What is the difference between Natural hormones and the hormones most doctors prescribe?

My patients often say that their own doctors tell them  there is no difference between Bio-identical HRT and the hormones they use. Ha! If only. The difference is the same as between Apples and Oranges. They are both fruit, but totally different. Another example is that of sugar. Sugar is a natural sweetener, compared to Aspartame or saccharin, which are synthetic sweeteners. They are very different. The difference between natural and synthetic hormones is sometimes as different  as that  of apples and oranges, or sugar and saccharine.

 I will do my best to present a clear picture of the reasons why Natural, also called Bio-identical, or Body-identical, HRT is better than the standard HRT used by most doctors and specialists.  See the chapters marked Evidence for BHRT and safety of BHRT for more information. Feel free to comment at the end of the chapter.

Some terminology will need to be clarified first.

Micronized: Progesterone can be micronized by making very tiny crystals of the progesterone. Micronized progesterone is manufactured in a laboratory from plants. It is available for use as HRT, infertility treatment, treat progesterone deficiency (PMS), including dysfunctional uterine bleeding in premenopausal women. Compounding pharmacies can supply micronized progesterone in sublingual tablets, oil caps, or transdermal creams.

Progestogen consists of Medroxyprogesterone acetate ( Provera) and Norethisterone (Primolut), the main hormones used in synthetic HRT. Note: these are nothing like the progesterone made by the body.  Some newer ones are drospirone, which are better, but still not as good as the real thing.

Now here is the official recommendations from various professional bodies:

Guidelines from the North American Menopause Society, the Endocrine Society, the International Menopause Society, and specific guidelines from the European Menopause and Andropause Society for the management of menopausal women with a personal or family history of VTE  (VenousThromboEmbolism) all contain positive statements regarding both transdermal estradiol and micronized progesterone.

 Based on these data, which are now included in the guidelines, the use of transdermal estradiol and micronized progesterone could reduce or possibly even negate the excess risk of VTE, stroke, cholecystitis, and possibly even breast cancer associated with oral HRT use.(Climacteric April 2012)

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The European Menopause Association, in their recommendations, stated:

 It is important to include in the evaluation of the balance between benefits and risks of HRT the increase in quality of life and climacteric symptoms. It can be speculated, in view of this reappraisal of HRT effects in the WHI trials, that prescribing HRT to symptomatic women using more natural hormones and route of administration may even improve the beneficial effects.

 

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The Position statement from the North American Menopause society states:

Data from a large observational study suggest that EPT with micronized progesterone carries a low risk of breast cancer with short-term use but carries an increased risk of breast cancer with all EPT formulations with long-term use.

Tailoring the dose to a woman’s individual needs represents an appropriate strategy in HT management.
Lower HT doses generally have fewer adverse effects, such as breast tenderness and uterine bleeding, and may have a more favorable benefit-risk ratio than standard doses. In a nested case-control study from the UK General Practice Research database, the risk of stroke was not increased with low-dose transdermal estrogen (e0.05 mg) but did increase with oral therapies and with higher transdermal doses.

Menopause: The Journal of The North American Menopause Society
Vol. 19, No. 3, pp. 257/271
DOI: 10.1097/gme.0b013e31824b970a

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From Climacteric Apr 2012 again:

Micronized progesterone does not increase cell proliferation in breast tissue in postmenopausal women compared with synthetic medroxyprogesterone acetate (MPA). Experimental evidence suggests that the opposing effects of MPA and micronized progesterone on breast tissue are related to the non-specific effects of MPA, including glucocorticoid activity and differences in the regulation of gene expression. Therefore, for women with an intact uterus, micronized progesterone may be the optimal choice as part of combined HRT

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This from Gynecology Fertility 2006:

Transdermally administered estradiol has been shown to be an efficacious treatment for hot flushes possibly without the increase in blood clotting that is associated with administration of oral CEE. Further, natural progesterone may have a more beneficial spectrum of physiological effects than synthetic progestins.”

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In the Annals of endocrinology 2007, Cauffriez, from the school of Medicine, Brussels said:

The combination of transdermal estradiol+micronized progesterone appears to be effective and relatively safe if elementary precautions are taken, and seems to be presently the best choice for HRT in most postmenopausal women.

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Holtorf, in Postgraduate Medicine (one of the top ranked peer reviewed medical journals) 2009 said:

Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal-derived counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT. Further randomized controlled trials are needed to delineate these differences more clearly.

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From Maturitas, the journal of the European Menopause Association, 2007, l;Hermite University of Brussels:

Recent evidence indeed shows that natural progesterone displays a favorable action on the vessels and on the brain, while this might not be true for some synthetic progestins. Compelling indications also exist that differences might also be present for the risk of developing breast cancer, with recent trials indicating that the association of natural progesterone with estrogens confers less or even no risk of breast cancer as opposed to the use of other synthetic progestins. In conclusion, while all types of hormone replacement therapies are safe and effective and confer significant benefits in the long-term when initiated in young postmenopausal women, in specific clinical settings the choice of the transdermal route of administration of estrogens and the use of natural progesterone might offer significant benefits and added safety.

