Pamela R. Yoder, MD, PhD

Losing your keys? Losing your patience? Losing your mind? If you are a midlife woman having difficulties, the solution may be increasing your estrogen level. More and more research studies are showing beneficial effects of hormone replacement

 on mental functioning. Women taking estrogen showed increased brain activation and reinstated patterns observed in younger subjects performing memory tasks, according to a recent study.

This study found altered neural circuitry in certain parts of the brains of postmenopausal women (average age 50) as they performed memory tasks. In a well-controlled experiment, 46 women were tested when they were taking estrogen and when they were taking a placebo with no estrogen. The dose of estrogen was what is typically prescribed to postmenopausal women (1.25 mg of conjugated equine estrogens).

I conducted a phone interview with Sally Shaywitz, M.D., of Yale University School of Medicine

. She was the lead author of "Effect of Estrogen on Brain Activation Patterns in Postmenopausal Women during Working Memory Tasks" published in the April 7, 1999, edition of the Journal of the American Medical Association [JAMA, 1999, 281(13), 1197-1202].

The authors included collaborators from pediatrics, neurology, diagnostic radiology, gynecology, and applied physics. This experiment used a unique means of studying mental processes-the functional magnetic resonance imaging (MRI). Dr. Shaywitz says, "Almost a decade ago, my husband and collaborator, Dr. Bennett Shaywitz first suggested that our research group use functional MRI to study reading and memory. It is a noninvasive test with future potential for being used clinically." She writes, "In performing a cognitive task, such as working memory, blood flow

 and oxygen concentration are altered in those brain regions engaged by the task" (p. 1198). In this study, the functional MRI found that while on estrogen compared to placebo women's brain activation patterns during memory tasks resembled those associated with younger (compared to older) people.

We talked about the implications of these findings for midlife women. Dr. Sally Shaywitz states, "I seem to have become the repository for women's stories of memory changes". Some women told her they noticed improved memory after starting estrogen replacement therapy. Others came forth with reports of forgetting simple things and of being too embarrassed or afraid to tell their doctors. "Many women feel that there is a prejudice against menopause," she explains.

Dr. Shaywitz points out, "Every woman who lives to the age of menopause will go through these changes [in mental function]." Patients should not be intimidated about talking openly with their healthcare providers

. Not all problems are due to sleep deprivation, depression, or aging alone. Physicians should inquire about cognitive changes in women in their late 30's or early 40's whose estrogen levels are beginning to decline. Dr. Shaywitz says, "Verbal memory, fluency, and articulation are functions used in everyday life that may be sensitive to estrogen".

This study opens the door to future research of mental functioning in midlife people. "Brain circuitry can be changed. Midlife is apparently a time of great brain plasticity. The brain can rewire!" Dr. Shaywitz exclaimed. The evidence is mounting that estrogen therapy CAN improve the daily life of many women. However, this is a complex issue and must be made on a highly individual basis. See your doctor about what you may be able to do to improve yours.

Articles

Losing your keys? Losing your patience? Losing your mind? If you are a midlife woman having difficulties, the solution may be increasing your estrogen level. More and more research studies are showing beneficial effects of hormone replacement on mental functioning. Women taking estrogen showed increased brain activation and reinstated patterns observed in younger subjects performing memory tasks, according to a recent study.

Staying Smart with Estrogen: Estrogen Replacement and Mental Functioning

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 "We're at the 43rd annual meeting of the       American Institute of Ultrasound in Medicine in San Antonio, Texas. Dr.       Steven Goldstein has agreed to speak with us about issues related to       imaging of a woman's uterus, ovaries, breasts, and the treatment and       avoidance of treatment by use of ultrasound imaging."
       
       

