Good morning! I am Dr. Becky Haak and today begins your forray into the world of Women’s Health. Before delving into the specifics of female reproduction and diseases of the reproductive tract, we’re going to take an hour to look at ways in which GENDER affects health and disease. Specifically through FORM, Function, and Foundations.
Female anatomy is different than male anatomy in many ways. Right now, we’re going to think about the difference in urethral length, urethral position and pelvic floor supports.
In a newborn baby the average length of the urethra is about 1 cm- the width of my finger. The length of a baby boy’s urethral is 3-4 cm, approximating the length of my finger.
Urethral length , the position of the urethral opening in relation to the rectum-these are specific anatomic differences, leading to more urinary tract infections in females with possible long term damage to kidneys. But what about other anatomic issues over the lifespan of a female?
With adolescence comes increased estrogen leading to thickening of the vaginal mucosa. The slide shows a healthy vaginal epithelium with the lots of blood vessels below the surface, a thick intermediate layer above the basalis, and lots of superficial cells filled with glycogen.
The reproductive organs hypertrophy and mature. The striated muscles and connective tissue in the pelvic floor support these organs as well as supporting the bladder and rectum.
During pregnancy, the growing baby and uterus exert ongoing and increasing pressure against the pelvic floor. With vaginal delivery there can be permanent damage to these supportive muscles, ligaments and the nerve supply.
Over the course of a lifetime, anything that increases abdominal pressure can further weaken this pelvic floor support mechanism. More babies, heavy lifting, pushing, pulling, carrying, physical labor and obesity all contribute to pelvic floor damage.
With menopause, estrogen levels decline and that thickening of the vaginal epithelium we saw with adolescence, reverses. On the right is the vaginal histology WITH estrogen as previously described. On the left, is vaginal epithelium without estrogen- only a few parabasal cells on top with much less blood flow, less collagen below, allowing much easier disruption.
When the pelvic supports are damaged and the elasticity wanes without estrogen, disorders of the pelvic floor occur. The top picture shows the uterus descending, coming down through those weakened supports. The lower pictures show dynamic MRI of a women bearing down and clearly shows the pelvic organs coming lower and lower as she strains. Every time your grandmother tries to move the couch or carrying the groceries , this may be happening, until ultimately the pelvic floor is so damaged, that the pelvic organs are falling out even without any pressure and she’ll describe feeling something coming out of the vaginal all of the time.
From birth to senecense, gender specific anatomy alters health and pathology.
Part II: The way our bodies function , our physiology, is also altered by gender.
In 1991, Dr. Bernadine Healy was appointed by President Bush to be director of the National Institutes of Health. She is a cardiologist and the first woman to direct this institution. Dr Healy initiated a large project called the Womans’ Health Initiative. WHI was a nation-wide project involving 161,000 women ages 50-79 over 15 years. It’s goal was to develop prevention strategies for breast cancer colon cancer, heart disease, and osteoporotic fractures in women.
The #1 cause of death for all women is cardiovascular disease, yet in 1991 when WHI began, heart research had been conducted almost exclusively on men. Since women experience their first MI about 10 years after their male counterparts, we assumed that ESTROGEN was protecting their hearts.
In 1996, American College of Obstetricians and Gynecologists developed this pamphlet for patients, touting the cardiovascular protective effects of estrogen. We, as gynecologists, were getting referrals to place women on estrogen to help protect their hearts.
While we were excited about the postive impact of estrogen on HDL, we’d sort of forgotten that there is a negative impact on clotting. Remember this clotting cascade? Production of a lot of these cofactors in the liver is increased by estrogen. It also appears to decrease production of Antithrombin III.
So when the blood under estrogen effect flows through a vessel distupted by plaque it is more likely to clot.
In 2004 this study came from the investigators of the Women’s health Initiative , stating quite clearly that estrogen and progesterone did NOT protect women against MI> There have multiple other studies verifying this.
So , how does gender impact cardiovascular function specfically myocardial disease? Only 50% of women have classical chest pain as their presenting symptom with an MI> on the average we’re 10 years older with our first MI but more likely to die of it than men and more likely to have congestive heart failure if we survive. In women , the cause of our MI will probably be Microvascular Disease – disease in the small arteries of the heart- not the big ones, subsequently, abnormalities are less likely to show up on conventional angiography and are less amenable to routine treatments such as stents and bypass grafts.
Estrogen and physiology – thanks in part to Dr Healy and the Women’s Health Initiative we’re more aware this is not just a reproductive issue.
Lastly- Where gender specifics impact health and diseased at our very foundations- the cell.
Hormones exert their action on specific target tissues through cellular receptors. The response to a hormone is specific to the receptor and the cell containing that receptor.
Let’s take a look at the Tamoxiphen story.
70-80% of breast cancers abnormally express hormone receptors on their cells. When bound these receptors cause abnormal proliferation of the cancer cells. Mid 1970’s tamoxiphen was developed. It is a molecule that sits nicely in the estrogen receptor on these breast cancer cells and does nothing. It modulates the estrogen receptor so to speak. Though this has been a great move forward in treating Estrogen-receptor + breast cancers, it was found to have a different effect in the uterus.
Though tamoxiphen BLOCKS estrogen receptors in the breast, it STIMULATES estrogen receptors in the uterine endometrium. Bummer. While stopping proliferation of breast cancer cells, it simulatanous has the unwanted effect of increasing uterine cancers. So the race was on to find molecules that altered estrogen receptors in various tissues to have the effect we desire for a specific disease.
In the late 1980’s Eli Lilly was working on one of these Selective estrogen receptor Modulators and found Raloxiphen, which didn’t have the effect on breast they were looking for but had a GREAT effect on estrogen receptors in BONE. When estrogen levels decline with menopause, the osteoclasts start outworking the osteoblasts, with resultant loss of bone density.
With a loss in bone density, fractures of the spine and hip become increasingly more common. In fact 1 out of every 2 women will experience an osteoporotic fracture at some point in their life. The ability to modulate estrogen receptors in bone has the potential for huge benefit to women, especially in light of our increasing life expectancy. In 1993 the FDA approved Raloxiphen for use in the prevention and treatment of osteoporosis.
Now we’re on a roll- SERM’s for the breast, for the bone; Anywhere else there might be receptors we can modulate to our benefit?
In the past decade, estrogen receptors have found in the eye, colon, and brain. Altered response to estrogen is seen in SLE altering disease progression. 2004-2005-2008-2010. This is where we are today; Just beginning to unravel the ways in which gender alters health and disease at the cellular level.
TO wrap it up, there are Gender specific anatomic differences in FORM which affect our susceptibiltiy to pathology.
Our hormones alter our physiology, impacting FUNCTION of both reproductive and non-reproductive organ systems.
And the final frontier: there are fundamental differences in cellular receptors and the hormones that manipulate them, which may provide opportunities to alter disease at the FOUNDATIONS- the cells themselves.
Thanks for your attention.
Introduction to women’s health/slides