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BHRT and Cardiovascular Health: Understanding the Connection

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Written by

Science&Humans

Medically approved by

Medically approved by

Maria Jacob

Last updated

Tuesday, February 27, 2024

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Estrogen and progesterone are keys to executing some of the most important functions in the body – especially in terms of cardiovascular health. Hence, menopause, leading to drastic levels of reduction in the amounts of these hormones makes women vulnerable to heart diseases.

Bioidentical hormone replacement therapy for women uses formulations structurally similar and with similar receptors as produced endogenously by the human body but from plant sources in the laboratory.

Hence there are bound to be concerns regarding BHRT therapy for heart health - the potential of bioidentical hormones in reviving the crucial cardiovascular functions served by estrogen and progesterone. Clinical trials thus far have shown positive results but it all depends on the dosing, duration and most importantly, the timing of initiation of therapy. These hormones are only to be taken if prescribed by a licensed practitioner.

The Impact Of Hormones On Cardiovascular Health

The dynamics between hormones and cardiovascular diseases are complex. No one situation or condition can explain another one. Healthy, premenopausal females with normal lipid profiles and without any history of diseases are less prone to cardiovascular diseases (CVD) than those in the ageing population and even in age-matched men.(1) Women, especially after menopause, are more prone to developing CVD which also contributes to the highest mortality in numbers, globally.(1

Women in their reproductive ages have the right amounts of hormones (particularly estrogen) to perform key bodily functions (described in detail in the next segment). Combining the fact that the incidence of any form of CVD – be it hypertension, atherosclerosis, myocardial dysfunction, ventricular hypertrophy, heart failure, or myocardial ischemia is particularly low among these women.(2) Women with polycystic ovarian syndrome (PCOS) are also not under threat for CVD although hypertension and diabetes are risk factors.(2

Women who are on combined hormonal contraception are also not predisposed to CVD risks at their age. However, women in this age group with pre-existing risk factors like a family history of heart disease or existing cases of CVD should exercise any form of external hormone therapy, (like contraception or birth control) with great caution and only under medical guidance.(2)

Hormonal Imbalances And Cardiovascular Risk Factors

A key reason for menopausal women to be predisposed to CVD is the exhaustion of estradiol (E2), which has the strongest biological activity and is the most effective form of estrogen in the body. The main source of estrogen production in the body is the cholesterol in the ovaries, corpus luteum, and placenta in premenopausal women. A small amount of estrogen is also produced by nonovarian organs, such as the liver, heart, skin, and brain.(1) In menopausal and postmenopausal  women, due to the depletion of eggs in the ovaries, estrogen is produced by extragonadal tissues and acts locally by paracrine or endocrine means to maintain tissue-specific functions. However, the amount of estradiol is significantly reduced. As a result of declining estradiol levels, there is oxidative stress (OS) in which is caused due to an imbalance between the body’s oxidation system and the antioxidant defense system. (1) (3)

OS leads to cellular dysfunction, increase in the levels of fatty acids, vasculitis, deposition of low-density lipoprotein (LDL) in the walls of the arteries, which increase chances of development of ischemia/reperfusion (IR), hypertensive heart disease, cardiomyopathy, atherosclerosis, and heart failure. 

As per current scientific evidence, menopausal hormone therapy implemented at the earliest will be beneficial (with cardioprotective effects) for women who are not over 60 years old and are not predisposed to cardiovascular risk factors, stroke, or blood-clots (thromboembolism).(4) (5) It is crucial for women to understand their bodies transforming and entering menopause and the subsequent after-effects. If there are severe menopausal or post-menopausal symptoms, they should contact their gynecologists at the earliest.

What Role Does BHRT Play In Managing Cardiovascular Health?

Bioidentical hormone replacement therapy for women (BHRT) is under extensive research for all possible indications in the present time. One observational study has shown that bioidentical hormones in transdermal patches may be associated with a lower risk of heart attack, and FDA-approved products - not compounded hormones - may be associated with a slightly lower risk of stroke compared to synthetic hormones delivered orally via pills.(6) Some evidence also suggests that BHRT might be useful in improving cardiovascular outcomes for menopausal women provided they are regulated and are not synthetic.(7) The term body-identical has been coined to refer to regulated BHRT (rBHRT) only.

Different rBHRT include 17-betaestradiol (E2), 17-betaestradiol and micronized progesterone, Transdermal estradiol hemi-hydrategel, and micronized progesterone. 

The ways by which bioidentical hormone therapy and cardiovascular health are linked is similar to that of the natural hormones, because most regulated BHRTs are estrogen and progesterone molecules synthesized in a laboratory from plant sources, with identical molecular structures and similar estrogen receptors as human, endogenous hormones. It is their potency which remains to be assessed in clinical trials.

BHRT And Heart Health: Current Research On BHRT As A Preventive Measure For Cardiovascular Diseases

The impact of any form of hormonal therapy is dependent on the individual patient profile, their medical history and the practitioner’s/expert’s opinion. However, there have been isolated studies researching on the impact of BHRT on heart health and its different aspects.

In a 5-year trial with 596 postmenopausal women, only one patient taking rBHRT (17-betaestradiol [E2]) experienced a myocardial infarction, and three women reported deep vein thrombosis or pulmonary embolism. In another randomized control trial with 727 menopausal women receiving transdermal E2 only two women experienced thromboembolism. (7) In another randomized control trial with 313 postmenopausal women receiving a combination of progestin and estrogen BHRT, only one case of coronary artery disease was reported.(7) Similarly, no harmful effects were found when the use of BHRT was assessed for its effect on lipid profiles, chances of cardiomyopathy and carotid artery mean thickness.

