Technology

A fine balance

In spite of offering many advantages over synthetic hormones, bio-identical hormone replacement therapy (BIHRT) finds few takers. Suja Nair finds out why

As key drivers of our emotions, hormones regulate all body functions, orchestrating cell responses through each organ and muscle. The discovery of hormones and endocrine interactions has led to subsequent understanding of hormone related pathophysiology that helped in developing new strategies in medical treatment such as fertility control and diabetes management. Cancer, cardiovascular afflictions and mental disorders too can be better managed today thanks to our better understanding of the role of hormones.

However, this fine balancing act performed by hormones can also go off track. Dr Anoop Chaturvedi, President, Anti-ageing Medicine and Research India (AMAR), and Research Director, Anti-Ageing Medicine AMARI Clinics, informs, "Earlier it was thought that as we age our hormones decline, but now there is enough scientific data to prove that we age because our hormones decline. With the decline of hormones, many diseases and disorders due to hormone deficiency start showing up in both men and women. Few years ago, hormone replacement therapy (HRT) was considered equivalent to oestrogen replacement therapy alone, which was using conjugated equine oestrogen (horse oestrogen) for relieving menopausal symptoms in women. But now, after the widespread knowledge of the neuroendocrinology of ageing and related health issues, bio-identical hormone replacement therapy (BIHRT) is used for prevention as well as treatment of conditions like osteoporosis, insulin resistance (metabolic syndrome), hypothyroidism, obesity, hypercholesterolemia, multiple sclerosis etc."

Gift from nature

"Although bio identical hormones are natural and safe, they are still hormones, and need judicious monitoring which makes the physician's involvement in the treatment necessary. Unsupervised and inaccurate dosing can cause usual side effects as with any medicine. In therapeutic monitored doses, the side effects are either very minimal or absent as compared to synthetic hormones" - Dr Anoop Chaturvedi President Anti-ageing Medicine and Research India (AMAR) Research Director Anti-Ageing Medicine AMARI Clinics

Bio identical hormones are natural as they originate from plant material. The starting material is a molecule disogenin, most often retrieved from wild Mexican yams and soybeans, from which hormones like oestrogen, progesterone, dehydroepiandrosterone (DHEA) and testosterone are derived. They are then slightly modified in a laboratory to attain a structure identical to the hormones produced by our own body. Bio-identical hormone therapy is equivalent to human identical hormone replacement therapy and is also known as iso-molecular hormone replacement therapy.

Chaturvedi asserts, "Use of this type of therapy is preferred by both men and women in dealing with hormonal changes due to ageing, menopause and andropause. On the other hand, most synthetic hormones or non iso-molecular hormones are those which have hormone like properties, but do not have exactly the same structure as compared to the hormones produced by our endocrine glands." Chaturvedi explains that most synthetic hormones use natural iso-molecular hormones as the base and then make synthetic molecular changes by adding extra chemical structures to increase the strength and potency, but it also increases the incidence of unwanted side effects as compared to the iso-molecular hormones.

Common examples of such therapies in use include medroxy-progesterone, a progestin, which has two to three times stronger affinity to receptors than natural progesterone. Similarly, premarin is conjugated equine oestrogen which is extracted from the urine of pregnant mares. It is 75 to 1,000 times stronger than natural estradiol. Unfortunately, it is devoid of the estriol (E3) component of human oestrogen which protects from breast cancer. In addition, it contains equillin, (equine oestrogen) which is known to be pro-carcinogenic to humans.

Dr Mahendra Parikh, in-charge of the Ageing and Anti-ageing Programme of the Federation of Obstetric and Gynecological Societies of India (FOGSI), and Editor Emeritus of the Journal of Obstetrics and Gynecology of India, explains, "BIHRT is applicable to any hormone produced by the body. One of its most common applications is to maintain normal hormone levels in perimenopausal women and during most of their postmenopausal life. The dosages of various hormones required vary from person to person and the pharmacy dispenses the requisite bioidentical hormones as per the individualised prescription given by the treating physician."

What's the difference?

Bio-identical hormones have exactly the same structure as those which occur naturally within our bodies. Hence, these molecules have exactly the same effect on the body as the original hormone when given to an individual as a restorative measure. While synthetically manufactured hormones are similar in chemical structure, but not the same as those produced by the body, synthetic hormones are different enough to have some dramatic side effects. As naturally occurring molecules cannot be patented, pharma companies developed synthetic hormones to enable them to patent and market these as therapies. However, all this changed with compounding, as it helped in getting an alternative to synthetic hormone replacement therapy. Compounding allows a pharmacist to use plant derived bio-identical hormones to customise a patient's hormone replacement therapy regimen to suit their needs better than the preset doses commercially available. Customising hormone replacement therapy ensures that specific hormone imbalances are addressed, and consequently, hormone levels are more accurately balanced.

