By Marios Kyriazis, M.D.

Until a few years ago, the use of non-synthetic hormones was confined to only a small number of patients treated in specialist centres. The fact is that non-synthetic (bio-identical) hormones have been around for many years, but most mainstream physicians are still unaware of their benefits.

These mainstream physicians treat their patients with synthetic hormones, i.e. hormonal compounds created artificially in the laboratory. These hormones may indeed have a good therapeutic potential, and have helped millions of people across the world. The problem is, because their chemical structure is artificial, they may not have the full range of benefits necessary for optimal health. In addition, these synthetic compounds have a high risk of side effects, precisely because they don’t interact naturally and smoothly with the body. Synthetic hormones are specifically manufactured to be different than the body’s own hormones. One reason for this is that synthetic hormones can be patented and used commercially by only one manufacturer who reaps all the profits.

By contrast, hormones that are the exact replicas of our own body’s hormones are called ‘bio-identical’. These are natural compounds which are adjusted in the laboratory in order to make them look and act exactly as your body’s own hormones. In this respect, bio-identical hormones are not necessarily ‘natural’. They are taken from natural sources but are then modified in the laboratory to make them resemble the structure of a human hormone. By the way, it is also worth remembering that ‘natural’ does not always imply that a particular compound is safe. That said bio-identical hormones are considered to be a much better alternative to synthetic ones, if used correctly by a specialist practitioner.

The most commonly used bio-identical hormones are estrogens and progesterone. These are obtained mostly from soya beans. Another bio-identical hormone, testosterone, is usually obtained from wild yam. Other bio-identical hormones are DHEA, melatonin, thyroid hormone, androgens, pregnenolone, growth hormone and variations of these.

Menopause Treatment

In my practice, I use several of the above compounds, usually in combination with other nutrients and herbal supplements. With regards to the menopause, my usual advice for women with mild symptoms (such as hot flushes, sweating, low mood, tiredness, sexual disinterest, and poor sleep) is to try herbs and plant remedies first. Examples of these are isoflavones, either in tablet form or from foodstuffs such as soya and red clover. In addition herbal remedies such as black cohosh, evening primrose oil and dong quai (a Chinese herb) taken in combination, may be helpful in reducing the symptoms of the menopause.

If symptoms are severe and interfere with the patient’s everyday life, then it may be time to try hormone replacement. Most women I see are initially prescribed synthetic estrogens by their own physician. But many experience side effects such as weight gain, fluid retention and nausea. Also, the risk of breast or other cancer is relatively increased with the long term use of synthetic hormones. For these reasons, I recommend bio-identical estrogens and progesterone treatment when relevant. These hormones have other long-term benefits like protection against osteoporosis, heart disease and age-related brain problems.

A major problem associated with the menopause is depression. This is caused by fluctuating or sustained estrogen deficiency and can thus effectively be treated with bio-identical estrogens (1). Indeed, as you can see from the example in Box 2 (case studies) a typical menopausal patient will suffer from some degree of depression, which usually improves after bio-identical hormonal treatment.

Another menopausal problem is memory loss. There is a debate whether any hormonal treatment (synthetic or bio-identical) can benefit memory loss (2) but in my experience most women who take bio-identical estrogen also report that their memory generally improves.

Bio-identical hormones are usually given transdermally, meaning that they are applied directly on the skin, rather than used in tablet form. The benefit of this is that the hormone by-passes the bowel and the liver (where it is neutralised), so it stays active for longer. An equally beneficial way of using bio-identical hormones is by sublingual spray, i.e. spray used under your tongue. This ensures a good absorption rate, with suitable amount of hormone reaching the tissues through the blood stream, by-passing the liver.

On many occasions, menopausal women will require additional bio-identical hormonal support. This can be achieved with hormones like DHEA, pregnenolone and thyroid hormone, depending on the results of individual hormone blood or saliva testing. In addition, it is possible to use bio-identical growth hormone (GH), as opposed to synthetically produced GH.

The aim here is to provide more energy and vitality, and boost the actions of estrogens in general. This can also be true of middle aged and older men, who may need extra support for their immune, muscular and skeletal systems.

Research performed at the Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy confirms that bio-identical estrogen works in two separate ways:

• (a) It interacts with special cell receptors, such as ER-beta 1 or ER-beta 2. These receptors recognise specific chemical configurations of the estrogen molecule and permit it to act on the cell, helping it to stimulate other enzymes and compounds that result in a reduction of the clinical symptoms of the menopause.



• (b) Bio-identical estrogens are able to activate the body’s own production of estrogen. In other words, the bio-identical estrogen molecule is not only active on its own right, but can also stimulate the ovaries and other tissues to further produce estrogens, thus optimising the amount of estrogens available (3).

