In addition to becoming feminized on your own, particular, personal terms, the basic objective when seeking feminizing hormone therapy should ideally be to improve the risks to benefits ratio of these hormones, in other words to minimize risks and side effects while at the same time tailoring the rapidity and effectiveness of feminization so as to match the desires of the individual patient.

Precise hormonal therapy

For numerous consumers this means maximizing both the degree of effectiveness and the rapidity of onset of feminization, but many trans-women request a more conservative approach, either from a desire to be extra-careful or because they are not committed to going all out, for either social or financial reasons, as is their personal prerogative. 

The hormonal paradox

Many, even those who are practitioners assume that weaker hormones means safer hormones, but this isn’t true at all.  Oral estrogens are far less effective at the task of feminizing the body than are non-orals, yet ironically, despite their relative ineffectiveness they are the most side-effect & risk prone, particularly in terms of clotting risks, gall bladder disease, high blood pressure, elevated triglycerides & pancreatitis.  Despite this, oral estrogens are still the most frequently prescribed hormones for trans-women.  This implies that many prescribers lack knowledge or expertise in the area of hormone therapy, particularly in terms of trans-care, where the unusually high hormonal doses required for feminization put people particularly at risk when inexpertly administered, as is so often the case. 

It follows that the first step along the trans-pathway should entail the absolute avoidance of oral hormones.  This also means seeking one's hormonal therapy from a quality source involving true hormonal experts well qualified to administer feminizing hormones in a responsibly supervised, personally tailored manner, using a rational, scientific basis for their choices & their actions instead of being crudely empirical.

Your doctor

The kind of hormonally qualified physician who has been formally trained in the nature and the use of hormones is either a clinical endocrinologist or a reproductive endocrinologist.  A clinical endocrinologist is someone who, having been fully trained for 3 years in the field of internal medicine then serves a 2 year sub-specialty fellowship in endocrinology & metabolism.  This usually involves both clinical training aimed at the diagnosis and treatment of hormonal disorders as well as training in the use of the clinical & research laboratories and in the pursuit of clinical research. 

A reproductive endocrinologist on the other hand is a gynecologist with special interest & extra training in the hormonology of women’s health, particularly concerning the sexual hormones of the ovaries.  This specialized gynecologist generally knows far more about hormones than the general OB/GYN. 

Some practitioners, even though they have never received formal training in endocrinology or in reproductive endocrinology, perhaps not even in internal medicine or general gynecology, may develop a particular interest in hormone therapy & portray themselves as self-appointed hormonal experts. For some of them, this interest seems superficial and unimpressive, based on what I think of as pop-endocrinology.  Many of these can be found in the field of alternative medicine, calling themselves ‘naturopaths’ & ‘anti-aging’ gurus.   On the other hand some physicians of high intelligence & intellectual honesty who adhere to the scientific method become significant experts in the hormonal field despite their lack of formal training, by virtue of assiduous study, sincere scholarship & on the job experience.  They could considerably deliver feminizing hormones in an acceptably precise manner, in contrast to the slap-dash approach so prevalent amongst those marching under the banner of 'bio identical hormone therapy'. 

What are hormones?

Hormones are free floating agents carried passively by the ebb & flow of our circulatory tides over both short and long distances, while existing in infinitesimally tiny quantities.  Considering the nano-scale on which they exist, the biological impact of hormones at the macro level on both mind & body is absolutely staggering.  These chemicals, despite being present in only trace amounts, can dramatically alter your life, physically & mentally for better or for worse.  Now if I had a firearm in my home, I believe I would ensure that only weapons’ experts could gain access to it, and the same goes for toxic chemicals, such as rat poisons, which should only be handled by experts.  But hormonal treatments can be just as dangerous, particularly in the hands of licensed amateurs.  That is why hormonal expertise is so very important, yet locally I find opportunistic surgeons, general practitioners & dermatologists for example, not only lacking endocrine training but even lacking training in general internal medicine, yet who casually & liberally prescribe & distribute hormones to the trans-community.     

A loaded gun

Let me illustrate the depth of people’s widespread ignorance with regard to hormones, including even those who happen to be licensed professionals.    Most physicians still consider hormones as chemical messengers, but that is not the case.  Instead hormones are mobile chemical agents that either activate or inactivate precisely matching hormone receptors resident at the cells of their target organs.  Once activated, these receptors in turn initiate the playing of prerecorded messages already resident within their target cells, as opposed to carrying the messages freshly there themselves. And they do this by interacting with their receptors in a fundamentally physical rather than a chemical manner.

There are two basic types of hormones in existence; large ones and small ones. The large hormones are peptides comprised of polymeric sequences of amino acids and they are too large and far too ionized to chemically penetrate the outer lipid membranes of their target cells. Instead they meet up with their hormone receptors as they encounter them embedded within the outer surfaces of their target cell membranes.  Once activated these receptors now initiate transducer sequences having influences that are rapid and short-lived.

The small hormones

The body also produces small hormones, including the thyroid hormones and the steroids.  Steroids are single molecules rather than polymers & because they are fat soluble they can penetrate the cells’ lipid membranes thus permitting them easy access to the target cell interior, including the nucleus & its chromosomes as well as their heavily protected genetic code. 

