003). Treatment with 54 mg/day of genistein safely decreases hot flashes up to 30% and should be considered as an alternative treatment for postmenopausal conditions (Crisafulli et al 2004). Subsequent studies showed a decrease in hot flushes of more than 56% (D'Anna et al 2009). A 2009 study concluded,“genistein can be used for the management of hot flushes in postmenopausal women not treated with hormone replacement therapy due to their superior efficacy to placebo and very good safety profile.” (Ferrari 2009)

Anticancer Nutrients to Complement Bioidentical HRT

Vitamin D confers significant protective effects against breast cancer. Women with higher vitamin D levels have a nearly 70% reduction in their risk of breast cancer compared to women with the lowest levels (Abbas 2008). Laboratory studies have shown that vitamin D suppresses growth of breast cancer by:

• blocking signals that stimulate cancer cell growth
• enhancing signals that inhibit cancer cell growth
• favorably altering genetic regulators of the cell cycle (Ben-Shoshan 2007; Lee 2007; Jamshidi 2008; Crew 2009)

The multi-faceted effects of vitamin D help prevent mutated cells from becoming malignant and even induce cancer cell death (apoptosis). Human studies show that daily doses of 1100 IU of vitamin D plus calcium result in a 60% risk reduction for developing any cancer, compared with placebo (Lappe 2007).

Cruciferous Vegetables, such as broccoli, cauliflower, cabbage, kale, and Brussels sprouts, can help detoxify dangerous estrogen breakdown products that promote cancer growth (Lampe 2009; Ambrosone 2004). When estrogens are metabolized via certain biochemical pathways, they become more likely to trigger cancer (Fowke 2006; Muti 2002). Aging adults suffer from a high prevalence of cancers associated with an imbalance in estrogen metabolism (Fowke 2006; Muti 2002). Cruciferous vegetables contain compounds that promote a healthier pathway for breaking down estrogen in the body, thus protecting against cancer (Muti 2000; Michnovicz 1997; Michnovicz 1998; Kall 1997; Bradlow 1996; Dalessandri 2004).

A chief component found in cruciferous vegetables, indole-3-carbinol (I3C), prevents conversion of estrogen to its breast-cancer-promoting 16-alpha-hydroxyestrone form, while increasing conversion to the cancer-fighting 2-hydroxyestrone form (Acharya 2010; Weng 2008; Muti 2000).

Lignans can slow down the growth of breast cancerin women. Thirty-two women awaiting surgery for breast cancer were randomized to receive a muffin containing 25 grams of flaxseeds or a muffin that did not contain flaxseed (control group). Analysis of the cancerous tissue after surgery revealed that markers of tumor growth were reduced by 30%-71% in the flaxseed group, while the control group did not experience any reduction in markers of tumor growth. (Thompson 2005).

A recently published study found that a combination of lignans, indole-3-carbinol, and calcium-d-dglucarate, along with other supportive herbs, favorably altered the 2/16-hydroxyestrone ratio in pre- and post-menopausal women. The researchers remarked, “Supplementation with a mixture of indole-3-carbinol and… lignan in women significantly increased estrogen C-2 hydroxylation. This may constitute a mechanism for the reduction of breast cancer risk as well as risk for other estrogen-related cancers.” (Laidlaw 2010)

A comprehensive review of 21 studies found that postmenopausal women with higher lignan intake were significantly less leikely to get breast cancer. The investigators concluded, “high lignan exposure may be associated with a reduced breast cancer risk in postmenopausal women.” (Buck 2010)

Fish oil, with its high omega-3 fatty acid content, reduces cancer risk by a number of mechanisms. Fish oil reduces oxidative stress and suppresses production of many inflammatory mediators that contribute to cancer development (Kansal et al 2010). It can sensitize tumor cells to chemotherapy effects, even when metastases are present, potentially reducing the doses of chemotherapy required for treatment (Bougnoux 2009).

A 2010 study revealed fish oil can prevent colon cancer progression through its effect on oxidative stress and induction of apoptosis (Sarotra 2010). In an animal model of breast cancer, fish oil supplementation was shown to reduce bone metastasis by blunting the expression of a protein called CD44, which drives cancer cell migration (Mandal 2010).

Green tea polyphenols, particularly one called EGCG, suppress growth and reproduction of human breast cancer cells and reduce the number of breast cancer tumors in animal models of the disease (Thangapazham 2007; Thangapazham 2007; Leong 2008). Green tea also reduces production of vascular endothelial growth factor (VEGF), helping to starve tumors of their blood supply, while down-regulating cancer-promoting estrogen receptors and increasing apoptosis (Leong 2008; Masuda 2002; Farabegoli 2007; Hsuuw 2007).

Pomegranate. Pomegranate has been extensively studied for its antioxidant properties as well as its cancer-fighting capacity. With respect to breast cancer, pomegranate is an especially promising phyto agent, because of its ability to both inhibit the cancer-promoting enzyme aromatase and suppress angiogenesis, which is the process by which tumors gain new blood vessels (Toi 2003; Sturgeon 2010).

Summary

Equine estrogens and synthetic progestins remained the staple of menopause care until 2002, when the Women’s Health Initiative revealed the dangers associated with these unnatural hormone replacement methods. As women learned that conventional hormone replacement therapy was closely tied to increased risks of certain cancers, many of them abandoned their trust in mainstream medicine and turned to natural bioidentical hormones and scientifically-validated phytoestrogens for menopausal symptom relief.

Emerging science continues to undermine conventional hormone replacement therapy in favor of bioidentical hormone replacement. Studies confirming the estrogen receptor modulating abilities of the natural estrogen estriol provide reassurance for women who seek relief from the ravages of age-related hormone loss but fear the increased cancer risks associated with equine estrogens and synthetic progestins.

By coupling healthy dietary and lifestyle habits with regular blood testing and bioidentical hormone replacement therapy, women today have a means to look and feel their best at any age.

Given the preponderance of evidence, maturing women should feel confident bioidentical hormone replacement, when appropriately prescribed, offers a safer and potentially even more effective alternative to conventional hormone replacement with non-bioidentical hormone drugs to help relieve menopausal symptoms and optimize long-term health. The addition of several proven nutrients to a bioidentical hormone regimen may help optimize estrogen metabolism and reduce cancer risk even further, offering an optimal, balanced approach to health maintenance.

Life Extension’s Female Hormone Restoration Recommendations

No program of hormone replacement should be launched without first undergoing a comprehensive female hormone profile blood test and a consultation with a qualified, knowledgeable physician. Once a baseline hormone profile is established, periodic blood testing is recommended to monitor hormone levels. Women interested in hormone blood testing can call 1-800-544-4440 or visit www.lef.org/blood.

Because each woman has a unique biochemistry and varying requirements, it is difficult to recommend a standard dose that would apply to everyone. Instead, Life Extension recommends that women rely on regular blood testing and strive for the following optimal hormone levels.