About Menopause

 

Why I’m Interested

Getting into men’s and women’s hormones was never my intention. It happened  as a result of several simultaneously occurring circumstances. The first of these involved my own daughters. The second was the result of working with the neuroendocrine mechanisms for making new brains cells after a stroke, neurogenesis. The third was the fact that all my 4 sisters-in-law hit menopause at the same time, the cumulative effect of which severely altered my own personal quality of life.

An endocrinologist friend helped get me started with my daughters’ care, along with my good friend, Dr. Roby Mitchell. My level of understanding of the brain and receptors and neurotransmitters and hormones gave me a great starting point. I figured that I had a Ph.D. in neuropharmacology, a Masters in human development and biostatistics, by Heaven, if no one else was interested in fixing my girls, then I’d better learn how to do it. From those starting points years ago, I began reading 3 or 4 books a week and hundreds of research papers…and I still do.

Needless to say, all this work opened up an enormous body of science to me that I found very disquieting. Much of the research from outside the U.S. for the past 20 years had demonstrated unfortunate potential consequences from equine estrogens, possibly the largest profit product of the American pharmaceutical industry in history. These unfortunate potential effects were later confirmed by the Women’s Health Initiative in 2002. It made no sense to me why, if we knew how to make estrogens that were exact copies of human estrogens, we would want to give women horse estrogens that were suspect for safety. After all, in neuroscience research we work with exact copies of the neurotransmitters if at all possible. Then I learned that anything that occurs in nature cannot be patented, but if the molecule is altered somehow, it can be patented. It became clear that there would be no profit in naturally occurring estrogens, and therefore no incentive to produce and promote a drug that any competing company can make. 

So my personal motivations were to fix my family members and to buy myself some peace under my own roof. In the neuroscience sections, you will see how much of the hormone data was already a part of my research involving the brain recovery from stroke and traumatic injury…(a concept not too distant from being married to a menopausal woman with 4 menopausal sisters.) Dr. Roby Mitchell had warned me that most doctors don’t understand women’s hormones and the intricate interactions of the thyroid and  adrenal glands and the pituitary and the ovaries. He was right!! And I found out why. It’s difficult!! It requires long clinic visits and lots of “doctor brain time” to make sense out of each individual’s symptoms and lab values and formulate a logical treatment plan. It cannot be done for the $30 that insurance companies pay to see a patient, so most doctors are not interested.

So let’s get started.

Currently, most doctors are recommending that women can use any hormone replacement at its lowest available dose for five years, if they absolutely must have something to control their symptoms. That includes all the equine estrogens as well. I disagree with this management. First, who decided that after 5 years a woman’s body no longer needs any estrogen? I can find no hard science that demonstrates a woman’s risk goes up 5 years into menopause if she stays on hormones. Secondly, the basic finding of the WHI study was that the use of PREMPRO resulted in increased strokes and heart attacks and breast cancer, not 17-beta-estradiol, the natural ovarian estrogen….and a woman’s body has been exposed to this estrogen for some 35-40 years from puberty to menopause without untoward effects, at much higher levels that would be encountered by the body in a hormone replacement protocol. So where did the “5 years” come from? Perhaps that’s when the risk of all the side effects from PREMPRO goes up. For more insight into these issues, go to the “Truth About Estriol” section in this website.

There are, in fact, many benefits from estrogen and progesterone replacement that are as yet poorly understood by doctors. The basic ones are all well known, like prevention of osteoporosis, heart disease, and senile dementia. Even these benefits have been discounted and underplayed by purveyors of estrogen replacements that do NOT result in strong bones, decreased atherosclerosis and good cognition in the aging woman. 

There are other benefits that are less well known. Estradiol is partly responsible for catalyzing the brain cell repair induced by human growth hormone. It also co-stimulates serotonin, endorphin, and dopamine receptors in the brain to function as an antidepressant, decrease pain thresholds, and increase alertness and memory and libido. It also promotes healthy and sound sleep by interacting with melatonin in the midbrain and brainstem receptors. It strengthens connective tissues in the bladder and joints as well as having a DIRECT effect on the bladder lining and smooth muscle of the bladder and urethra. These are just a few of the effects of estradiol. 

The woman’s body is a machine designed to run efficiently using estrogens, but NOT JUST ANY ESTROGEN.  Receptors are very specific about what should bind to them and the human estrogen receptor requires human estrogen. Why not give back what is lacking…exactly what the body is asking for, or rather screaming for. I’ve seen doctors go to great lengths to avoid the use of human estrogen. They give lots of antidepressants, antihistamines, even vitamin E (which does reduce hot flashes and at the same time is a fine antioxidant) but none of these produce the same effects on the body as human estrogen. The woman does NOT have a Prozac deficiency and menopause is not an allergy requiring antihistamines, it is a HORMONE deficiency.

