Think there is no research to support the use of BHRT? Think again!

I am sure you have read or heard someone say that there is no research to support the use of bioidentical hormones, often referred to as Bioidentical Hormone Replacement Therapy BHRT for short. One the other hand, proponents declare that there is plenty of supporting evidence.  Who is right? There certainly is a lot of conflicting information about bioidentical hormones and BHRT presented on the internet and thru the media.  There is no wonder health care providers as well as patients are confused. I will help sort it all out in this blog. 

 

Why the Confusion About BHRT Research Anyway?

Before I dispel the misinformation regarding the so-called lack of research on BHRT I want to address why there is even an argument in the first place. I propose that the main reason many have come to the conclusion that there is no research to support the use of BHRT is that when they peruse the data looking for studies on BHRT there isn’t much to find. That is because of this word “bioidentical” – it is not yet a medically accepted word.  It is more of a marketing or slang word.  All the same, personally I think it is an accurate way to describe hormones that are biologically identical to human endogenously produced hormones. (For more details read my previous blog WHAT ARE BIOIDENTICAL HORMONES AND ARE THEY SAFE FOR YOUR PATIENTS) When searching through medical data, what you dofind are studies on estradiol, progesterone, and testosterone.  The hormones often used in studies arebioidentical hormones. However, they do not use the word “bioidentical”, just the name of the real hormone as in estradiol, for example.

 

BHRT Research

 Actually, there are decades of published studies that first started showing up as early as 1976.  In addition, there are recent popular studies including the Keeps Study, the Danish Study, WHI, The Pepi Trial, E3N, and the Danish Nurses Cohort Study that shed more light on this debate.

 

Here is a summary of what these studies demonstrated in regard to bioidentical hormones:

1. Bioidentical hormones have distinctly different effects.
2. Patients report greater satisfaction with HRT using progesterone vs progestin.
3. Progesterone is associated with a diminished risk for breast cancer compared to increased risk with progestins.
4. Progestins have a variety of negative cardiovascular effects including reduction of HDL, etc.
5. Estriol, estradiol, estrone and CEE have different physiological effects.
6. Transdermal estradiol is not associated with the same risk as oral estradiol.
7. Hysterectomized women treated with estradiol showed significant decrease inbreast cancer and mortality​.
8. Estradiol can be continued for at least 10 years without an increase in adverseevents and does not result in increased risk of breast cancer or stroke​.

 

Research Comparing Bioidentical Hormones to Non-Bioidentical

Even more compelling is research that compares the effects of bioidentical hormones to non-bioidentical hormones.  Non-bioidentical hormones are hormones that have a different molecular structure than human hormones. These include Conjugated Equine Estrogen (CEE), Ethinyl Estradiol, or Medroxy Progestin Acetate for example. Here is the summary of what you need to know from the citations comparing non-bioidenticals to bioidenticals.​ I will share the references below for your review.

• Bioidentical hormones convey more favorable or equally effective results than non-bioidentical hormones.
• Bioidentical hormones are equally or more effective for these key symptoms sleep, mood, and vasomotor symptoms
• Bioidentical hormones have been shown to improve lipid profiles, be safer, and lack side effects demonstrated with non-bioidenticals.
• The risks associated with CEE and progestins in regard to breast cancer and cardiovascular events have not been reported with bioidentical hormones.

One of the most important things we have learned is that you cannot extrapolate the results from research done on one type of hormone and then apply it to a different type of hormone.  I recall the days when some uninformed medical professionals contended that all hormones are the same. That does not agree with what we know from basic chemistry – the molecular structure determines its properties.

Let it no longer be said there is no research on bioidentical hormones or they have not been shown to be safe.​  As you can see there isreputable data and furthermore bioidentical hormones have been demonstrated to be safer than their non-bioidentical counter parts.