       "Ultrasound is a tremendous modality, and with the introduction of       transvaginal probes about a decade ago, the ability to image the ovary and       uterus in such close proximity, well, it's as if you're doing ultrasound       through a low-power microscope. We're seeing detail that you literally       could not see with your naked eye if you were looking at it, holding it in       your hand at arm's length, and squinting at it. This tremendous detail has       really revolutionized the application of ultrasound in the practice of       gynecology. One of the areas I think is most exciting, and that I've done       the most work in, is staying out of the operating room with women with       abnormal uterine bleeding, and it's specifically perimenopausal women,       mainly between thirty-five and menopause. You cannot go from having       regular ovulatory cycles every twenty-eight or thirty days to being       menopausal without going through a transition when you don't ovulate on a       regular basis. When you don't ovulate, you don't make progesterone, and       when you don't make progesterone if the estrogen level is relatively       constant, the endometrial lining will be stable, and women can go five,       six, or seven weeks without bleeding. Then they will usually present and       be evaluated, and often when they're not pregnant they're given medicine       to bring their period on for gestational agents. But the same physiology       of not ovulating, if the estrogen level fluctuates, will re-stabilize the       lining of the uterus and these women can bleed seventeen, twenty-one, or       fourteen days. When that happens two or three times in a row, over the       last sixty years in this country you got a D&C, hysteroscopy,       endometrial biopsy, or some sort of sampling because the gynecologists       always felt the need to exclude some form of pathology - polyps,       hyperplasia, pre-cancers, cancers, or fibroids. When none of that is       present, then they're left with the diagnosis of what we call, by       exclusion, 'hormone imbalance,' which is nothing but dysfunctional uterine       bleeding. So if we could reliably diagnose lack of significant pathology,       polyps, pre-cancers, or cancers non-invasively with ultrasound or some       fluid enhanced ultrasound - which is what we want to discuss - then many,       many women can avoid having any kind of endometrial sampling, D& C       procedures, and the like. The work that I presented today and that we have       been talking about now for quite some time suggests we can use ultrasound       to measure endometrial thickness. The concept that's important is that it       needs to be done just as the bleeding episode has ended, when the lining       of the uterus is going to be as thin as it's going to be all month long.       So if it's the last day or two of staining but the tissue has mostly       passed, or the first day, two, three, or four after the bleeding has       ended, a thin, distinct endometrial echo on ultrasound is uniformly       associated with lack of significant tissue. If for some reason you can't       see a good echo on ultrasound, or if it is not a thin echo, then we put       about 10 to 20 cc's, or a tablespoon, of sterile saline into the uterine       cavity while we're doing the sonogram. The way we put that in is through a       catheter that literally looks like a piece of spaghetti before you cook       it. It is an absolutely painless procedure and can be done by your       physician himself or herself at the time of a no-blood exam. If it shows       that there is no anatomic abnormality, then the bleeding can be treated       hormonally because the bleeding is, in fact, hormonal."
       
       

 "So a       woman can come in and have this study done rather than having an       endometrial biopsy?"
       
       

       "Absolutely. In fact, I had a nurse in day surgery recently say to       me, 'Dr. Goldstein, how come all your patients have something?' Makes you       a little paranoid at first, but I said, 'what do you mean?' She said, 'you       know, today you did two D&C's and both women had polyps, and last week       you're here and one woman had a polyp and one woman had a fibroid, but       they always have something. When the other doctors come, sometimes they       have something but a lot of times they don't.' I told the nurse, 'that's       because you never see the people who have nothing. We are able to diagnose       the lack of a polyp or a fibroid with ultrasound and some fluid upstairs       instead of coming to the operating room.'"
       
       

 "Now,       you're a general gynecologist, trained especially in ultrasound?"
       
       

 "I       am a full Professor of Obstetrics and Gynecology at NYU, and in my       clinical practice I practice all aspects of obstetrics and gynecology. My       academic interests have been in ultrasound in women. When vaginal probes       came out, I became more involved in gynecologic ultrasound, opposed to       obstetrical and the peri- and post-menopausal patient. Actually, when you       sit down and talk to peri-menopausal patients who have some of these       irregular bleeding abnormalities, you'll also find out that there is a       flood gate of psycho-social symptoms that seem to go along with that era       of time - mood swings, sleep disturbances, memory lapses, the inability to       concentrate, free-floating anxiety, the feeling that something's happening       here, not being on top of your game, etc. For many women this is long       before their first hot flash. My patients are pretty savvy, and by the       time they have hot flashes and a dry vagina, they know what's going on.       But sometimes these symptoms, which may be subtle or not so subtle in some       people, can manifest themselves up to a decade beforehand. I can't tell       you the number of patients who've gone to the doctor and said, 'could I be       beginning my changes?' Someone sends out a blood test on an estrogen level       that comes back in a pre-menopausal range, and they're told 'no, you're       not, this isn't hormonal. You're just stressed, your husband had an       affair, your youngest is going to college, or you didn't get the promotion       you deserve - try this Prozac.' When in reality, I believe that for a       significant number of women the fluctuation of levels of unopposed       estrogen in this transitional phase is the culprit for a significant       portion of how they feel. The treatment for this dysfunctional bleeding       and a lot of this irregularity, in my mind, is an ultra-low dose birth       control pills. They're designed specifically for women in their forties       who turn off their own ovarian estrogen production and instead substitute       a very low dose of estrogen and progesterone all month long, often giving       women back a sense of equilibrium and also solving the abnormal bleeding       problem."
       