The three different types of estrogen

Estrogen hormones exist in three main types: estone, estradiol and estriol. Estrone (E1), levels are high in post-menopausal women (whereas the other two types are low, so the overall effect is a net deficiency of estrogens). Estrone is considered to be a weaker variant of estradiol (see below) but its concentration has to be balanced according to the levels of the other two estrogen types. Estrone is usually released from fat tissue, and this is one reason why menopausal women tend to put weight on: it is a natural reaction of their body which tries to increase its fat reserves so that to hold more estrone. This can then be made available to the body, at a time when natural production of estrone decreases.

Estradiol (E2) is the second and main type of estrogen produced by the ovaries, but becomes deficient during the menopause. Estradiol is usually active against several symptoms of the menopause such as night sweats and hot flushes. It works particularly well when administered as patches, creams or under the tongue. The reason for this is that it avoids the risk of being prematurely inactivated by the bowel and the liver.

Finally, estriol (E3) is quite a weak type of estrogen. Its concentration rises during pregnancy, but plummets during the menopause. Estriol is active in protecting the female sexual organs (vulva, vagina) and also the bladder, reducing the incidence of cystitis.

These three types of estrogen are commercially available either separately, or in combinations of two, or all three. For example, a preparation called Biestâ contains 80% estriol and 20% estradiol. Another preparation, Triestâ, contains 80% estriol, 10% estradiol and 10% estrone. A third called Esnatriâ contains 90% estriol, 7% estradiol and 3% estrone.

Other Bio-Identical Hormones

Progesterone

Women produce progesterone from their ovaries and adrenal glands throughout adult life. Although progesterone is generally considered to be a ‘female’ hormone, it is also produced in the testicles and adrenal glands of men. Progesterone has a range of actions, from modulating the reproductive cycle to protecting the brain and improving mood. Bio-identical progesterone is available in cream, skin patches or oral spray. The latter is an ideal form of delivery of the active hormone, as it enters the blood stream almost immediately. The majority of my patients who use bio-identical estrogens are also on progesterone spray.

Testosterone

This is the typical ‘male’ hormone responsible for maintaining energy, strength, libido, bone tissue and muscle mass. As with the case of progesterone, testosterone is also present in women but at lower concentrations. Men over the age of 45-50 who complain of depression, tiredness, loss of sexual desire, impotence, or muscle weakness are increasingly treated with bio-identical testosterone, usually with good results. However, it is important to be under the supervision of a knowledgeable physician, who will perform regular tests aimed at establishing the concentration of the hormone.

DHEA

The levels of the hormone de-hydro-epi-androsterone (DHEA) usually fall with age, resulting in a variety of physical and mental symptoms such as muscle weakness, immune system impairment and memory loss. I normally use DHEA in association with other bio-identical hormones particularly in middle aged women and older men. But this must only be used after initial blood or saliva test are performed, and then the dose is titrated according to clinical and laboratory response. The usual dose is around 25 mg daily, but some women may need half this amount.

Treatment with bio-identical hormones is heavily based on laboratory measurements of the patient’s own hormonal situation. Once the initial laboratory test has been performed, the patients takes the hormonal therapy prepared specifically for her needs and then the dose is adjusted according to clinical response or/and further laboratory testing. Bio-identical hormonal treatment is not something you should take lightly, and without medical supervision. Also you or your physician should ensure that you are using products from reputable, established suppliers who may be able to provide background information and support when necessary.

Safety issues

Some doctors doubt that bio-identical hormones are safer than synthetic ones. These professionals believe that, in principle, the two types of hormones are bound to have the same risks and side effects. For example, two years ago, researchers from the Columbus Regional Drug Information Center, Columbus, USA, performed a comprehensive review of existing research about both synthetic and bio-identical hormones. They concluded that there was little available research to suggest that any treatment method had an advantage over the other. They did find however those bio-identical hormones may indeed reduce some of the symptoms of the menopause (4). By contrast, others say that the bio-identical molecule is recognised by the body as a ‘friendly’ molecule and so it does not increase the risk of any side effects. These doctors believe that if bio-identical hormones are used in recommended doses, under medical supervision and not for long periods (say, over 10 or 15 years) then the risk of side effects is reduced.

However, do have in mind that bio-identical hormones are not perfect. It may be necessary to adjust the dose, or stop the treatment completely, either because it is not fully effective or because of side effects. But in my experience I have not yet encountered anybody who reported any significant adverse effects after using bio-identical hormones. A relatively common problem is that the initial recommended dose proves not strong enough and some of the symptoms remain. In those situations, it is necessary to increase the dose or add other products to maximise the effect.