Weighing against odds

Though BIHRT is widely practiced in US and European countries, it is not approved by the US Food and Drug Administration (US FDA). In India too it is not approved by the FDA, though it is widely used. In early January, the US FDA sent warning letters to seven pharmacies that made unsupported claims that their prepared hormone therapies were bio-identical to those FDA-approved treatment options for menopause symptoms, in some cases referring to them as ‘superior products’. BIHRT often involves use of estriol, a drug that has never been approved by the agency. The USFDA stated that pharmacies wishing to use estriol as an ingredient in any product must now submit either an investigational or a new drug application (NDA), and undergo a formal review.

The lack of standardisation of rules and procedures between pharmacies is believed to be the main reason for not getting the FDA nod. Parikh says that apparently no side effects are expected, barring those resulting from excessive dosages prescribed and/or administered. It is said that in the US a million prescriptions are dispensed every year by pharmacies, although they are not covered by standard health insurance policies. In India, physicians are being trained by a couple of agencies, but they need to be authorised to use them.

As with any prescription medication, the pros and cons of using BIHRT must be carefully weighed. Studies show that BIHRT in physiological doses produces significantly fewer negative side effects than synthetic hormones. Many patients have reported no negative side effects while using BIHRT.

Better delivery systems

To address hormone imbalances, patients need to first do a blood hormone test. Based on the analysis results, their physician will determine the current hormonal levels and then prescribe accurately to correct the imbalance. In many cases, more than one hormone will be prescribed in combination to achieve the optimal hormonal balance. BIHRT is most commonly and conveniently administered by sublingual delivery via troches (lozenges). However, oral delivery (via capsules) and transdermal delivery (via creams or gels) can also be used to administer it.

Delivery and administration systems of BIHRT have improved in the past few years, offering patients relief. In contrast to injectable and oral administration of synthetic derivatives which lead to steep high and low levels of hormones in the body, most BIHRT products (for example, oestrogen and progesterone creams used to control post menopausal symptoms) are available as creams, which need to be rubbed into the skin. This transdermal delivery mode supplies hormones to the body throughout the day by depositing in the underlying fatty tissue. By transdermal application through the skin with permeation enhancers, bio identical hormones are directly absorbed into the bloodstream and the patient can effectively bypass the first-pass effect wherein the hormone is metabolised in the liver to produce harmful metabolites. This alternative route of administration provides a more consistent and natural way to introduce medications into the body with minimal side effects, if any.

However, Chaturvedi emphasises, "Although bio identical hormones are natural and safe, they are still hormones, and need judicious monitoring, which makes the involvement of the physician in the treatment necessary. Unsupervised and inaccurate dosing can cause usual side effects as with any medicine. In therapeutic monitored doses the side effects are either very minimal or absent as compared to synthetic hormones."

One loophole is that as this therapy is not FDA approved, patients on this therapy are not covered by insurance. Apart from insurance, the cost of medication is also a bit higher than other therapies. According to Chaturvedi, a month's treatment costs thousands of rupees depending on the number of hormones that need to be administered and as the cost of the products depends on components included in the compounded prescription, it can vary from patient to patient. Therefore, there is no printed maximum retail price (MRP) on such products dispensed by pharmacies.

Parikh feels, "At this moment physicians should be the target audience for training. BIHRT is far more expensive than traditional hormones in use. Considering the need for use over many years with periodic estimations of levels of more than one hormone—in itself a costly proposition—they are not affordable to a person of average means."

What needs to be done

So far, BIHRT has been very popular in USA, Europe and other developed countries. More and more patients considered this option after the release of the Women's Health Initiative (WHI) study, which was conducted using synthetic hormones in women. This study was discontinued in between because of the increased incidence of stroke and cancer in the subjects using synthetic hormones.

Chaturvedi informs, "We are working hard to bring this therapy to the frontline medicine in India. The only way it can be available to common people is when more and more physicians share the same vision and there is more public awareness public about this alternative and safe hormone replacement therapy."

The art and science of compounding is not new in India and in due course of time, more and more people are becoming more aware about health. The cutting edge technology, where hormone deficiencies can be identified and corrected precisely by compounding natural hormones for individual patients needs, is phenomenal and is gradually being accepted by main stream medicine. With proper efforts, more and more physicians would be looking at BIHRT as an alternative to prevent age related disease and disorders and to improve the quality of life.

"The need of the hour is to enlighten the medical fraternity about the newly emerging science of bio identical hormones and, more importantly, to conduct authentic randomised controlled clinical trials on bio-identical hormones after obtaining ethical committee clearance and registration with Clinical Trial Registry of India," concludes Parikh.

suja.nair@expressindia.com