The article is based on data from the “Study of Women’s Health Across the Nation” which followed 1,970 women between the ages of 42 and 52 for up to 10 years. During this period, the presence and/or absence of depressive symptoms was assessed by trained interviewers with a 20-item depressive symptom scale on a yearly basis. The women’s anxiety was assessed with 4 questions (and no, they had nothing to do with those of the Passover Hagadah) asking about the number of days in the two weeks prior to their visit that the woman had “irritability or grouchiness”, were “feeling tense or nervous”, felt  “heart pounding or racing” or “felt fearful with no reason”. The researchers then assessed whether the women had had a hysterectomy and if so, with or without an oophorectomy. Now, if you want to know the exact numbers while anticipating the results (hopefully, with no great nervousness or pounding heart), here they are:

A total of 1,793 women reached natural menopause, 76 had had a hysterectomy with ovarian conservation and 101 women had a hysterectomy and bilateral oophorectomy.  The participants were followed for up to 10 years after baseline. (There was an interesting disclaimer that was put in the study whilst describing results…for an unknown reason the women at the New Jersey site, all 131, were not included in the final results due to “reasons unrelated to scientific integrity”. As a former New Jersey-ite I had to wonder why?)

The researchers found that depressive symptoms declined before the final menstrual period or surgery and continued to decline after both. Moreover, regardless of whether the ovaries were conserved or removed, hysterectomy status has no effect on depressive symptoms initially or later. And anxiety scores did not change significantly in the years leading up to the final menstrual period or surgery, but they decreased during the period after the onset of menopause or surgery. Once more, regardless of whether the ovaries were conserved, hysterectomy had no effect on anxiety symptoms at the first annual visit or in the years that followed.

Now, for the caveats; which in this study are huge.  Firstly, the study was limited to women in mid-life close to the onset on natural menopause. We know that there can be significant health and mental risks subsequent to oophorectomy in younger women who have not already begun to experience the hormonal changes of menopause. In general early surgical menopause has been associated with significant mood changes, bone loss, possibly increased risk of heart disease and early onset of Alzheimer’s.) Secondly, and this is a big one… The authors stated that the “use of hormone therapy was associated with lower levels of anxiety and depressive symptoms. Hormones were used at some point by the majority of participants and, as expected, were particularly common among women with a hysterectomy.” but when they excluded the women who after menopause or hysterectomy with oophorectomy did not use hormone therapy, the trajectory of depressive or anxiety symptoms was not changed. Their final conclusion was that lasting effects on both anxiety and depressive symptoms do not need to be a major consideration for deciding whether to keep the ovaries during a hysterectomy.

I realize this was a somewhat confusing article with lots of facts that are first stated and then discussed with a scientific “there were exceptions and additional factors”. I, too, sometimes wonder why certain studies are published. Does this one mean that we should take hormones to preclude mood symptoms during or subsequent to menopause, after a mid-life hysterectomy or removal of the ovaries or not? As usual the answer has to be geared to the individual woman and requires consultations with her physician. But what I think it does say is that no matter what we do, once we go through the menopause transition, whatever mood changes we experience at that time, won’t get worse in the years to come.

We are reminded that Hippocrates used leaves from the willow plant to treat headaches and muscle pains; that in the 1800’s the active ingredient of aspirin was isolated, and that quinine from the bark of a cinchona tree was used to treat malaria as early as the 1600’s. Another malaria drug that contains an herb called Artemisia was used by Chinese healers for thousands of years. Clearly these herbs, plants and practices have been important in the development of healing and soothing medications.

The author, however, focuses on some of the expensive studies by the NCCAM that showed failure of efficacy. Apparently $374,000 was spent in an attempt to see if inhaling lemon and lavender scents would promote wound healing (it didn’t), $750,000 to establish whether prayer cures AIDS or hastens recovery from breast reconstruction surgery, $700,000 to investigate whether magnets would treat arthritis, carpal tunnel syndrome or migraine headaches (not proven), and $400,000 to find out if coffee enemas cure pancreatic cancer. (What do you think?) They have also investigated acupuncture and therapeutic touch and, so far, their controlled studies have found that they work no better than placebo. Ah, but “here’s the rub”… Placebos have often been found to alleviate many symptoms and make us feel better. They may “tell” the brain that something is being done and perhaps induce the release of neuromediators that block pain and promote symptom relief.

The author goes on to point out that there are scientists who are avid proponents of the value of negative studies. For example, studies have shown that combination measles-mumps-rubella vaccine does NOT cause autism. But he argues that a negative finding frequently does not change public behavior. There are still many parents who are afraid to vaccinate their children and as a result the rate of pediatric morbidity and mortality from these and other diseases has risen.

