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Sex Hormones for You, Personally

Let’s take a look at the sensible replacement of an individual woman’s hormones at menopause.  Yes, this is a personal approach for one woman’s needs, not some “one size-fits all” protocol. We start by understanding normal physiology – “how it works” and apply modern science to find the best doses for you personally.  Our goals are success and safety.

To help you understand this better, let’s see what hormones do and what happens when we lose them.  I’ll explain why it is important to consider replacing them at menopause and why sooner is better.  We’ll see how that can – and should – be done.  If we’re going to do this, let’s do it the best way, one woman at a time!

Basics:  Puberty to Menopause

Hormones are little chemical messengers that change the way your body behaves. Sex hormones transform our bodies from those of children to healthy adults and allow us to reproduce the species.  Glands are collections of cells especially-designed to make particular hormones.  The output of these little hormone-factories is controlled by feed-back to the brain and glands themselves – the body stops making a hormone when it has enough.

What happens at menopause?  Levels of sex hormones fall and a woman’s body starts returning slowly to its original child-like state.  The early symptoms are described by Harvard’s Dr. Altman as “estrogen withdrawal”: Hot flashes; insomnia; mood swings and depression; “brain fog” (cognitive dysfunction), and reduced libido are some of the worst ones.  Some of these, like hot flashes, usually ease-off in time.  Other symptoms get worse: Menopausal women not taking hormones can enjoy an active sex life but according to Yale’s Dr Sarrel, participation falls from 90% at age 50 to only 10% of women aged 60.

After 5-10 years, women progress to what Altman calls “hormone deficiency” and their bodies show serious changes from lack of hormone support.  Their genitals return to a childish state, becoming thin, dry and fragile.  They lose muscle-tone and their waistline and bladder sag, permitting urine leakage as their hourglass figure becomes a bowling-pin.  Cholesterol goes up as does their risks of heart attack and stroke.  They lose bone calcium and risk fractures.  They are more vulnerable to colon cancer and arthritis.  Even the brain suffers: Their risk of dementia is increased and strokes can do more damage.

History of Treatments for Menopause

In the mid-1950s, hormone treatment for menopause became available and women were offered hope and relief from their dreadful symptoms.  There were no lab tests in those days and doctors gave estrogen replacement based solely on symptoms.  It took 20 years before they could see that oral estrogen replacement gave women uterine cancer; their uterine cells had needed progesterone to prevent cancer but hadn’t gotten enough.  This was an early lesson in the importance of balancing hormones!

The modern era of hormone replacement began in 2002 with the Women’s Health Initiative (WHI) study.  The WHI was a flawed study of a flawed practice.  Shockingly, its alarming claim that hormone replacement treatment (HRT) causes breast cancer – trumpeted by all the media – was not true!   In the final data analysis, the increased risk was not statistically significant!  Do you remember hearing that retraction?  Neither do I.

Good came of the WHI, though.  It revealed that our old methods of HRT hadn’t been the best.

  • It showed us the synthetically jacked-up progesterone (called “progestin”) we’d been giving to protect the uterus may increase women’s risk of breast cancer.
  • It showed us that hormone replacement should be started earlier rather than later.  The longer women wait to begin, the less they may benefit and the greater their risks.
  • It proved that women’s HRT had become so political that even scientists were unable to accurately report their data.

The WHI gave us impetus to re-evaluate and to re-invent HRT – and that is a great outcome.  The WHI and other research studies included huge numbers of rather diverse women, all treated exactly the same.  Alert physicians could see clearly that each woman needs to be treated individually.  With modern laboratory tests, we now have great tools to do this.

Individualized Hormone Replacement Treatment

With heightened awareness, then, we ask: “Who needs hormone replacement treatment?”  First, women with symptoms can benefit from treatment.  Their symptoms come from altered feedback and low hormones.  Secondly, we believe women with a family history of hormone-deficiency problems such as bone loss (osteoporosis) are good candidates for HRT.
Thirdly, the laboratory shows us women with lower hormone levels have greater risk for degenerative diseases.  This has become distressingly apparent in women treated for cancer by hormone-deprivation.  Healthy women with low hormones are headed for hormone-deficiency problems and the most specific preventative treatment is to restore those very hormones.