The steroid group of hormones

The adrenal cortex produces cortisol as well as steroids known as adrenal androgens, notably DHEA.  During pregnancy the placenta produces large quantities of progesterone. Progesterone is also prominent in non-pregnant women, but only during the second half of each menstrual cycle. Testosterone is produced by the testicles in men and by the ovaries in women.  Although ovarian production of testosterone is considerable, much of it is promptly converted into estradiol, thus averting physical masculinization.  Never the less, a significant quantity remains in the unconverted state.  Far from being a biological oversight or incidental spillover however, testosterone of ovarian origin in the genetic woman serves a natural, health-promoting role both physically & mentally, one that many practitioners ignore, such that testosterone deficiency in women is associated with loud expressions of anxiety, depression, sexual dysfunction & fatigue, as well as a probable increase in breast cancer risk.

The androgen-estrogen interplay

First let it be said that estrogens are not converted by the body into androgens such as testosterone; conversion only goes the other way.  In many non-glandular bodily organs including the liver and the fat cells as well as the hypothalamus, when testosterone arrives at these sites it is converted to some considerable degree into estradiol and also into a highly androgenic hormone called DHT (the hormone behind hirsutism and baldness). However DHT in turn is converted into a weak androgen that selectively stimulates the beta type of estrogen receptor, thus significantly reducing the risk for breast and other cancers.  In some trans-women after years of feminizing hormone therapy and particularly in those whose testes have been removed during gender reassignment surgery, testosterone dips down to a level below that which is normally present in healthy genetic women, leading to depression, suicidality and loss of sexual interest. It follows that low dose testosterone therapy may sometimes be necessary & even highly beneficial in trans-women. 

Androgens

While people associate androgens with masculinity, I see them more as hormones of aggression, whether physical or sexual.  It is the number of carbon atoms in their molecules (19) that defines these hormones as androgens rather than any male or masculine functional connotations.  Indeed some androgens are masculinizing while others are not.  For example the steroid hormone DHEA is the most copious androgen in the body, being produced in the adrenal glands, the ovaries & the testicles.  Yet DHEA along with its breakdown product DHEAS have little androgenic hormonal effect per se, although they do have some indirect hormonal impact due to their conversion into both estradiol & testosterone.  When patients consume DHEA supplements they will often experience neuro-stimulatory effects causing them to insist that it is really beneficial as a hormonal therapy.  However these energizing effects are unrelated to hormone action.  In actuality these brain-based changes reflect a thoroughly non-hormonal effect exerted directly on the brain; specifically by influencing the neurotransmitter system involving glutamate. This effect is similar to that of Ritalin, the drug used in ADD patients. 

Male versus masculine

We really shouldn’t call testosterone a male hormone; after all it is also normally present in women. I prefer to think of testosterone as a hormone of masculinity & aggression, rather than a uniquely or particularly male-associated hormone.  Instead testosterone is a hormone that both masculinizes & defeminizing us. Thus masculinizing hormones make the breasts shrink whereas feminizing hormones support breast development. It follows that removing the testes may de-masculinize a person, but they do not feminize her. And feminizing drugs such as estrogen and progesterone, rather than simply de-masculinizing the body directly, also do so by switching off the brain drivers that activate the testes to produce androgens.  When attempting to feminize the trans-woman therefore, it is important to administer sufficient feminizing hormone as to effectively generate a chemical castration.

Progesterone & the progestins

The natural hormone progesterone is generously present during pregnancy and during the second or luteal phase of the normal menstrual cycle. At that time it is actually present in considerably larger amounts than are the estrogens. When administered orally, progesterone is converted by the liver into derivatives such as allo-pregnanolone, which has little or no hormonal effect per se but is a mind-altering chemical with powerful sedative, anti-seizure and pro-depressant brain properties.  Synthetic progestins are also produced commercially, some of them androgenic, others neutral and a few even anti-androgenic. Spironolactone is an anti-androgenic progestin as is cyproterone acetate.  Practitioners of alternative medicine remain heavy promoters of progesterone use in genetic women.  However it is now clear that progesterone and progestins, rather than estrogens are the real agents that increase breast cancer risk. However in transgendered male to female patients the risk of breast cancer is so small that the potential for progestin -induced breast cancer remains exceptionally low.

The estrogens

Of the progestins, only a single hormone known as progesterone occurs in nature but there are many synthetic progestin. In contrast there is no single hormone known as estrogen, whether existing in humans are even elsewhere. Instead there is a broad group of naturally occurring estrogenic hormones, some typical of humans, others occurring in other animals such as mares, and synthetic estrogens also exist, such as DES. This complex group of disparate hormones is not defined on the basis of its feminizing effects but rather on the basis of the number of carbon atoms it involves.  Far from being uniquely feminizing in their influences, the estrogens can generate either feminizing or defeminizing influences in the human body, sometimes even being palpably feminizing at one target area while defeminizing at another.

