Allison Taylor, MD, with the Center for Women's Health in Wichita, KS, presented about perimenopause and hormone therapy during a Women's Connection July 9, 2013, at Corporate Caterers. The event is sponsored by Via Christi Health.
Hello. My name is Dr. Allison Taylor. I am an obstetrician and gynecologist at the Center for Women’s Health here in Wichita. I am here this morning to discuss perimenopause. I have to admit that as I was preparing this talked, I found it somewhat difficult. I mean, I could stand here for hours discussing menopause. But perimenopause is a little different because it’s a much more nebulous subject. And I thought to myself – this subject is difficult for me to get my hands around and I do this for a living. So imagine how patients must feel. So my purpose today is to shed some light on menopause, its pathophysiology, its symptoms and most importantly – it’s treatment.
As an overview – this morning we will first review the definitions of menopause and perimenopause. Then we will very briefly review the physiology of the menstrual cycle
Menopause is defined as the permanent cessation of menstrual cycles. Once menopause has occurred, there is a decrease in the amounts of estrogen, progesterone and androgens produced by the ovaries. It typically occurs in the late 40’s to mid 50’s and the mean age of menopause is 51. Like pregnancy, although the symptoms can be distressing, I tell my patients all the time that menopause is a normal transition and a normal process, not a disease. And I Patients come into our office all of the time asking, “Am I menopausal yet?” And I answer that question with a question – are you still having periods? The diagnosis of menopause requires that you have not had periods for at least a year. So when patients say, yes, I’m having periods, but they’re only every 3 months or every 5 months. If that’s the case, then they are typically in perimenopause.
So what exactly is perimenopause? Technically, the term means “around menopause”, and that in itself is problematic. As we all know, when a car salesman tells you that a car is “around” $30,000, or your teenagers tell you they’ll be home “around” midnight, that is never good. Many women feel the same way about “around” menopause or perimenopause. Perimenopause is the time period during which the body makes its natural transition towards permanent infertility or menopause. During that time, estrogen, progesterone and androgen levels are fluctuating, but still present. Perimenopause typically occurs at some time during the 40’s, but for some it may occur as early as in their 30’s.
Like puberty (and we all remember how great that was!), perimenopause is a transition and not an event. It is a period during which ovarian function is declining but still present.
Before we discuss what’s going on in perimenopause, let’s briefly review what happens in a normal menstrual cycle.
The menstrual cycle is a very intricate and finely tuned machine that involves the interactions between what’s going on in the ovaries, what’s going on in the endometrium or uterus, what’s going on in the brain and what’s going on with sex hormones. All 4 of these cycles occur in tandem.
In the interest of time, we’re going to take a very simplified approach to looking at the menstrual cycle. There are several important players (both structures and hormones.) The hypothalamus is a specialized portion of the brain that links the nervous system or nerves to the endocrine system or glands. This occurs via the pituitary, which is another very specialized portion of the brain. Specifically, the pituitary gland makes lutenizing hormone and follicle stimulating hormone. These hormones send signals to the ovaries, which make estrogen, progesterone and androgens. And as we all know, estrogen, progesterone and androgen have numerous affects throughout the body.
FSH is released by the anterior pituitary. It tells the ovaries to develop a family or “cohort” of follicles (each of which contains immature ova). As the follicles grow, they release estrogen. One follicle becomes the dominant follicle, and the others die off. The dominant follicle is the one from which you ovulate on cycle day 14. It continues to produce estrogen. When the follicle has fully matured, it produces a spike in 17 OH progesterone, which inhibits the production of estrogen and this stimulates a release of LH from the pituitary (by decreasing the estrogen mediated negative feedback on GnRH in the hypothalamus.) The high levels of estrogen that occur with ovulation exert positive feedback on the pituitary to produce an increasing amount of lutenizing hormone (or an LH surge.) This LH surge is necessary for ovulation to occur. The rising LH causes the follicle to swell and rupture and ovulation occurs. If pregnancy occurs, estrogen and progesterone levels remain high and the fertilized egg is implanted. If pregnancy does not occur, the estrogen and progesterone levels fall and the endometrium sheds (or menses occurs.) The specifics of these interactions are not important. But the take home message should be that there are very intricate and specific interactions that occur between the brain, ovaries, and uterus during the menstrual ccle.