Of course, there’s more to this than just throwing hormones at women.  As we start to look at the art and science of skillful HRT, I think it goes without saying that we must use only biologically-identical hormones.  Among the many reasons for this, the laboratory can detect only bio-identical hormones and using the lab to evaluate our patients is a “key” to getting good results.

Please understand that “biologically-identical” is not the same thing as “natural.”  Estrogens in pregnant horses’ urine are natural but they are not identical to human hormones – and that makes them undesirable.  On the other hand, plant estrogen that has been modified to make it identical to human estrogen gives us excellent results – because it is identical!

Doctors must consider the age of each woman as well as questions like “do you still have your ovaries” and “when was your last period?”  Such simple things significantly influence our testing strategy and treatment doses.

After we’ve chosen to start HRT, the next obvious question is “with which?”  Some women need only one or another or the third sex hormone in order to achieve balance at desirable levels.  Most women need different amounts of several hormones – and we’ve learned balance is essential.  An important lesson we can infer from the WHI was that doctors shouldn’t recommend “rubberstamp” treatment.

Next, ask “how much?”  The WHI also used “one-size fits all” and showed us that wasn’t so successful.  When women take hormones, their body has to accept them, at least for a while, until it processes and expels them.  The bigger the dose, the more of that hormone the body has to deal with, for better or worse.  Since docs create and control patients’ blood levels by the dose they choose, they must ask: “What blood levels are desirable for this person?”  That’s a darned important question!

The answer to that question should settle a huge debate that’s been raging over 40 years – is HRT is good or harmful?  The “pro” group points to the terrible degenerative changes that follow years of low hormone levels and correctly argues that HRT is good.  Their opponents say HRT is bad, because the more estrogens women take, the greater their risks of cancers, blood clots and gallstones – and they are also correct.  The argument has been so fierce because both sides are right!  How can this be reconciled?

We need to invite a lateral-thinking solution. Just think like Goldilocks: If one extreme is too hot and the other is too cold, is there somewhere in the middle that’s “just right?”

What hormone levels give the best effects at the lowest risks?  We don’t know yet.  Some doctors avoid the question altogether by giving “low-dose” birth control pills. This plans move hormones from low to high and back again every month, perpetuating the menstrual flow.

Many Anti-aging and integrative doctors give women robust doses of all the hormones.  Their patients may have every-day blood levels so high they are normal only for the second half of their monthly cycle.  This is called the “proliferative” phase and cancer is uncontrolled proliferation; it concerns me – is cell growth over-stimulated?  Remember, the higher the hormone level, the greater the risks!

It seems safer to use lower doses – the least amount of hormones needed for our patients to feel well.  This begs the question: How much is that?  Perhaps Nature gives us some guidance.

Let’s ask, then: When in the normal monthly cycle do women feel best?  That second phase of the cycle is pre-menstrual, when many women don’t feel well – PMS, right?  Uncomfortable symptoms occur so often at mid-cycle that the Germans gave it a name: mittelschmerz, or “middle-pain.”  Oh, and who feels great when their menstrual flow is just starting?  When you ask lots of women, as I have, nearly all report feeling best in the days after their flow has stopped and before they ovulate – called “mid-follicular.”

First Steps – Progesterone and Testosterone

Delightfully, these follicular blood levels are rather modest and are relatively easy to reproduce.  To most doctors’ surprise, women can make ample amounts of progesterone and testosterone for themselves with a little over-the-counter (OTC) help.

First, we must supply tools (co-factors) to our glands’ enzymes that make sex hormones from cholesterol.  These tools are dietary nutrients but our food may not provide enough.  Supplements called “adrenal glandulars” provide them very effectively.  I’ve given some details at the end of this paper.

