Oestrogen- Villain or Heroine?

I wrote this article for a local medical publication recently. Most women would be unaware of these facts.

Oestogen- Villain or Heroine?

Many of my patients express concern about taking oestrogen (E2), as it is firmly fixed in their minds that it causes Breast Cancer. After all, the breast has cancers that are E2- receptor positive. Does that not say it all? However, it is not that simple (it never is).

Quality of Life: E2 increased feeling of well-being in several trials[1],[2]. It also showed an improvement in Health related QOL in symptomatic women though an alleviation of symptoms[3].

Longevity: The Leisure World Cohort study[4] found that long term E2 users had a reduction in death from all causes of 15%. They state that “results of recent clinical trials and other observational studies, suggest that after an initial period of increased risk, the use of E2 therapy may be without excess adverse effect.”

Alzheimer’s disease: The Cache County memory Study[5] concluded that taking E2 use for more than 10 years reduced the risk of Alzheimer’s disease, if treatment commences at the onset of menopause. Another study found an enduring protective role of endogenous and exogenous E2 on memory in older postmenopausal women[6].

Colon Cancer: What is often forgotten is the proven reduction in colon cancer in women on HRT of 33%[7],[8],[9]

Heart disease: A study in the BMJ showed a significant reduction in mortality, heart failure and myocardial infarction in women on HRT for over 10 years[10]. Keep in mind that 50% of women over 50 will die of heart disease. This is over 7 ½ times the number that fall victim to breast cancer[11]. Further studies show that if women have HRT initiated within 6 years of menopause, they have a reduction of myocardial ischaemia and hypertension of 40-60%[12],[13],[14]

Osteoporosis:  Every study confirms that E2 are the most effective way of increasing bone density and preventing osteoporotic fractures[15],[16],[17]. It is more effective and beneficial than the biphosphonates that are frequently used by bone physicians as first choice and by GP’s unsure about the safety of E2 therapy, according to Professor Studd. Furthermore, studies from several centres have shown conclusively that E2 prevent collagen from being lost from the intervertebral discs thus maintaining their strength and function. This important protective effect of E2 seems to be unique as biphosphonates and the other non-hormonal treatments of low bone density do not have beneficial effects on the discs.

Depression: There are certain types of depression in women that are effectively treatable with E2, although psychiatrists seem to have closed their minds to this possibility to an extent which becomes dangerous for women[18]. Transdermal E2 and serotonergic and noradrenergic antidepressants are efficacious in the treatment of depression and vasomotor symptoms in symptomatic, midlife women[19]. Transition to menopause and its changing hormonal milieu are strongly associated with new onset of depressed mood among women with no history of depression[20],[21].

Libido: E2 certainly improves libido by helping vaginal dryness and painful intercourse. Even without these characteristic symptoms, estrogens can improve sexual desire[22],[23],[24]

Hair skin and Nails: The loss of E2 in menopause causes thinning of the skin and loss of Hair. As our understanding of the molecular and hormonal controls on the hair follicle has grown, there has been increased interest in the various modulators of hair growth, including the potential role of E2[25]

Osteoarthritis: Evidence is accumulating about the very positive effect of E2 on joints and preventing OA. In study from Denmark, they referred to E2 as a possible magic bullet in preventing OA. They found” The female predominance of polyarticular osteoarthritis (OA), and in particular the marked increase of OA in women after the menopause points to a likely involvement of female sex hormones in the maintenance of cartilage homeostasis. This is in complete alignment with clinical data using biochemical markers of joint degradation which demonstrated approximately 50% inhibition of cartilage destruction (with E2). These finding were recently validated in WHI, where women taking E2 had significantly less joint replacement[26].

Frailty:  There is solid evidence that E2 prevents loss of musculoskeletal tissue mass and quality, and the ability to respond to mechanical and metabolic stressors, like exercise.[27]

Voice: HRT seems to counteract the vocal changes caused by menopause. The type of HT did not affect the outcome in this study[28].

Weight Gain:  The hormonal changes across the perimenopause substantially contribute to increased abdominal obesity which leads to additional physical and psychological morbidity. There is strong evidence that E2 therapy may partly prevent this menopause-related change in body composition and the associated metabolic sequelae[29].

Diabetes:  HRT reduces the risk of diabetes and, through improving insulin action in women, with insulin resistance[30],[31],

Neuroprotection:  Ovarian hormones can protect against brain injury, neurodegeneration and cognitive decline[32]. Studies suggest that women are “protected” against stroke relative to men, at least until the years of menopause, when E2 levels fall. Studies further reveal that endogenous E2 production has a neuroprotective role in the brain against cerebral ischemia[33],[34]. E2 is intimately associated with neuronal survival, mitochondrial function, neuroinflammation and cognition through genomic as well as non-genomic pathways[35], E2 has been documented to be effective in treating the symptoms of Parkinson’s disease[36]. However, it is crucial that E2 replacement start at menopause or sooner. Any delay causes the neuroprotective benefits to be lost.

