Hormones: Estrogen and Progesterone

Women and men have primarily three sex hormones: estrogen, progesterone and testosterone. Levels and ratios of these hormones differ between the sexes. Estrogen and progesterone are the dominant sex hormones in women whereas, testosterone is the predominant sex hormone in men. Understanding the interaction of estrogen, progesterone and testosterone is necessary to decipher symptoms and conditions caused by their imbalances.

"Estrogen" comes in three variations in the female body: Estrone (E1), Estradiol (E2), Estriol (E3). It is made in the ovaries, adrenal glands and fat cells. The scientific community often refers to all three forms collectively as "estrogen". However, each molecule has different actions and is present in different concentrations throughout a woman's life. Therefore, it is important to differentiate the three when referring to the "estrogen effects".

Estrone (E1) is the predominant form of estrogen in the postmenopausal period. It is manufactured in the fat cells primarily from androstenedione (a testosterone derivative). An increase in estrone correlates to increased body fat in the menopausal woman. Elevated estrone levels have been associated with increased incidence of breast tumors in animals.

Estradiol (E2) is the most active form of estrogen and is the predominant form of estrogen in women of reproductive age. Estradiol is made primarily by the ovaries and adrenals but is also made in small amounts by fat cells in the postmenopausal period.

Estriol (E3) is the weakest of the estrogens. It is primarily manufactured by the placenta during pregnancy. Estriol supplementation mainly affects the vaginal wall with little effect on the heart and bones. It also plays a role in hair, nail and skin health.

The scientific community often refers to all three forms (estrone, estradiol and estriol) collectively as "estrogen". However, each molecule has different actions. During the aging process, the ovaries cease to manufacture estradiol. The adrenal glands (small organs that sit onthe top surface of the kidneys) take over estrogen production in the form of estrone. The body transforms unused testosterone into primarily estrone and releases estrogen previously stored in fat cells.

Progesterone antagonizes the effects of estrogen, most importantly in the breast and uterus where it counteracts the stimulation of cell growth where overgrowth could lead to cancer. Progesterone is manufactured primarily by the corpus luteum on the ovary after monthly ovulation occurs and to a small degree by the adrenals. Progesterone is also manufactured by the placenta in great quantity during pregnancy. Progesterone is a precursor to most hormones making it extremely important far beyond the role it plays in the production of sex hormones.

For many reasons it is very important to maintain a healthy balance between these two sex hormones. Progesterone production diminishes significantly after menopause. Obese women who manufacture a significant amount of estrone in fat cells after menopause may not produce an adequate amount of progesterone, thereby increasing the likelihood of estrogen-related cancer, such as those of the uterus and breast.

More hormone discussion to follow...

Reference:
Schwartz ET, Holtorf K. Hormones in wellness and disease prevention: common practices, current state of the evidence, and questions of the future. Primary Care: Clinics in Office Practice 2008; 15(4)

Photomicrograph of estradiol crystals. Estradiol, the most potent of the natural estrogens, is used in its natural or semisynthetic form to treat menopausal symptoms.

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Lifestyle Changes Decrease Breast Cancer

The American Institute for Cancer Research/World Cancer Research Fund estimate that 40% of all breast cancers - over 70,000 breast cancer cases in the United States every year - could be avoided with simple lifestyle changes.

The update to the 2007 recommendations stem from review of 81 additional studies. The new AICR recommendations of lifestyle changes to decrease a woman's risk of breast cancer include:

1. Because of the link between excess body fat and cancer aiming to be as lean as possible without becoming underweight.
2. Physical activity for at least 30 minutes every day
3. If you drink alcohol at all, limit consumption to one drink per day.
4. Mothers should breastfeed exclusively for up to six months and then add other liquids and foods. Evidence is convincing that mothers who breastfeed reduce their risk for breast cancer. There is also probable evidence that children who are breastfed have a lower risk of gaining excess weight as they grow.

"This study represents the clearest picture we have ever had on how lifestyle affect's a woman's risk of breast cancer," declared Professor Martin Weisman, MD, Medical and Scientific advisor to the AICR and WCRF.

The AICR/WCRF report, Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective, was launched in November 2007 and is the most comprehensive report ever published on the link between cancer and lifestyle. For more information, visit http://www.dietandcancerreport.org/.

Bioidentical Hormones

Hormone therapy is a frequent topic of discussion with my patients. The media coverage of bioidentical hormones including Oprah, Suzanne Somers and Dr. Christiane Northrup have empowered women to seek a better quality of life and relief from menopausal symptoms such as hot flashes, night sweats, impaired sleep, vaginal dryness, decreased libido, painful intercourse, loss of memory and weight gain. This has caused quite a stir in the medical community. Why? Because women are asking questions they’ve not asked before – especially about bioidentical hormones.

What are bioidentical hormones? Bioidentical hormones are prescribed hormones that are identical to the hormones produced in a women’s body prior to the onset of menopause. The most commonly prescribed include three different types of estrogen (estrone, estradiol and estriol), progesterone, testosterone and dehydroepiandosterone (DHEA).

There are two categories of bioidentical hormones: compounded and manufactured.

Compounded bioidentical hormones are pills, creams, gels, suppositories, injectables, sublingual drops or lozenges that are prescribed by health care providers who tailor the dose to a woman’s individual symptoms and concerns. They are literally assembled in the pharmacy by a certified compounding pharmacist and are available through mail-order and some local pharmacies. Compounded bioidentical hormones are generally not covered by insurance and therefore are an out-of-pocket expense.