Secondly, partly-assembled sex hormones (precursors) called pregnenolone and DHEA can be taken orally to produce progesterone and testosterone.  Their safety – and the reason they are sold OTC – lies in the fact our body doesn’t have to use them.  They are a perfect example of an important principle: Give the body what it needs and it will often do the job for itself.

Both of these precursors bypass a “synthetic bottleneck.”  They replenish those people who by stress, exhaustion and failing or surgically-removed glands are not making enough of their own.  DHEA is two steps away from becoming testosterone and pregnenolone is just one step from progesterone – but whether our body takes those steps is completely its option.  Unless it is biochemically “drowned” with an overdose, it will simply get rid of what it doesn’t want to use.
How do we know we’ve given enough – and that the body has chosen to use it?  Right; we test the blood for hormones.  It is surprising how few women need to take progesterone or testosterone once they’ve started these OTC precursors.  I was even disappointed to learn that nearly all menopausal women need prescription estrogen.  At menopause, the particular enzymes that make estradiol just don’t work well (let’s skip that biochemistry, OK?).

Prescription Estrogen

Giving estrogens raises two key questions: Of the three kinds of estrogen, which should we give and how should it be taken?

To the first question: We should use estradiol, in the smallest amount needed to achieve our goals.  Estradiol is the most active form of estrogen and most efficiently gives us the effects we desire.  Why is there any debate?  There have been undesirable side effects of HRT.  Before blood tests showed us most of these ill-effects come from excessive dosing and high blood levels or unbalanced hormones, some doctors had worried that estradiol might be too strong.

These concerned physicians hoped the other two estrogens might add a mellowing influence.  In the name of balance, they advocated treatment with all three, as “Tri-Est,” in the proportions normally found in healthy people’s blood.  That turns out to have been unnecessary, even unwise.

One of them, estrone, is not harmless.  In fact, research shows a version of estrone (16 alpha-hydroxyestrone) is often associated with cancer and other trouble.  So, estrone was pulled out and Tri-Est became Bi-Est.  Recently, the FDA withdrew its permission to use the third estrogen, estriol and now, the continued use of Bi-Est is challenged.

Is the loss of Bi-Est a terrible shame?  Not at all; our body converts estradiol to estrone and that to estriol.  When you take estradiol, you’ll make the rest… and if estradiol is taken correctly, all three will balance.

So, when we use estradiol, how should it be taken?  For years, some compounding pharmacists had given us the right answer but it took the French to prove it: Estrogens should be absorbed through the skin.  What an odd way to take something into our body – why not by mouth, as we did for decades?

When we swallow estradiol, it is absorbed from the small intestine and travels in the blood to the liver.  Our liver normally disposes of unwanted hormones and it “chews up” the great majority of what we’ve swallowed.  Worse are the undesirable byproducts it “spits out”; these include that bad actor we just met, 16 alpha-hydroxyestrone.  These byproducts also competitively interfere with estradiol, so the 10% or so that has gotten in past the liver doesn’t work as well as it could.

Absorbing estradiol through the skin gets it into the bloodstream without first passing through the liver.  Women get the same blood levels of estradiol with just one-tenth the dose – and they get far fewer unwanted and possibly risky estrogen-breakdown products.  They get better results from taking far less estrogen and that is proven to be safer.

Risky Business

With this information, you are now ready to consider some difficult issues: Does even perfectly-crafted hormone replacement involve any risks?  Also, is there any person who ought not to take HRT?  Let’s take a careful look at the risks of cancer.

First, women who choose not to take HRT and are willing to accept the degenerative changes of “hormone deficiency” can still get cancer of the breast, uterus and other estrogen-responsive tissues.  In fact, about 10% of women who take no hormone replacement will even-so develop breast cancer.