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This very important article from the Editors of Climacteric, titled “Bio-identical HRT – why all the fuss?”

Fundamental differences exist between conjugated equine estrogens and 17fi-estradiol and between medroxyprogesterone acetate (MPA) and natural progesterone.

 This Editorial explores the possibility that different outcomes might be achieved, not only by varying the dose and age of initiation, but by the use of bio­identical hormones.

What are bioidentical hormones?

Bioidentical hormones are precise duplicates of estradiol, progesterone and testosterone as synthe­sized by the human ovary. They are manufactured from plant sources in the laboratory and are available from pharma companies as micronized oral tablets, transdermal patches, implants and gels. Other possible delivery routes include nasal and wafer forms.

So are there any differences between bioidentical and non-bioidentical hormones?

The most significant difference, in terms of biological effect, is in the progesterone compo­nent. The synthetic analogs of progesterone, i.e. progestins/progestogens, were developed to make the hormone available orally before the process of micronization had been developed. Unfortunately, in addition to binding to the progesterone recep­tor, many of these compounds also bind to the glucocorticoid, mineralocorticoid and androgen receptors. This binding can lead to unwanted side­effects such as unfavorable glucose metabolism, fluid retention, acne and weight gain3. The natural progesterone molecule binds primarily to the progesterone receptors to produce the desired effect on the endometrium.

Effect on the cardiovascular system

Natural progesterone has several properties that facilitate a neutral or positive effect on the cardiovascular system. There appears to be a neutral effect on lipid and glucose metabolism and on vascular tone. Thus, the beneficial effects of estrogen are not attenuated as they are with some synthetic progestins such as MPA, which can blunt the increases in high density lipoprotein cholesterol4. Progesterone also has beneficial effects in preventing the growth and movement of cells involved in the formation of arteriosclero­tic plaques and relaxing arterial smooth muscle via enhancement of nitric oxide from the en­dothelium. Conjugated equine estrogens lead to greater increases in triglycerides than 17fi-estra­diol but it is unclear how significant this is as far as cardiovascular disease risk is concerned.

The published data thus far suggest that differential effects can be achieved by the use of body-identical hormones in com­parison to synthetic non-body-identical HRT

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This comes from an impeccable source:

CLIMACTERIC 2011;14:302–320

Updated IMS recommendations on postmenopausal hormone therapy and preventive strategies for midlife health

D. W. Sturdee and A. Pines on behalf of the International Menopause Society Writing Group

Writing Group: D. F. Archer, R. J. Baber, D. Barlow, M. H. Birkha¨user, M. Brincat, L. Cardozo, T. J. de Villiers,

  1. Gambacciani, A. A. Gompel, V. W. Henderson, C. Kluft, R. A. Lobo, A. H. MacLennan, J. Marsden, R. E. Nappi,
  2. Panay, J. H. Pickar, D. Robinson, J. Simon, R. L. Sitruk-Ware and J. C. Stevenson (My comment – these are all the top brass in Hormone knowledge and experience)

There are insufficient data to evaluate the possible differences in the incidence of breast cancer using different types, doses and routes of estrogen, natural progesterone and progestogens and androgen administration. Nevertheless, large European observational studies suggest that a difference in risk between estrogen-only and combined estrogen– progestogen therapy is seen with some categories of progesto­gens but not with natural progesterone derivatives.

. Micronized progesterone or dydrogesterone used in association with oral or percutaneous estradiol may be associated with a better risk profile for breast cancer than synthetic progestogens for at least 5 years, but there are not as yet adequately powered clinical studies.

In general, progestogen should be added to systemic estrogen for all women with a uterus to prevent endometrial hyperplasia and cancer. However, natural progesterone and some progestogens have specific beneficial effects that could justify their use besides the expected actions on the endometrium

The  American Association of Clinical Endocrinologists Medical Guidelines for clinical Practice for the Diagnosis and Treatment of Menopause, Nov/Dec 2011, in Endocrine Practice Vol 17. stated:

The choice of progestational agent may be the most important factor in observations of breast cancer risk.  Risk studies suggest that the use of micronized progesterone in comparison with medroxyprogesterone and the avoidance of combined continuous therapy may be associated with a lower risk of breast cancer in MHT users.

Each postmenopausal woman should be provided with an individualized evaluation regarding the benefits and risks of MHT, in consultation with her treating physician. The “one-size-fits-all” approach to education, counseling and treatment, is inappropriate.

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Int J Pharm Compd. 2013 Jan-Feb;17(1):74-85.

The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women.

Abstract

Menopause impacts 25 million women world wide each year, and the World Health Organization estimates 1.2 billion women will be postmenopausal by 2030.

Menopause has been associated with symptoms of hot flashes, night sweats, dysphoric mood, sleep disturbance, and conditions of cardiovascular disease, depression, osteoporosis, osteoarthritis, depression, dementia, and frailty.