I am convinced that patients prefer to work with open-minded, well-informed practitioners on this topic.  In fact, they are looking for you right now.  In addition to the fact that BHRT is evidenced based, not a fad compliance is very high.  Some clinicians estimate compliance is at least 90% or higher. As you know compliance on conventional HRT is very low.  Potential reasons for the poor compliance are assumed to be side effects or fear. In my 25+ years of experience in the field BHRT, women are seeking BHRT which makes them feel so much better.  Patients are well read now and want their providers to be resources they can trust to help manage their hormones.  With that in mind, in view of the growing body of research, as a provider you can confidently recommend and even begin to learn how to prescribe and implement BHRT into your practice.

Further Reading

Keeps Study

<http://www.menopause.org/annual-meetings/2012-meeting/keeps-report>

KEEPS study showed low dose estrogen and progesterone started within 5 years of menopause improved depression, anxiety, and cognitive function in healthy women without increased risk of CVD.

E3N

Int J Epidemiol. 2015 Jun;44(3):801-9. doi: 10.1093/ije/dyu184. Epub 2014 Sep 10.​

Data analyzed on 98,997 women concluding that progesterone regimens compared to synthetic progestin were associated with significantly lower breast cancer risks, and women that took HRT consistently were at lower risk of breast cancer than women who took HRT occasionally.

Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2008; 107(1):103-111.

Another European 8 yearlong cohort study on postmenopausal women on transdermal estradiol and progesterone found no increased risk for breast cancer.

De Lignières B, de Vathaire F, Fournier S, et al. Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women. Climacteric. 2002; 5:332-340.

Danish Nurses Cohort Study

Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomized trial.

BMJ 2012;345:e6409

Br J Cancer. 2005 Apr 11;92(7):1293-7​

Conducted on 19,898 women 45 years of age and older found the highest breast cancer risk to be in women who used continuous combined estrogen with synthetic progestin.

Stahlberg C, Pedersen A, Lynge E, et al. Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe. Int J Cancer. 2004; 109:721-727.

Research published in JAMA found CEE and estradiol equally effective in relief of hot flashes but CEE has long-term risk of blood clot, stroke, and MI.

Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes.

JAMA. 2004; 291(13):1610-1620.

PEPI Trial

Long term study on cardiovascular effects of both synthetic progestins and micronized progesterone with CEE. 

Writing group for the PEPI trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The postmenopausal estrogen/progestin interventions (PEPI) trial.

JAMA. 1995; 273:199-208.

NON-BIOIDENTICAL VS BIOIDENTICAL HRT – COMPARATIVE STUDIES

Bioidentical hormones convey more favorable or equally effective results than non-bioidentical hormones.

1 Stanczyk FZ. All progestins are not created equal. Steroids. 2003; 68:879-890.

2 Place V, Powers M, Schenkel L, et al. A double-blind comparative study of estraderm and premarin in the amelioration of postmenopausal symptoms. Am J Obstet Gynecol. 1985; 152(8):1092-1099.

3 Writing group for the PEPI trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA. 1995; 273:199-208.

 4 Good W, John V, Ramirez M, et al. Double-masked, multicenter study of an estradiol matrix transdermal delivery system (Alora™) versus placebo in postmenopausal women experiencing menopausal symptoms. Clin Ther. 1996; 18:1093-1105.

5 Stahlberg C, Pedersen A, Lynge E, et al. Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe. Int J Cancer. 2004; 109:721-727.

6 Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes.

JAMA. 2004; 291(13): 1610-1620.

7 Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2008; 107(1): 103-111.

8 De Lignières B, de Vathaire F, Fournier S, et al. Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women. Climacteric. 2002; 5:332-340.

Bioidentical HRT Effective for Symptoms (Sleep, Mood and Vasomotor), Safer, Lack of Side Effects, No Risk of Breast Cancer, Improved Lipid Profiles.

1 Stahlberg C, Pedersen A, Lynge E, et al. Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe. Int J Cancer. 2004; 109:721-727.

