Microsoft word - overview of estrogen.doc


What is Estrogen?
Estrogen is a hormone that is primarily produced in the ovaries in three main forms: estrone
(E1), estradiol (E2), and estriol (E3). In human, the estrogens are primarily composed of 10-
20% estradiol (E2), 10-20% estrone (E1), and 60-80% estriol (E3)1.
Estradiol (E2 is the predominant estrogen produced in pre-menopausal women while estrone
(E1) is the primary estrogen produced after menopause. In the body, estradiol is reversibly
oxidized to estrone and both estradiol and estrone can be converted to estriol. The potency of
E2 is 12 times that of E1 and 80 times that of E32. A comprehensive review of the safety and
efficacy of estriol suggests that it may be safer than estrone or estradiol, but can still have a
stimulatory action on the endometrium and the breast when given in high doses3.
The benefits of Natural Estrogen Replacement:
In women, the primary functions of estrogen are to promote the development and maintenance
of female reproductive structures, particularly the endometrium, to ensure the development and
maintenance of female secondary sex characteristics. Estrogens can also reduce risk of
Alzheimer’s disease, cardiovascular disease, osteoporosis and arthritis. And last, but not least,
they can maintain the healthy skin, and eliminate vasomotor symptoms of menopause, such as
hot flashes and night sweats.
How is natural estrogen available?
Natural estrogens are made from soybeans. These estrogens can be used as a single agent or in
combination for replacement therapy due to menopause, ovarian failure or for women who have
had a hysterectomy with removal of their ovaries. They can be taken po, sublingual or dissolved
in the cheek pocket, rubbed into the skin, inserted vaginally or apply transdermally. The
advantage of the transdermal, vaginal or sublingual routes is that the dose can be lower than the
oral dose because there is no first pass effect by the liver. However, the disadvantages of
patches are skin irritation and sometimes they won’t stick, and the taste or time it takes to
dissolve a sublingual lozenges4.
Potential side effects of natural estrogen:
Estrogens’ side effects include: nausea, loss of appetite, breast tenderness, headaches and
alterations in body chemistry. The increased risk of cancer is also present. However, the concern
of cancer can be mediated by lowering the dose of estrogens and by adding progesterone.
All of the pros and cons of bio-identical estrogen should be discussed with patients before
starting the therapy4.
“Tri-est” and “Bi-est” formulations of natural estrogen:
According to Wright’s research5, a combination of three bioidentical estrogens found in triple-
estrogen or “Tri-est” formulation (estriol, 80%; estradiol, 10%; and estrone, 10%) would more
closely mimic the natural proportions of endogenous hormones and would maximize the
benefits of estrogen and minimize its risks6.
Bi-estrogen or “Bi-est” formulation (estriol, 80% to 90% and estradiol 10% to 20%) is another
popular estrogen combination used in compounding pharmacies. This double-estrogen therapy
is formulated based on the theory that because estradiol is 10 times more potent than estrone in
controlling vasomotor symptoms, estrone is not needed for efficacy, and removing it from the
formula may decrease the risk of breast cancer6.
Dosing of double-estrogen or triple-estrogen is generally in the range of 0.625 to 5 mg given once or twice daily, varied with the patient6. Since “Bi-est” and “Tri-est” formulations are less potent than conjugated equine estrogens (Premarin), a synthetic estrogen, the dosages of these bioidentical hormone combinations need to be higher6 (Table 1). Table 1. Estrogen Dosage Conversion Chart7
“Biest” and “Tri-est”

Please contact Costa Mesa Compounding Pharmacy for more information or questions on
prescribing a natural estrogen therapy. Our pharmacists are specially trained and assisted by the
Professional Compounding Centers of America (PCCA) to work closely with you to prescribe
every individualized formulation to meet the unique needs of your clients.

1. Allen L. Compounding for Hormone Replacement Therapy. Secundum Artem Current &
Practical Compounding Information for the Pharmacist. 8:1-5 2. Lorentzen J. Hormone Replacement Therapy: part 2 Estrogen Defined. IJPC 2001 Nov- 3. Moskowitz D. Changing Views: The emergence and efficacy of natural hormones in the treatment of menopause. JANA Fall 2000;3(3):36-44 4. Boomsma D. Natural Hormone Replacement Therapy. Williams apothecary. 5. Wright J. Comparative measurements of serum estriol, estradiol, and E1 in non-pregnant, premenopausal women; A preliminary investigation. Altern Med Rev 1999; 4:266-270 6. Wepfer S. Part 1. The science behind bioidentical hormone replacement therapy. IJPC 2001 7. Professional Compounding Centers of America, Inc (PCCA)-1-800-331-2498



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