       

 "So if a       woman comes to you in her early forties and is having problems with sleep,       irregular periods, light periods, or some mood or behavioral changes,       would you recommend that?"
       
       

 "In       women who are non-smokers, there is excellent reason for them to consider       a trial of low-dose birth control pills. I feel very confident about it,       and there's a lot of overlap. I mean, I have some of those symptoms, and I       don't make any estrogen. So clearly this is not all estrogen-related, but       I can tell you this: whatever portion of a particular patient component is       hormonal, you can take that off the table by suppressing her cycle. I've       stopped calling these birth control pills. I now refer to them as cycle       regulators, because you just can't take a forty-three year old woman who's       had her tubes tied and say 'I'm going to put you on birth control pills.'       It's not for contraception, it's for cycle regulation."
       
       

 "Some       people who have had hormonal treatment for augmentation or replacement       have noticed some changes in their breasts, for example."
       
       

       "That's a very interesting and astute point, and you use a good word,       which is augmentation. There are many physicians, obstetricians,       gynecologists, and family practice physicians who don't seem to understand       how to use hormones in the perimenopausal woman. Perimenopausal women are       making estrogen often in very fluctuating amounts, and in fact, some work       done recently showed that perimenopausal women may actually make more       estrogen in an atonic, unopposed fashion. At the very end, when you get       the hot flashes and dry vagina, there are low estrogen levels, but I       believe it's the fluctuation earlier in the perimenopause, so if you       simply give these women estrogen, it's just your fluctuation plus. And       I've seen some incredibly high levels of estrogen in women who were given       traditional estrogen supplements. The key to the low-dose birth control       pills is that they suppress ovarian function. It turns off your own       estrogen and substitutes a small regular amount all month long, which goes       together with people's fear of breast cancer. Let me be more specific.       Women are afraid of breast cancer and women believe, and it may be true,       that estrogen promotes breast cancer. I don't think it induces breast       cancer, but I think long-term estrogen probably does promote breast cancer       somewhat. So if you take a post-menopausal woman who is making virtually       no estrogen and you give her hormone replacement therapy, clearly, she's       going to have more estrogen to her breasts then if she does not take it.       That's easy for patients to understand, and that's why many patients are       fearful of hormone replacement therapies in spite of its benefits. The       perimenopausal woman to whom you offer birth control pills is reluctant to       take this because she thinks she's adding more hormones to her body, and       to her breasts. She often doesn't realize what I think needs to get       across, and this is that those pills, by suppressing her own ovarian       function, are now turning off what she makes and substituting 20       micrograms of ethinyl estradiol, which may in fact offer less risk to her       breasts in the long run than what she's already making on her own. Think       about it... There are really no good studies on what the equivalent dose       is, but if you look at the observational studies, women who took birth       control pills years ago in college ten or twenty-five years ago have no       increased risk of breast cancer. The pills those women took contained 50       and 80 micrograms of estrogen, and the pills we're using now are 20       micrograms. That's anywhere from one quarter to forty percent of the       estrogen that woman were on in the past, and those women who took the       pills in the past have no increase in breast cancer. Perhaps with this low       dose, in ten or fifteen years we'll find that these women actually had       less of a risk for breast cancer. There's good scientific evidence that       they have less ovarian cancer - eighty-five percent of ovarian tumors are       of the capsule of the ovary that bursts and repairs and bursts and repairs       with each ovulation. For every year you suppress ovulation, you take birth       control pills, and you have a ten-percent reduction in ovarian cancer. So       there are tremendous benefits to women who are non-smokers in their       forties for being on cycle suppression/cycle regulation. They never have       the mood cycles or psychological symptoms that we were describing caused       by the fluctuating hormones. Let's face it, some of them may be depressed,       and some men are depressed, but for a lot of women, a significant portion       of how they feel is related to fluctuating levels of estrogen. So if       you're on these pills, you don't have a cycle. It's now stable all month       long, so that's a benefit, and you're at less risk for ovarian cancer -       that's scientifically proven. In fact, the hypothesis here is that it may       be better for your breasts than the estrogen your own body makes."
       
       

 "If a       woman has had a hysterectomy, is she a candidate for estrogen alone, or       should she be taking a combination?"
       