Conventional hormone replacement therapy results in increased thrombotic events, and an increased risk of breast cancer and dementia as evidenced in large prospective clinical trials including Heart and Estrogen/Progestin Replacement Study I and the Women’s Health Initiative. A possible mechanism for these adverse events is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on the hemostatic balance and inflammatory and immune factors. Physiologic sex steroid therapy with transdermal delivery for peri/postmenopausal women may offer a different risk/benefit profile, yet long-term studies of this treatment model are lacking. The objective of this study was to examine the long-term effects of compounded bioidentical transdermal sex steroid therapy including estriol, estradiol, progesterone, DHEA, and testosterone on cardiovascular biomarkers, hemostatic, inflammatory, immune signaling factors; quality-of-life measures; and health outcomes in peri/postmenopausal women within the context of a hormone restoration model of care. A prospective, cohort, closed-label study received approval from the Human Subjects Committee. Recruitment from outpatient clinics at an academic medical center and the community at large resulted in three hundred women giving signed consent. Seventy-five women who met strict inclusion/exclusion criteria were enrolled. Baseline hormone evaluation was performed along with baseline experimental measures. Following this, women received compounded transdermal bioidentical hormone therapy of BiEst (80%Estriol/20%Estradiol), and/or Progesterone for eight weeks to meet established physiologic reference ranges for the luteal phase in premenopausal women. The luteal phase hormone ratios were selected based on animal and epidemiologic studies demonstrating favorable outcomes related to traumatic, ischemic, or neuronal injury. Follow-up testing was performed at eight weeks and adjustment to hormone regimens were made including addition of androgens of DHEA and Testosterone if indicated. Experimental subjects were monitored for 36 months. Baseline, 2-month, and annual values were obtained for: blood pressure, body mass index, fasting glucose, Homeostasis Metabolic Assessment of Insulin Resistance (HOMA-IR), fasting triglycerides, total Factor VII, Factor VIII, fibrinogen, Antithrombin III, Plasminogen Activator Inhibitor1(PAL-1), C-reactive protein (CRP), Interleukin-6 (IL-6), Matrix Metalloproteinase-9 (MMP-9), Tumor Necrosis Factor-alpha (TNF), Insulin-like Growth Factor (IGF-1), and sex steroid levels. Psychosocial measures included: Greene Climacteric Scale, Visual Analog Pain Scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Holmes Rahe Stress Scale, Job Strain, and Home Strain. Health outcome measures included the number of prescribed medications used, number of co-morbidities, and endometrial thickness in postmenopausal women with intact uteri.

Subjects receiving compounded transdermal bioidentical hormone therapy showed significant favorable changes in: Greene Climacteric Scale scores, Hamilton Anxiety Scale, Hamilton Depression Scale, Visual Analog Pain Scale, fasting glucose, fasting triglycerides, MMP-9, C-reactive Protein, fibrinogen, Factor VII, Factor VIII, Insulin-Like Growth Factor 1, and health outcomes of co-morbidities and a number of prescribed medications. Antithrombin III levels were significantly decreased at 36 months.

All other measures did not exhibit significant effects. Administration of compounded transdermal bioidentical hormone therapy in doses targeted to physiologic reference ranges administered in a daily dose significantly relieved menopausal symptoms in peri/postmenopausal women. Cardiovascular biomarkers, inflammatory factors, immune signaling factors, and health outcomes were favorably impacted, despite very high life stress, and home and work strain in study subjects. The therapy did not adversely alter the net prothrombotic potential, and there were no associated adverse events. This model of care warrants consideration as an effective and safe clinical therapy for peri/postmenopausal women especially in populations with high perceived stress and a history of stressful life events prior to, or during the menopausal transition

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My Comment: I hope these articles, all taken from mainstream medical journals, from the top experts in the field, help you to understand the importance of using Bio-identical HRT as compared to the synthetic form. I have much more information on the same line, but this should be sufficient for even the most doubting Thomas’s. Feel free to comment below.

  1. Ring your nearest compounding chemist and ask them to refer you to someone who uses BHRT

  2. Hi there, thank you for the comprehensive outline of biochemical hormone replacement. A great read.
    I am at my end of knowing what to do and very long suffering. I live in Southern Sydney (the shire) and can you recommend someone I can see here along the same lines as you? I look forward to hearing from you.

  3. Hi Dr Holloway! Thanks for sharing such informative articles!

    http://bioidentical-testosterone.com/

  4. Livial’s chemical name is Tibolone. There is nothing like it in the human body i.e. it is totally synthetic. As such, it has many side effects, mainly an increased risk of Breast cancer and strokes. There is a summary of it on my web-site (search “livial” in the search engine.)

  5. How does livial compare to bioidentical hormones? It seems to be different from the conventional ones, but it is also different from the bio identical

  6. I’m impressed, I have to admit. Rarely do I encounter a blog that’s equally educative
    and amusing, and without a doubt, you have hit the nail on
    the head. The problem is an issue that too few folks
    are speaking intelligently about. I am very happy I stumbled across this during my search for something relating to
    this.

  7. Not at all. If I do blood test for progesterone when you are taking dydrogesterone, it will not show up. Although this may be an improvement on the previous progestogens, it still not as good as the real thing – progesterone. Women’s bodies have taken millions of years to get it right- progesterone. I doubt we can improve on it in our laboratories.

  8. I would like to know, how similar is dydrogesterone to bio identical progesterone.

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