Manufactured bioidentical hormones are pills, creams, gels, sprays and injectable medications manufactured and marketed by large pharmaceutical companies. They come in standard doses and, therefore, are not available as tailor-made medications. There are other limitations with manufactured hormones. For instance, bioidentical estrogen is only manufactured as estradiol – the most potent of the three types manufactured in a woman’s body. Manufactured bioidentical hormones may be covered by insurance.

The alternative to bioidentical hormone therapy is synthetic hormone therapy. They include manufactured hormones that are similar to but intentionally different than the chemical structure as those hormones produced in a woman’s body. Premarin (conjugated equine estrogen) and Provera (a synthetic progestin) are the most commonly prescribed conventional hormones. They are the suspect hormones studied in the Women’s Health Initiative (WHI) Study that raised concerns about all hormone replacement therapy due to increased risks of blood clot formation, stroke, heart attack and cancer. Upon release of this information in 2002, many women abruptly stopped hormone usage and many physicians stopped or significantly limited prescribing hormone therapy.

The American College of Obstetricians and Gynecologist (ACOG) and the North American Menopause Society (NAMS) have recently issued statements supporting the use of manufactured bioidentical or conventional hormone therapy when necessary. They have also issued statements against compounded bioidentical hormones due to their unproven safety and efficacy.

The debate in the medical community continues regarding the safety and effectiveness of the bioidentical hormones as they have not been studied in large standardized controlled trials such as the WHI. However, it is difficult to undertake such studies when medications are tailor-made for individual women. Small European studies from the 1980’s suggest an improved safety profile with bioidentical hormones. However, this has yet to be proven.

A review article published in January of 2009 in the Journal of Postgraduate Medicine states that patients report greater satisfaction with bio-identical hormone therapies. Clinical outcomes and physiologic data support that bio-identical hormones are more effective than synthetic hormones and are associated with lower risks, including the risk of breast cancer, stroke and heart attack. Further randomized controlled trials are needed to further expound upon the differences.

References:

1. Holtorf K. The bioidentical hormone debate: are bioidentical hormones (estradiol, striol and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgraduate Medicine 2009:121(1). doi: 10.3810/pgm.2009.01.1949

2. Compounded bioidentical hormones. ACOG Committee Opinion No. 322. American College of Obstricians and Gynecologists. Obstet Gynecol 2005;106:1139-40.

3. North American Menopause Society Statement on Bioidentical Hormones Therapy

Effects of the Menopause Transition and Hormone Use on Cognitive Performance in Midlife Women

Many women come to me with complaints of impaired memory or "fuzzy thinking" during the peri-menopause (the period of time prior to the cessation of menses). As it turns out, until recently very few studies have been published assessing the change in cognitive function as women go through the menopausal transition. A study was published in the journal Neurology that evaluates the change in cognitive functioning women experience throughout the menopause transition and the effect hormone therapy has on altering the deterioration.

2,362 women between the ages of 42 and 53 were monitored for four years throughout their menopausal transition in the Study of Women's Health Across the Nation. Women were categorized into groups according to the time spent in the menopause transition, hormone use prior to the last menses and hormone therapy initiated after the last menstrual flow. Assessment of three types of cognitive functioning included processing speed, verbal memory and working memory.

The results were as follows:
1. Women do experience memory impairment (demonstrated as not being able to learn as well as during the pre-menopausal period) during the menopause transition
2. Once women were through the menopausal transition their memory impairment corrected to a pre-menopausal level suggesting the cognitive changes during the menopause transition are temporary
3. Women who took hormone therapy prior to their last menses had a beneficial effect on memory retention
4. Women who started hormone therapy after their final natural menses did not experience a beneficial effect and even proved to be detrimental their cognitive performance

In brief: cognitive function declined during the peri-menopause but hormone therapy started before a woman's last menstrual flow prevented the decline in function.

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Study Reference: Greendale GA, Huang M-H, Wight RG, et al. Effects of the menopause transition and hormone use on cognitive performance in midlife women. Neurology 2009;72:1850-7.

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Yoga Helps Reduce Hot Flashes

Some of the most life-altering symptoms of peri-menopause are hot flashes, night sweats, sleep disturbances and mental fogginess. Yoga is commonly recommended as a form of exercise for peri-menopausal women, but not necessarily for help with controlling peri-menopausal symptoms. A study recently published in the British Journal of Obstetrics and Gynecology suggests that women experiencing such symptoms could benefit from a regular integrated yoga practice.

Researchers conducted a randomized controlled study in 14 centers of yoga research in Bangalore, India to assess the effect of a regularly practiced yoga on peri-menopausal symptoms such as hot flashes, night sweats and sleep disturbance. They randomized 120 peri-menopausal women between the ages of 40 and 55 to either a yoga or control group. The women in the yoga group practiced yoga postures (asana), breathing exercises and cyclic meditation for one hour 5 days per week. The control group participated in supervised simple physical exercises for the same amount of time per week.

Results: The women in the yoga group experienced a greater reduction in hot flashes, night sweats and sleep disturbances. In addition, the women practicing yoga experienced improved cognitive functions such as concentration, memory (remote and short term) and an overall "mental balance".


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Reference: Chattha R, Nagarathna R, Padmalatha V, Nagendra HR. Effect of yoga on cognitive functions in climacteric syndrome: a randomised control study. BJOG 2008;115:991-1000