So again, we come back to this question – what exactly happens during perimenopause? But the reality is that there is not necessarily a singular answer. We are born with all of the eggs that we will ever have. They are just in an immature stage. Once we undergo puberty an start ovulating, every month one of those immature ova will mature and we ovulate. So as you can imagine, as we age, so do our eggs. And as we get closer to menopause, those eggs become less responsive to hormonal influences and it is more difficult for them to mature and develop properly. For this reason, during perimenopause, our fertility is decreased, there is an increased risk for birth defects, and menstrual cycles can become irregular.
During perimenopause, hormone levels are fluctuating, but periods (albeit possibly irregular) persist. And the reality is that estrogen levels are typically normal to elevated, but progesterone levels are often decreased. Recent studies have identified estrogen excess and progesterone deficiency as being a hallmark of perimenopause.
THE BALANCE OF PROGESTERONE TO ESTROGEN IS CRUCIAL TO THE FUNCTION OF THE FEMALE BODY. In a normally functioning female, that ratio after ovulation should be 20:1. Estrogen and progesterone affects many systems in the body. The symptoms of progesterone/estrogen imbalance are often misdiagnosed if a physician focuses on only a few symptoms in isolation
As many of you know, because of the myriad and varied symptoms of perimenopause, patients are often misdiagnosed.
Estrogen decreases your sensitivity to thyroid hormone. Progesterone allows the thyroid to function effectively. Progesterone/ estrogen imbalance affects the GABA receptors in the brain that affect mood and brain function. Aldosterone causes water retention. Progesterone decreases its effects when produced after ovulation. Without appropriate amounts of progesterone, aldosterone causes water retention. So the reality is that in many perimenopausal women, simply supplementing with progesterone will often help to alleviate symptoms.
Sex hormones are fat soluble. In order to become soluble in the blood, they are carried throughout the blood bound to proteins (sex hormone binding proteins.) 99% of them are bound. The functional hormones are those that are not bound to the proteins. It is often difficult to assess the amount of hormones affecting the tissues by evaluating the level of hormones in the blood.
ALLISON A. TAYLOR, M.D.
CENTER FOR WOMEN’S HEALTH
Physiology of the menstrual cycle
Pathophysiology of perimenopause
Symptoms of perimenopause
The permanent cessation of menstrual
Decrease in the amounts of estrogen,
progesterone, and androgens produced
by the ovaries
Mean age – 51
Natural process, not a disease
Technically means “around menopause”
Time period during which the body
makes its natural transition toward
permanent infertility (menopause)
Estrogen, progesterone and androgens
are fluctuating, but periods are still
Typically occurs sometime during 40’s
For some, it may occur as early as in their
A transition, not an event
ovarian function is declining but still
3 to 5 years before periods stop
PERIMENOPAUSE MAY LAST 2 TO 10
Sex hormone cycle
ALL OCCUR IN TANDEM
Links nervous system to
› Pituitary gland
Finite number of eggs
› Less responsive
Increased incidence of birth defects
› Often elevated
› Often decreased
› (largely because of the lack of ovulation)
THE RATIO OF PROGESTERONE TO
ESTROGEN IS ESSENTIAL TO NORMAL
FUNCTION OF THE FEMALE BODY
After ovulation, that ratio should be 20:1
Low estrogen is not necessarily the problem
Intermittently elevated FSH
Elevated, normal or depressed estraiol
deficiency same as
› Sleep disturbances
› Hot flashes
› Menstrual irregularities
› Breast tenderness
› Mood disturbances
› Decreased libido
› Weight gain
› Water retention
› Treats menstrual irregularties
› May make other symptoms worse
› Side effects
› Multiple breast biopsies
The “other” female hormone
Produced by the ovaries
Effects on various organs in the body
› Breast – decreases growth, promotes differentiation
› Bone – stimulates osteoblasts (lay new bone)
Estrogen inhibits osteoclasts
› Increases thyroid activity
› Stimulates normal sex drive
› Natural diuretic
› Decreases uterine muscle contractions
› Binds GABA receptors
Decrease anxiety and depression