When it comes to megavitamins and supplements, there is an ongoing “Why not use it, it won’t hurt” attitude. He points out that several NCCAM-funded studies have shown that garlic does not lower low density lipoprotein cholesterol, ginkgo does not improve memory (I forgot about that one!), St. John’s wort does not treat depression, echinacea and megavitamins do not treat colds. And some studies have shown that megavitamins increase the risk of cancer and heart disease. Vitamins and supplements are not regulated by the FDA.  But these negative data do not seem to negatively impact our need to hope that they work. In 2010, the vitamin and supplement industry grossed $28 billion, up from 4.4% the year before. (I am thinking of having a vitamin of some sort named after me, it might provide a great financial legacy for my kids…just kidding!)

I want to quote the conclusion of the article, it was quite amazing: “Because negative studies performed without a sound biological basis have little or no success, it would make sense for the NCCAM to either refrain from funding therapies that border on mysticism such as distance healing, purging, and prayer; redefine it’s mission to include a better understanding of the physiology of the placebo response; or shift it’s resources to other NIH institutes

I think he makes a good point.

The April issue of the journal Obstetrics and Gynecology included an evaluation of proper use of an over-the counter single tablet emergency contraceptive called Plan B One-Step which was given to females aged 11-17 who requested emergency contraception at reproductive clinics. (I have to say that even I was appalled that 11 and 12 year olds were sexually active….but the authors pointed out that in actuality no 11- or 12 year olds were enrolled in the study, although statistics tell us that approximately 3% of teens initiate sexual activity before age 13.) The authors simply wanted to see if very young women would and could read the instructions and use the pill appropriately without interacting with providers.

A total of 345 females were enrolled in 5 cities, 279 were younger than 17.  This product was then given to participants who were eligible. They were then contacted 1,4, and 8 weeks later to assess use, pregnancy and adverse events.

As many of you know, the Plan B One-Step (one tablet of 1.5 mg levonorgestrel, a type of progestin that is in many birth control pills) has been granted approval by the FDA to be marketed as emergency contraception without a prescription for females aged 17 and older. It is restricted and can be given by prescription only for females aged 16 and younger. (And this decision created a huge political and gender based battle.) But despite the recommendations by major medical associations, physicians and women’s groups, the FDA insisted that additional data was needed demonstrating that females aged 17 and younger understood the “key concepts needed for safe and effective use for this product to be sold over-the-counter.”

This study pretty much answers this concern.  The participants had to agree and use the emergency contraceptive only after reading the information on the front and back panels without any assistance from the study staff or health care providers, as well as understand when and how to take it and the possible consequences. Parental consent was waived because minors can receive contraceptive services without parental consent in the states where the study was conducted. The study participants were considered appropriate (and understood that they were) if they responded yes to one of 4 questions that they were asked and they don’t want to get pregnant: Did they have sex but didn’t use a condom?  Did the condom break? Did they not use their birth control pills correctly? Did they have sex without any form of birth control?  And they were not eligible for the study if they thought they were pregnant or indeed were, they had unprotected sex more than 3 days before they requested the EC or they simply wanted to use EC every time instead of birth control.

Among the 298 participants who used this single pill, 274 (92.9%) used it correctly as labeled.  Selection and correct use was not associated with age. Fifty-seven participants (18.8%) used additional emergency contraception over the study period. (So repeat use was not common). Only seven (2.3%) who used Plan B One-Step became pregnant and there were no unusual adverse events.  The conclusions in the article were a sort of “see we told you so” to the FDA. “Restricting young females’ use of a single tablet emergency contraceptive by prescription only is not warranted, because females younger than 17 years can use it in a manner consistent with over-the-counter access.” I couldn’t have said it better myself!

A study attempting to answer this query was published in the April 4 issue of JAMA. Between April 2004 and February 2006, 2809 women at 21 sites through out the US who had an elevated cancer risk and/or dense breasts underwent a series of 3 annual screens with mammogram and ultrasound. Each test was independently given and the radiologists were blinded to the result of the prior test. After 3 rounds of both, 612 of the women consented to also undergo breast MRI. (Not everyone wanted it…breast MRI requires intravenous dye and can be a lengthy, uncomfortable exam.)

