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.

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