So let’s look at the hormones that are involved, now that we’ve established that they are safe at physiologic doses for 35-40 years and that we are going to replace them at lower levels still.

The human ovary makes several estrogens, but there are three that predominate, Estrone (E1), Estradiol (E2), and Estriol (E3). Estriol is the most abundant and accounts for 60-80% of the total estrogens. Estradiol and Estrone account for only about 10-20% each.

Here’s the Quick Guide:

 

Estriol:

  • Accounts for 60-80% of total circulating estrogens
  • Is made in huge amounts by the placenta during pregnancy
  • Has a weak effect on the uterus, strong effect on skin, hair and vaginal tissue
  • Probably accounts for the “glow” of pregnancy
  • Appears to “protect” the uterus and breast from the strong stimulus effects of estradiol and estrone by binding about 30% of the estrogen receptors in these tissues and may have its anticancer effect partly by this mechanism and partly by binding to a different subset of estrogen receptors than the other two estrogens
  • Swedish study showed that estriol alone improved urinary symptoms in 75% of women tested and vaginal dryness in 98% of these women.

 

Estradiol:

  • Accounts for only about 10-20% of circulating estrogens
  • Made in the ovary in highest amounts in mid-cycle (days9-10) at the time of ovulation as well as during pregnancy
  • Begins to decline often in a woman’s mid-thirties, or some 10 years pre-menopause
  • Stimulates serotonin, endorphin, and dopamine receptors in the brain thereby functioning as an antidepressant and increasing pain thresholds and libido
  • Promotes bone formation and muscle mass
  • Has a direct effect on maintaining the bladder lining and the smooth muscle of the bladder and urethra and connective tissues supporting the bladder
  • Increases HDL
  • Say it again: It increases sex drive and frequency and intensity of orgasms
  • Can decrease dramatically within 3-5 years post hysterectomy and a hysterectomy can result in a 3-4 year earlier menopause
  • Days 1-5 of cycle: (during menstruation) Estradiol levels fall
  • Days 6-14: Estradiol levels rise at ovulation
  • Days 15-28 Estradiol levels fall again to start the cycle over

 

Estrone:

  • Accounts for 10-20% of circulating estrogens
  • Thought to be a “storage form” of estrogen
  • Made in the ovary and liver and adrenals and in large amounts in the fatty tissue (so overweight women have much lower menopausal symptoms)
  • Promotes abdominal fat formation and the “apple” appearance of older women
  • High levels are associated with increased breast and uterine cancers. So keep body fat to a minimum both pre and post menopause otherwise the estrone levels will be elevated
  • Is in a 1 to 1 ratio with estradiol pre menopause, but a 2 to 1 ratio after menopause

 

Progesterone:

  • After ovulation, the corpus luteum, the leftover capsule remaining in the ovary after the egg pops out begins to make progesterone in very high amounts. This helps prepare the uterine lining for implantation of the egg if it is fertilized.  So highest levels occur from Day 15-24
  • Day 28 levels begin to decline back to low levels and the uterine lining then sloughs off in menstruation
  • Functions as a neurotransmitter both by itself in memory and mood, and also by promoting GABA production in the brain which is a “tranquilizing” neurotransmitter.
  • Produces a calming effect and can alleviate, if balanced with estradiol, PMS symptoms as well as the mood effects most women experience around and after menopause.
  • Maintains uterine lining
  • Protects against fibrocystic breasts
  • Promotes osteogenesis (bone formation)
  • Normalizes zinc and copper levels
  • Promotes thyroid function
  • Helps protect against endometrial (uterine) cancers
  • Increases sex drive

 

Testosterone: 

  • Made in the ovary and adrenals of women
  • Levels fall dramatically after menopause and hysterectomy (about 50% drop)

-which results in:

  • decreased sex drive
  • bone loss
  • muscle loss
  • depression
  • fatigue
  • myalgias (bone, joint and muscle aches and pains)

 

 

Premarin: 

  • Contains 75-80% estrone, 6-17% equilin (a horse estrogen), a small amount of estradiol 
  • identical to human estradiol and two other horse estrogens
  • Has several very potent breakdown products (metabolites) that continue to “drive” the estrogen receptors in the uterus and breasts. One of these 17-beta-dihydroequilin, is 8 times more potent than the parent premarin in inducing endometrial growth….this may account for the increased cancer risk observed with prempro in the women’s health initiative studies, though this is yet to be determined.

 

Perimenopause: 

  • Begins as much as 10 years prior to disappearance of cycles
  • More and more cycles fail to actually have an ovulation associated with them, though may still be menses.
  • Estrogens decline resulting in increasing depression, anxiety, irritability, and loss of libido
  • Weight gain as estrone begins to become the dominant estrogen
  • If no ovulation occurs, then no progesterone is secreted and this makes mood changes even worse and sex drive even less.

Still working on this page in my spare time. All women need a doctor that understands hormone balance and receptors and what can go wrong and how to fix it.