Human estrogens

Three estrogens are produced naturally in humans.  Prior to menopause the ovaries produce estradiol which is the principal natural estrogen of younger women.  In conjunction with progesterone, this hormone fuels development of the female sexual characteristics such as breasts, body shape and fat distribution as the prepubescent female develops into a mature, fully developed woman. As opposed to trans-formation we might call this cis-formation. When administered orally, estradiol passes through the liver and is massively converted by it into estrone. Estrone is the principal naturally occurring estrogen of older women whose ovaries are no longer estrogen-producing. The third human estrogen, known as estriol is a weak estrogen present in large quantities during pregnancy.  It does not appear to have any useful role in the treatment of menopausal women or trans-women, despite the marketing efforts of those selling the concept of so called ‘bioidentical hormone therapy’.

Some plants produce phyto-estrogens and the useful ones appear to be predominantly defeminizing rather than feminizing in their actions as well as being anti-cancerous.  Finally the synthetic estrogen known as ethinyl estradiol is present in birth control pills. Taken orally and passing first through the liver, ethinyl estradiol significantly increases the risks for clots and therefore for heart attacks, strokes, pulmonary emboli and sudden death. It should therefore be urgently avoided in transgendered patients where the dose of this synthetic hormone would need to be dangerously high to generate feminization. Recent studies show that young women taking birth control pills experience a significant yet generally ignored increase in the risk for depression.

Brain and immune system as sex hormone targets

Now that the physical nature of the sexual hormones has been clarified & common misconceptions have been made clear, there is only one other major factor to consider.  The vast majority of people, whether lay or professional, perceive the sexual hormones as being exclusively sexual in their influences, & they are emphatically wrong.  Similarly a sexualized approach to trans-gender medicine is the wrong way to go.  We don’t treat transsexuals or transgenereds or whatever you want to call this group of natural people, we treat people, normal though variant members of the human race.  That’s right, these people are just as normal as are homosexuals, and neither homosexuality nor trans sexuality is sinister or a disease process, so get over it!

Getting back to the sexual hormones, they clearly have a massive influence on the body at large as well as the mind in terms of its cognitive & emotive functionalities, in a way that has nothing to do with sexuality or reproduction.  Furthermore these non-sexual influences operate not only via the standard, sexual, genome-altering mechanism which is slow, sluggish & lingering, but also via extremely rapid, brief & evanescent mechanisms that are quite specific to the brain & immune/inflammatory targets & thereby the mind.  

Hormone balances

It follows that the rules of engagement for the sexual hormones are radically different to those officially accepted, rules that still erroneously dominate the field of trans-care.  And this is why precision is such an important component of trans-care.  By precision I mean not only precise dosing but precise patterns of delivery, distribution & elimination.  Elimination is terribly important because individuals vary widely from one to the next in terms of their rates of excretion of estrogens.  So a one size fits all approach to transgender HRT makes little or no sense.  And the therapeutic balance chosen between estrogen & progesterone dosages also matters immensely, varying from patient to patient and depending also on which other drugs they happen to be consuming, drugs that may alter the liver’s rate of hormone excretion. 

Hormone patterns

Beyond hormonal balancing there is the matter of hormonal pattern, whether stable or erratic & whether characterized by many dips & surges or by more stable patterns.  Many important medical conditions can be instigated, sustained or amplified by erratic hormone levels or by unsuitable disturbances in the balance between the hormones, so this idea of precision is critical to obtaining a safer yet more effective source of feminization through the auspices of hormone therapy. 

Why precision greatly matters

So precision means exactitude; in dosage, in hormonal balance & in dynamic pattern, in contrast to the slap-dash approach so often seen with trans-HRT.   Why this urgency?  Because, as we already pointed out, the brain & the immune/inflammatory system are not only extremely sensitive to sex hormones, their balances & their patterns, but their influences are mediated by a different mechanism involving not only slow but also super-fast processes.  It follows that crude hormonal therapy might fuel mental and inflammatory problems, & most of us are by now familiar with the frequent mental problems including severe hunger, weight gain, mood swings, anger, depression and the erratic, irrational behaviors, bordering on psychosis, of many patients when they use some of the illegal injectables such as Perlutal.  
In contrast, precisionHRT can deliver dramatic mental benefits.  Estrogen protects genetic women from schizophrenia, psychosis & bipolar disorder, and it reduces depression.  Both genetic & trans-women with a history of these kinds of mental problems will often improve dramatically when administered precision hormone therapy, reducing their needs for mind-altering drugs.  

Precision is what we focus on at O’Dea Medical Hormones, for our transgendered patients as well as those seeing us for the treatment of hormonal imbalances, the menopause or hormone-sensitive problems involving mind & brain that show resistance to psychiatric therapy. 

Other resources

There are other resources to which you can refer for more details about hormonal therapy.  For example we have a site called precisionHRT.com serving our menopausal patients which goes into considerable detail on the subject of optimalizing hormone therapy.  It complements this site without being repetitive.  And mindhormones.com is our site that reviews the massive links running between sex hormones & the mind.  Judicious hormonal modulation may often aide in the treatment of so-called ‘mental’ illnesses, particularly those that are resistant to standard therapy.