2 Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2008; 107(1): 103-111.

3 De Lignières B, de Vathaire F, Fournier S, et al. Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women. Climacteric. 2002; 5: 332-340.

4 Grady D, Vittinghoff E, Lin F, et al. Effect of ultra-low-dose transdermal estradiol on breast density in postmenopausal women.Menopause J North Am Men Soc. 2007; 14(3):1-6.

5 Simon JA, Bouchard C, Waldbaum A, et al. Low dose of transdermal estradiol (E2) gel for treatment of symptomatic postmenopausal women. Obstet Gynecol. 2007; 109(2):1-10.

6 Montplaisir J, Lorrain J, Denesle R, et al. Sleep in menopause: differential effects of two forms of hormone replacement therapy. Menopause. 2001;8(1): 10-16.

7 Gambacciani M, Ciaponi M, Cappagli B, et al. Effects of low-dose, continuous combined hormone replacement therapy on sleep in symptomatic postmenopausal women. Maturitas. 2005; 50:91-97.

8 Zegura B, Guzic-Salobir B, Sebestjen M, et al. The effect of various menopausal hormone therapies on markers of inflammation, coagulation, fibrinolysis, lipids, and lipoproteins in healthy postmenopausal women. Menopause. 2006; 13(4):643-650.

The risks associated with CEE and progestins in regard to breast cancer, cardiovascular events have not been reported with bioidentical hormones.

1 Stanczyk FZ. All progestins are not created equal. Steroids. 2003; 68:879-890.

2 Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2008; 107(1):103-111.

3 De Lignières B, de Vathaire F, Fournier S, et al. Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women. Climacteric. 2002; 5:332-340.

4 Santen RJ. Risk of breast cancer with progestins: critical assessment of current data.

Steroids. 2003; 68:953-964.

5 Schairer C, Lubin J, Troisi R, et al. Menopausal estrogen and estrogen-progestin replacement therapy and

breast cancer risk. JAMA. 2000; 283:485-491.

6 Schindler A. European Progestin Club. Differential effects of progestins. Maturitas. 2003; 46: S3-S5.

7 Grady D, Vittinghoff E, Lin F, et al. Effect of ultra-low-dose transdermal estradiol on breast density in postmenopausal women.Menopause J North Am Men Soc. 2007; 14(3):1-6.

8 Simon JA, Bouchard C, Waldbaum A, et al. Low dose of transdermal estradiol (E2) gel for treatment of symptomatic postmenopausal women. Obstet Gynecol. 2007; 109(2):1-10.

9 Montplaisir J, Lorrain J, Denesle R, et al. Sleep in menopause: differential effects of two forms of hormone replacement therapy. Menopause. 2001; 8(1): 10-16.

10 Gambacciani M, Ciaponi M, Cappagli B, et al. Effects of low-dose, continuous combined hormone replacement therapy on sleep in symptomatic postmenopausal women. Maturitas. 2005; 50:91-97.

11 Zegura B, Guzic-Salobir B, Sebestjen M, et al. The effect of various menopausal hormone therapies on markers of inflammation, coagulation, fibrinolysis, lipids, and lipoproteins in healthy postmenopausal women. Menopause. 2006; 13(4):643-650.

12 Rossow J, Anderson G, Prentice R, et al. Writing Group for the Women’s Health Initiative. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA. 2002; 288(3):321-333.

13 Wassertheil-Smoller S, Hendrix S, Limacher M, et al. Effects of estrogen plus progestin on stroke in postmenopausal women. The women’s health initiative: a randomized trial. JAMA. 2003; 289(20):2673-2684

14 Porch J, Lee I, Cook N, et al. Estrogen-progestin replacement therapy and breast cancer risk: the women’s health study (United States). Cancer Causes Control. 2002; 13:847-854.

15 Statement on the estrogen plus progestin trial of the Women’s Health Initiative. ACOG News release. 2002.