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Estrogen is a foundational hormone that regulates the brain and body bioenergetics in the female body.1 There are three types of estrogen found in a female body: estrone, estradiol, and estriol. The levels of all of these hormones fall dramatically at the onset of menopause. Estrogen is produced in a woman’s ovaries and adrenal glands. An extremely small amount of estrogen is produced in men through the conversion of testosterone. Symptoms characteristic of female menopause are hot flashes, insomnia, vaginal dryness, bladder problems, difficulty concentrating and anxiety.2,3 Unfortunately, health risks, including cardiovascular disease, stroke, osteoporosis, and Alzheimer’s disease, increase in the absence of estrogen.4-6

Rapid bone loss after menopause has been attributed to the decline in estrogen production, which is essential for bone growth. In addition, the loss of estrogen can result in the development of heart disease.7 Estrogen may lower total blood cholesterol and raise HDL (good cholesterol).8 And while estrogen protects the heart,5 it also protects the brain from cognitive impairments.6,9,10

There is no doubt that estrogen can protect a woman against many of the diseases of aging and that post-menopausal women on estrogen typically feel better and stay healthier. Unfortunately, most of the estrogen that is prescribed to women is synthetic estrogen, an estrogen that is not natural to the human body. Because of this, many women develop side effects. A healthy trend these days is to avoid synthetic estrogens and prescribe natural estrogens.11-13 Human receptor sites were designed to accept natural estrogen, not a synthetic form that can cause adverse symptoms. Studies have shown that long-term use of synthetic estrogens increases the formation of breast cancer.14  In contrast, natural estrogen, especially when taken in conjunction with natural progesterone, can protect against breast cancer similar to the way it protects against uterine cancer.15 In addition, the use of estriol, which is a weak estrogen, has been shown to lower the incidence of breast cancer.

Benefits of Estrogen Replacement

  • Protects against cardiovascular risks4,7,16
  • Supports healthy cholesterol8
  • Enhances memory and cognitive function6,9
  • Decreases symptoms of menopause17
  • Prevents bone loss by slowing down the process17,18
  • Improves vaginal dryness and eliminates bladder problems3,19

Side Effects

Side effects of estrogen therapy are often due to estrogen dominance, meaning no progesterone is providing a counter-balance or the progesterone level is too low compared to the amount of estrogen. Estrogen dominance can result in mood swings, depression, breast swelling, fibrocystic breast tissue, craving for sweets, sleep disturbances, uterine fibroids, weight gain, acne, and water retention.


Estrogen is best administered in the natural form as an estradiol or bi-est preparation. Estradiol is the most predominant estrogen in our body and the safest to replace. Bi-est contains estriol and estradiol and is supplied orally, transdermally or vaginally.


  1. Rettberg JR, Yao J, Brinton RD. Estrogen: A master regulator of bioenergetic systems in the brain and body. Front Neuroendocrinol. 2013 Aug 29. [Epub ahead of print] PubMed PMID: 23994581.
  2. Al-Azzawi F, Palacios S. Hormonal changes during menopause. Maturitas. 2009 Jun 20;63(2):135-7.
  3. Nappi RE, Lachowsky M. Menopause and sexuality: prevalence of symptoms and
    impact on quality of life. Maturitas. 2009 Jun 20;63(2):138-41. Epub 2009 May 21. Review. PubMed PMID: 19464129.
  4. Lobo RA. Benefits and risks of estrogen replacement therapy. Am J Obstet
    Gynecol. 1995 Sep;173(3 Pt 2):982-9.
  5. Masood DE, et al. Impact of sex hormone metabolism on the vascular effects of menopausal hormone therapy in cardiovascular disease. Curr Drug Metab. 2010 Oct;11(8):693-714.
  6. Yao J, Brinton RD. Estrogen regulation of mitochondrial bioenergetics:
    implications for prevention of Alzheimer’s disease. Adv Pharmacol.
  7. Kano H, et al. Estriol retards and stabilizes atherosclerosis through an NO-mediated system. Life Sci. 2002 May 24;71(1):31-42.
  8. Persson L, et al. Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women. Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):810-4.
  9. Rettberg JR, Yao J, Brinton RD. Estrogen: A master regulator of bioenergetic
    systems in the brain and body. Front Neuroendocrinol. 2013 Aug 29. [Epub ahead of print] PubMed PMID: 23994581.
  10. Yao J, Brinton RD. Estrogen regulation of mitochondrial bioenergetics:
    implications for prevention of Alzheimer’s disease. Adv Pharmacol.
  11. L’Hermite M. HRT optimization, using transdermal estradiol plus micronized
    progesterone, a safer HRT. Climacteric. 2013 Aug;16 Suppl 1:44-53.
  12. Mahmud K. Natural hormone therapy for menopause. Gynecol Endocrinol. 2010 Feb;26(2):81-5.
  13. Conaway E. Bioidentical hormones: an evidence-based review for primary care providers.J Am Osteopath Assoc. 2011 Mar;111(3):153-64.
  14. Beral V. Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003 Aug 9;362(9382):419-27.
  15. Holtorf K. The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgrad Med. 2009 Jan;121(1):73-85.
  16. Masood DE, Roach EC, Beauregard KG, Khalil RA. Impact of sex hormone metabolism on the vascular effects of menopausal hormone therapy in cardiovascular disease. Curr Drug Metab. 2010 Oct;11(8):693-714.
  17. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement therapy: scientific review. JAMA. 2002 Aug 21;288(7):872-81.
  18. Gambrell RD Jr. The women’s health initiative reports in perspective: facts or fallacies?Climacteric. 2004 Sep;7(3):225-8.
  19. Quinn SD, Domoney C. The effects of hormones on urinary incontinence in postmenopausal women. Climacteric. 2009 Apr;12(2):106-13.
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