       

       "That would depend on whether she has ovarian function. These are       different issues you're talking about here. If you've had a hysterectomy,       there's no longer any fear of endometrial cancer, so you don't need       progesterone to protect the endometrium. But if you've had a hysterectomy       - which simply involves removal of the uterus - and your ovaries are still       functioning, if they start to make fluctuating levels of unopposed       estrogen, you may not have the bleeding irregularity that brings women to       see me and try the saline effusion sonography that we were talking about.       The changes in moods, sleep patterns, and concentration that may be       hormonally mediated will still be present in a woman who has had a       hysterectomy, but her ovaries are maintained. So that woman should still       take low-dose birth control pills if her ovaries are functioning. If she's       had her ovaries removed, then I think she's an excellent candidate for       hormone replacement, which in her case doesn't need progesterone because       the only point of the progesterone is endometrial protection against       endometrial cancer."
       
       

 "There       are many mid-life women that are part of the sandwich generation and have       many, many hats to wear and no time for any additional causes of stress,       such as surgery, in their lives. Is there an opportunity to use the       ultrasound also to decrease their need for surgery if they develop an       ovarian cyst, for example?"
       
       

       "I've spent most of my academic career working on this. Ten or       fifteen years ago, if you were post-menopausal and you had an ovarian cyst       that was cancerous until proven otherwise, you had an operation and they       removed the uterus, tubes and ovaries. I actually published a third paper,       but it had been a six-year study and, in my mind, the largest and the       earliest in 1988, that suggested that simple cystic masses up to 5 cm were       rarely malignant and didn't necessarily need to be removed. I would say at       this point that's probably standard. If you have a smooth-wall, unilocular,       simple cystic structure of an ovary that looks by its appearance to be       absolutely benign, we would no longer do exploratory surgery and remove       it, and I'm glad that I made that happen. There may still be some places       where people remove it if the patient has a cancer phobia, but we know the       incidence of malignancy in that kind of appearance cystic structure is       virtually zero. If you start to look at women in general with an       ultrasound, you see that 10% to 17% of women in that age group will have       some form of simple cystic structure in the ovaries, but you're certainly       not going to operate on all these people, especially since the incidence       of malignancy is virtually zero. The same thing with fibroids - we could       discuss fibroids, and I can't tell you the number of women who have       hysterectomies because there are fibroids present. It's amazing how much       everybody wants to explain any symptoms they have in women with fibroids       on their fibroids. It often coexists. Fibroids have virtually no potential       of undergoing malignant transformation, so malignancy is not the issue. If       the bleeding is not a major problem and people are not anemic or troubled       by the pattern of bleeding and you can see the ovaries on ultrasound, we       used to think you had to take out the uterus because we couldn't feel the       ovaries. Now there's ultrasound, and if you know the ovaries are normal       then there's no reason to remove the uterus just because it gets to a       certain size and the ovaries are no longer palpated on an exam. If you       really want to extend the conversation, I think ultrasound should be part       of the overall gynecologic visit. Most of the information that we're       trying to establish with examining a patient at the time of her visit is       objective information to the gynecologist. Is this uterus normal-sized,       does it tip forward, does it tip backwards, is this a normal ovary, does       this ovary have a cystic mass on it? This is all objective information,       and if you have the equipment available and the know-how, you can get this       information in a matter of seconds. I have seen equipment that will be to       these ultrasound machines what the laptop is to the computer, today.       There's no doubt in my mind that in fifteen years students are going to       look at us and say, 'wait a minute, you used to feel without looking? How       did you know what they had?' Just like now, when I say to a student, 'you       know when I was a student, we use to listen to the baby's heart every       fifteen minutes in the first stage of labor, and every five minutes in the       second stage, and we didn't have monitors at all.' They look at me like,       'you didn't have a monitor!?' It's a similar kind of thing, but I think we       will be seeing something like the ultrasound stethoscope, and I've seen       prototypes of this. I think there will be some out by the ACOG meeting in       May, all these prototypes."
       
       

 "As a       woman and Director of Women's Services, I find all of this wonderful news,       and I thank you for your time."
       
       

OBGYN.net Conference CoverageFrom American Institute of Ultrasound in MedicineSan Antonio, Texas - March, 1999

Pamela R. Yoder, MD, PhD

Articles

Staying Smart with Estrogen: Estrogen Replacement and Mental Functioning

Ultrasound & Peri/Menopausal Women's health