It is time that the medical profession reappraises our attitude to E2 as a result of these recent studies. Our patients also deserve to have this information so that they can make better informed decisions about using HRT containing E2, and the potential long-term benefit of taking E2.


[1] Quality of life of postmenopausal women on a regimen of transdermal estradiol therapy. Am J Obstet Gynecol 1993;168:824-30.

[2] Menopausal symptoms  and treatment-related effects of estrogen and progestin in the WHI. Obstet Gynecol 2005; 105:1063-1073

[3] NIH Conference Management of menopause related symptoms Ann Intern Med 2005;142:1003-1013

[4] The increased longevity in older users of postmenopausal estrogen therapy: the Leisure World Cohort Study, Menopause 2006 Jan-Feb;13(1):12-18 Gynecol 1993;168:824-30

[5] Hormone Replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study. JAMA 2002 Nov 6;288(17):2123-9-

[6] Lifelong estrogen exposure and memory in older postmenopausal women. J Alzheimers Dis 2013 Jan 1;34(3):601-8

[7] Hormone replacement therapy and the risk of colorectal cancer: a meta-analysis. Obstets Gynecol 1999;93:880-8

[8]Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis. Am J Med 1999:106:574-82

[9] Slattery et al HRT and improved survival among postmenopausal women diagnosed with colon cancer; Cancer causes control 1999;10:467-473.

[10] BMJ 2012;345:e6409.

[11] Cancer statistics 2010 Cancer j Clin 2010;60:277-300

[12] CEE and coronary heart disease The WHI. Arch Intern Med 2006;166:357-36

[13]Postmenopausal HRT and the risk of CVD by age and years since menopause JAMA 2007; 297:1465-1477

[14] HRT and CVD in the early menopause – the WHI data revisited. Climacteric 2007;10:195-196

[15] Ten reasons to be happy about hormone replacement therapy: a guide for patients. Studd,J.Menopause international 2010; 16; 44-46.

[16]. The comparative effect on bone density , endometrium and lipids of continuous HRT (CHART) study. Speroff et al JAMA 1996;276:1397-1403

[17] Ultra-low micronized beta estradiol and bone densityand bone metabolism in older women. Prestwood et al..JAMA 2003:290:1042-1048

[18] A guide to the treatment of depression in women by estrogens Climacteric 2011 Dec;14(6):637-42

[19] Depression during the menopausal transition. Menopause Int 2008 Sep;14(3):123-8

[20] Associations of hormones and menopausal status with depressed mood in women with no history of depression Arch Gen Psychiatry  2006;63:375-82

[21] Summary of the National Institute on Aging-sponsored conference on depressive symptoms.Menopause 2010;17:815-22

[22] The Seattle Midlife Women’s Health Study J Womens Health 2010 Feb;19(2) 209-18

[23] Sexuality in Midlife J Midlife Health 2012 Jul;3(2):61-5

[24] The use of estrogen therapy in women’s sexual function. J Sex Med 2009;6:603-1

[25] Managing hair loss in midlife women. Maturitas 2012 Nov 24 S0378-5122(12)00368-4

[26] The pathogenesis of osteoarthritis involves bone, cartilage and synovial inflammation:may estrogen be a magic bullet? Menopause Int 2012 Sep 28.

[27] Menopause, estrogens and Frailty. Nedergaard et al. Gynecol Endocrin 2013 May;29(5):418-23

[28] J voice. Sep;2012 26;(5) :671

[30] Updated IMS recommendations on postmenopausal hormone therapy. Climacteric 2011;14:302-320

[31] Effects of estrogen plus progestin on the incidence of diabetes in postmenopausal women. Results from the WHI study. Diabetologia 2004; 47:1175-1187

[32] Neuroprotection by ovarian hormones in animal models of neurological disease. Endocrine 2006 Apr; 29(2):217-31

[33] Estrogen signalling and neuroprotection in cerebral ischemia. J Neuroyndocrinol 2012 Jan;24(1):34-47

[34] Neuroprotection by estrogen. Ann N Y Acad Sci 2003 Dec:1007:89-100

[35] Effects of estrogen in the brain:is it a neuroprotective agent in Alzheimer’s disease? Curr Aging Sci. 2010 Jul; 3(2):113-26.

[36]From clinical evidence to molecular mechanisms underlying neuroprotection afforded by estrogens. Pharmacol Res 2005 Aug:52(2):119-

About Dr Colin Holloway

Gp interested in natural hormone treatment for men and women of all ages

Posted on August 14, 2013, in Uncategorized. Bookmark the permalink. 3 Comments.

  1. Hi there, after reading this remarkable paragraph i am too delighted to share my knowledge here with friends.

  2. certainly sounds pretty positive to me! I have the breast cancer gene and it wont stop me taking hrt, I love the benefits!

  3. marilynne dornan

    Excellent Colin.! Thank you!

    Date: Wed, 14 Aug 2013 22:16:53 +0000 To: marilynnedornan@hotmail.com

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