Case study 1

Marie is a 42 year old stock market broker from Europe. She suffered from night sweats, depression, low energy and loss of libido for about a year, despite following a healthy lifestyle and taking several menopausal support remedies (black cohosh, dong quai and soya). After evaluation of her estrogen levels it became obvious that she needed hormone replacement. I started her on a combined bio-identical estrogen preparation called Esnatriâ (containing estriol 1.8 mg, estradiol 0.14 mg and estrone 0.06 mg) together with Transmistâ spray which is a newer form of bio-identical progesterone. She noticed an immediate initial improvement within two weeks. She continued to improve over a period of three months, but then she reached a plateau. Her depression and sexual problems disappeared completely, but her night sweats continued in a less severe form. I advised her to double her original daily dose and this ensured that her symptoms improved even further. Continued laboratory testing confirmed that her levels remaned within normal range.

Case study 2

Jane, a 50 year old solicitor from London, has been on Esnatriâ (triple estrogen) cream for over two years. While she experienced positive benefits during this period, she started noticing that her daily dose was not sufficient to completely relieve her menopausal symptoms (particularly tiredness and sexual disinterest). She was not keen of increasing the dose of her triple estrogen cream and she did not experience any added benefits following treatment with soya or red clover. She eventually decided to add cobalt supplements (cobalt is a mineral which helps estrogen work more effectively in the body), in addition to her cream. She was also started on a daily dose of 25 mg DHEA. This worked like magic and, at the time of writing, remains symptom free.

Quotes from eminent physicians and researchers

Dr. P. Watt from the Joseph F. Sullivan Center, Charleston, USA says: “With an unprecedented number of women reaching midlife, the impact of menopause has become a significant public health issue. Recent findings have left women and practitioners questioning traditional hormone replacement therapy and searching for reasonable alternatives. Growing numbers of women in this country are choosing to use natural progesterone and estrogen to treat symptoms of menopause (5).

Dr. Jonathan Wright from Tahoma Clinic says about bio-identical hormones: “While no therapy is completely risk free, in approximately 20 years we've observed very, very few adverse effects. Bio-identical hormone therapy is far and away less risky than the use of horse urine and progestins, which women should surely avoid (6).

Dr. M.L. Stefanick from the Department of Medicine, Stanford University in California comments: “By 2001, approximately 15 million US women were using estrogen therapy, with or without progestins. The 2002 Women's Health Initiative report of greater harm than benefit of combined estrogen plus a progestin resulted in a precipitous decrease in estrogen and progestin use and a serious re-evaluation of menopausal hormone therapy, as well as increased interest in alternative approaches to managing menopausal symptoms, including use of bioidentical hormones” (7).

Finally, Drs. J. McKee and S. Warber from the Family Medicine Department, University of Texas, remarked: “Hormone replacement therapy (HRT) has been the mainstay of therapy for menopausal symptoms (but) women and their physicians are seeking alternatives that do not carry the risks associated with HRT. Exercise has been shown to help some women with hot flashes, as have relaxation techniques and deep breathing. Dietary changes to incorporate whole foods and soy are thought by some to help with menopausal symptoms, and are recommended because of a positive impact on heart disease and obesity; soy isoflavones may also help with menopausal symptoms. Botanicals such as black cohosh and red clover have been shown in some studies to decrease severity and frequency of hot flashes. We recommend that HRT be prescribed when other measures have failed to adequately control symptoms. Bioidentical hormones are preferred in our practice”. (8).

Conclusion

Bio-identical hormones are now a modern and well-researched concept. These are generally believed by many health practitioners, to be a much better alternative to the synthetic hormones, and many more physicians are becoming increasingly confident in using them.

Compared to just 10 years ago, bio-identical hormonal treatment has come a long way, and it is now considered to be a cutting-edge mainstream therapy.

References

1. 1. Douma SL, Husband C, O'Donnell ME, Barwin BN, Woodend AK. Estrogen-related mood disorders: reproductive life cycle factors.ANS Adv Nurs Sci. 2005;28(4):364-75.
2. 2. Kok HS, Kuh D, Cooper R, van der Schouw YT, Grobbee DE, Wadsworth ME, Richards M. Cognitive function across the life course and the menopausal transition in a British birth cohort. Menopause 2006;13(1):19-27.
3. 3. Cappelletti V, Miodini P, Di Fronzo G, Daidone MG Modulation of estrogen receptor-beta isoforms by phytoestrogens in breast cancer cells. Int J Oncol. 2006;28(5):1185-91.
4. 4. Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy: a review. Menopause. 2004;11(3):356-67.
5. 5. Watt PJ, Hughes RB, Rettew LB, Adams R. A holistic programmatic approach to natural hormone replacement. Fam Community Health. 2003;26(1):53-63.
6. 6. Wright JV. Bio-identical steroid hormone replacement: selected observations from 23 years of clinical and laboratory practice. Ann N Y Acad Sci. 2005;1057:506-24.
7. 7. Stefanick ML. Estrogens and progestins: background and history, trends in use, and guidelines and regimens approved by the US Food and Drug Administration. Am J Med. 2005; 19;118(12 Suppl 2):64-73.
8. 8. McKee J, Warber SL. Integrative therapies for menopause. South Med J. 2005;98(3):319-26.