Thus it is safe to say that there are isolated instances which have shown that BHRT and cardiovascular risk are not directly correlated, and that BHRT can be safely given to postmenopausal women provided they are treated early in menopause and are at a lower risk of CVDs or thromboembolism.(4) Though larger scale studies are still warranted to have a universal opinion, the rate of success and efficacy of any BHRT depends on the timing of the treatment, patient histories and the specialist’s evaluation.

The Influence Of Different Hormones On Cardiovascular System

The timing of dosage and the formulation and mode of delivery are crucial to ensuring an effective delivery. Oral pills are easy to prescribe and adhere to, but can lead to liver toxicity. Patches carry the risk of possible skin cancer for some patients and intramuscular injections can be painful for some people due to fear of needles, and can also cause unnecessary side-effects if injected in excess. Topical gels limit the absorption of the product and if used in the genital areas, can be dangerous for people and their partners during sexual intercourse or if they are in contact with children. Equally important is to understand the menopause-related hormonal symptoms early and then speak to a specialist for expert opinion.

As far as safety of BHRT is concerned, some of the regulated formulations are safe and efficient since they have been cleared by the FDA. However, pharmacies offer compounded formulations as well, which are not regulated and are dependent on the prescriber’s knowledge and individual patient medical histories. There should be adequate due diligence on the suppliers of the ingredients before consuming any compounded medication.

Safety Concerns Of BHRT Concerning Heart Health

The timing of dosage and the formulation and mode of delivery are crucial to ensuring an effective delivery. Oral pills are easy to prescribe and adhere to, but can lead to liver toxicity. Patches carry the risk of possible skin cancer for some patients and intramuscular injections can be painful for some people due to fear of needles, and can also cause unnecessary side-effects if injected in excess. Topical gels limit the absorption of the product and if used in the genital areas, can be dangerous for people and their partners during sexual intercourse or if they are in contact with children. Equally important is to understand the menopause-related hormonal symptoms early and then speak to a specialist for expert opinion.

As far as safety of BHRT is concerned, some of the regulated formulations are safe and efficient since they have been cleared by the FDA. However, pharmacies offer compounded formulations as well, which are not regulated and are dependent on the prescriber’s knowledge and individual patient medical histories. There should be adequate due diligence on the suppliers of the ingredients before consuming any compounded medication.

Conclusion

Bioidentical hormone replacement therapy is a considerably new chapter which is under intensive research for its claims on different aspects of health – especially on cardiovascular health. However, if the patient is diagnosed with any menopausal syndrome in the early phase of menopause, then safe and effective BHRT can be prescribed based on currently available knowledge, but only by a licensed practitioner.

However, there is no one formula that fits all. Every individual will have a different system and a different diagnosis. Not everyone undergoing menopause will need BHRT. But is one is prescribed any form of BHRT, there should be adequate understanding on the topic, and if a compounded formula is prescribed, then a prior due diligence on the pharmacy, the ingredients and the suppliers of the ingredients needs to be conducted on the patient’s part as well as on the prescribing physician’s part. 

FAQs

Q.  Does BHRT cause a heart attack?

A. If a licensed practitioner has prescribed a specific formulation of BHRT after a thorough diagnosis of the situation, you can be assured that it will not cause a heart attack for you. But you cannot say this for someone else who told you they have the same conditions. They need to consult their doctors before they start any medication.

Q. Does BHRT eliminate heart attacks?

A. BHRT will only eliminate any additional chance of a heart attack you may have because of a hormonal imbalance in your body post menopause. However, to think that taking any BHRT prevents all heart attacks is wrong. Please consult a licensed practitioner and discuss your medical history before referring to any form of treatment.

 References

  • Xiang D, Liu Y, Zhou S, Zhou E, Wang Y. Protective Effects of Estrogen on Cardiovascular Disease Mediated by Oxidative Stress. Oxid Med Cell Longev. 2021 Jun 29;2021:e5523516.

  • The ESHRE Capri Workshop Group. Hormones and cardiovascular health in women. Hum Reprod Update. 2006 Sep 1;12(5):483–97.

  • Cagnacci A, Gazzo I, Stigliani S, Paoletti AM, Anserini P, Londero AP, et al. Oxidative Stress: The Role of Estrogen and Progesterone. J Clin Med. 2023 Nov 25;12(23):7304.

  • Hormone Therapy and Heart Disease [Internet]. [cited 2023 Dec 19]. Available from: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2013/06/hormone-therapy-and-heart-disease

  • Hodis HN, Mack WJ. Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease: It’s About Time and Timing. Cancer J Sudbury Mass. 2022;28(3):208–23.

  • Study: Different Hormone Therapy Formulations May Pose Different Risks for Heart Attack and Stroke [Internet]. [cited 2024 Jan 12]. Study: Different Hormone Therapy Formulations May Pose Different Risks for Heart Attack and Stroke. Available from: https://www.cedars-sinai.org/newsroom/study-different-hormone-therapy-formulations-may-pose-different-risks-for-heart-attack-and-stroke/

  • Donnelly L, Balneaves LG. Fact or Fiction? The Role of Regulated Body-Identical Hormone Therapy for Menopausal Women. Nurs Womens Health. 2022 Apr 1;26(2):143–51.

  • Thomas P, Pang Y. Protective actions of progesterone in the cardiovascular system: potential role of membrane progesterone receptors (mPRs) in mediating rapid effects. Steroids. 2013 Jun;78(6):583–8.

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