Secondly, estradiol does not cause cancer.  Estrogen may encourage cancer growth, though.  Our body occasionally produces cancer cells and our immune system kills them, the way a gardener pulls up weeds.  A tumor forms if cancer cells proliferate and grow faster than the immune system can destroy them.  Estradiol increases the chance of a tumor by “fertilizing” some cancer cells and speeding up their growth.  So, yes: People taking estrogen replacement are slightly more likely to get breast cancer.  But wait: Estradiol does something more – with a protective effect!

Estradiol causes breast cells to mature and assume their adult form.  Estradiol has the same effect on breast cancer cells, making them better-differentiated and therefore easier to cure.  This really adds to the complexity of assessing the risk of HRT.  Women who take no estrogen replacement get comparatively fewer cancers – but those they produce are more likely to have anaplastic or primitive cell types with a worse outcome.

There is a final cancer trade-off that must be mentioned.  Women who are not treated with HRT get significantly more colon cancer.  What’s worse, colon cancer is more often fatal than breast cancer.  Because breast cancer is more common, it is a bigger killer of women but colon cancer is definitely the deadlier of the two.  A woman’s risk of colon cancer should be a factor in her decision about using HRT.

Who Should Not Be Treated With HRT?

Breast cancer runs in some families.  While Science has identified some “cancer-genes,” these explain less than 20% of family-related cancers.  Women with a strong family history of breast cancer ought to seriously consider avoiding HRT.  What’s strong?  Well, one patient, her mother, her sister and her son had all had breast cancer; that’s “strong!”  However, if your grandmother got breast cancer at 80, your risk is probably not increased.  I’ve heard a Smart Guy say that breast cancer is so common in the US that you may be at no greater statistical risk even if your aunt gets it.

A woman’s decision to start HRT should be the result of counseling with her physician or practitioner.  There can be no guarantees.  If you feel too anxious about the risks to take it with peace of mind or a true sense of comfort, then don’t start it!  Follow your feelings as an “inner guide” and respect them.

Final Thoughts

Well, let’s say that taking nutrition and precursors and a little dinky bit of transdermal estradiol have achieved normal blood levels – you and your Doc ought to be in hog heaven now!  But – what if you are not feeling fantastic?  Here are a few considerations for menopausal-age women:

Lots of other problems appear during our forties and fifties, when menopause sets in.  Thyroid trouble is one of these; up to 20% of menopausal women have thyroid trouble.  Insulin resistance also becomes a really big problem at this age and the hormone changes of menopause just seem to make it worse.

Insulin resistance alters women’s enzymes and they make too much dihydrotestosterone (DHT) – the strongest masculinizing hormone.  When this happens, even modest amounts of DHEA or testosterone can “go wrong” and cause acne, hair growth on the face and body and male-pattern baldness.  Saw palmetto in rather big doses can give excellent relief for this particular form of hormone imbalance.

The combined effects of menopause, thyroid trouble and insulin resistance can result in prodigious weight gain.  This significantly predisposes a person to the sleep apnea syndrome.  However, even without obesity, sleep apnea becomes rather common at mid-life.  It can steal our vitality while we sleep and we may never realize what is causing the problem.

Hormone replacement can alter thyroid hormone activity – and vice-versa.  Estrogen and thyroid hormones have “cross-talk” in the cell nucleus.  Occasionally, thyroid treatment must be adjusted after starting HRT – just as we may need to increase estrogen doses after going on thyroid treatment.

Estradiol is broken down to estrone, as we’ve seen.  Estrone can be metabolized to harmless versions or that trouble-maker 16alpha-hydroxyestrone.  Your practitioner can order a blood test to monitor this through LabCorp and it’s usually covered by insurance.  If an imbalance is found, the nutritional supplement Indole 3 Carbinol  may correct it – Metagenics makes a good one.


Sixty years ago, researchers made hormones available to relieve the suffering of menopausal women.  We are now learning how to use these with precision and skill.  We are guided by research, which has provided important data and fostered new concepts.  We are aided by newly-available and remarkable laboratory technology.  This “new endocrinology” helps us maintain the health and restore the joy of life to an amazing number of people with a minimum of risk.

See GMA Articles and Podcasts on Bio-identical Hormones