The median age of the women was 55 with a range of 25 to 91 years. Approximately 29% of the women were younger than 50 and 23% were premenopausal. Nearly 54% had a personal history of previous breast cancer. High risk women were defined as having one or more of the following: a known mutation for BRCA1 and BRCA 2, a history of prior chest radiation, a significant family history of breast cancer, a lifetime risk of over 25 % of developing breast cancer, a previous biopsy that showed atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ or any atypical growth that increased risk for future cancer. And finally the study included women who had demonstrated in previous mammograms an increased density in more than 25% of their breasts. (When the breast tissue is very dense, meaning the glands are not separated by fatty tissue, the mammographic image looks white, it’s hard to see white on white…and it’s the white distortions and calcifications that allow the mammographer to suspect and diagnose cancer. Moreover, dense breast are more likely to develop a malignancy.)

A total of 110 participants were diagnosed with breast cancer during the 3-year study. Thirty three (30%) were detected by mammography alone; 32 (29%) by ultrasound alone; and 9 (8%) by MRI after both mammography and ultrasound failed to detect cancer. Eleven cancers (10%) were not detected by any imaging. (The patient or physician probably found “something” during physical exam of the breast.)

What does this data mean? The researchers summarized the study by stating that supplemental ultrasound can increase cancer detection with each annual screen done in conjunction with mammography. They calculated that ultrasound adds detection of 5.3 cancers per 1000 women in the first year; 3.7 per 1000 women the second and third years, and an average of 4.3 per 1000 for each of the 3 rounds of annual screening for women who were at risk. The addition of MRI screening further increased cancer detection with a yield of 14.7 per 1000 women vs. mammogram plus ultrasound. Another way of putting it (for cost -effective reasons that are so important to the practice of medicine today): the number of screens needed to detect 1 cancer in high risk women was 127 for mammogram, 234 for supplemental ultrasound and 68 for supplemental MRI (after negative mammography plus ultrasound screening results).

They went on to state “one of the major concerns (aside from the cost, especially that of MRI) is the harm of extra testing and biopsies for women who don’t have cancer. Five percent of biopsies were prompted in the women screened with additional ultrasound. Obviously not all of them showed cancer. (This becomes a philosophical issue….. will high risk women take the chance of having an unnecessary biopsy on what turns out to be a false positive finding when there is also an increased chance of detecting cancer and treating it? )

In conclusion, the authors state that “for high -risk women unable to undergo MRI and for intermediate -risk women with dense breasts, including those with a personal history of breast cancer, this study supports the use of ultrasound in addition to mammography.”

Bottom line: Most women who are high risk for breast cancer due to a previous cancer, a strong family history of breast cancer or previous abnormal biopsies are aware of their risk and seek appropriate screening. (Or at least their physicians should.) But if you have no known risks for breast cancer, make sure you ask your doctor if your mammogram was difficult to read and/or displayed significant density. If so, you could benefit from additional ultrasound imaging. Now if only all of the insurance companies agreed… Perhaps this study will help get them to pay!

The Study of Women’s Health Across the Nation examined that question and found that, unfortunately the answer was “to some degree, yes.” This study, published in the journal Obstetrics and Gynecology in April, 2012, followed 3,201 women aged 42-52 years for 8 years. They were interviewed once a year and asked to recall the frequency and severity of hot flashes and night sweats during the previous 2 weeks. The women also underwent a physical exam and blood tests were done to check their lipids. The latter included low-density lipoprotein (LDL), high-density lipoprotein (HDL), Apolipoprotein A-1, apolipoprotein B, lipoprotein (a),  and triglycerides.  Blood estrogen (estradiol) levels and follicle stimulation hormone (FSH) were also checked to see if they had become menopausal. (Estrogen levels plummet and FSH goes up in menopause.)  Remember, all of the lipids (think fats in the blood stream) with the exception of the “good lipid” HDL encourage plaque development in blood vessels and subsequent coronary heart disease and stroke.

The average age of the women at the onset of the study was 46.  One third of the women had hot flashes; these increased over the years (as they transitioned into menopause) and at the 7th visit, 54% had significant hot flashes and 38% had night sweats. The factors that were associated with a worsening lipid profile at baseline included older age, Hispanic race, smoking, low education, not drinking alcohol, being perimenopausal at a young age, obesity, low physical activity, low estrogen level, high FSH and high anxious or depressive symptoms. But even when they controlled for all these factors which were present at the onset of the study, hot flashes and night sweats, particularly when experienced frequently were associated with higher levels of the lipids over the 8 year study period,  most particularly in leaner women. These lipid markers are well known to be associated with elevated cardiovascular risk.

I know it seems weird that the changes in the lipids were more common in thin women with hot flashes rather than obese women who experienced this symptom. The authors hypothesized that the effect of weight and BMI on lipids or vasomotor symptoms may have overwhelmed the more modest associations seen in the study.

What does this mean for women going through a difficult menopausal transition and why the correlation with cardiovascular disease? No one is sure.

This study simply raises concerns: if you experience significant hot flashes and night sweats during the menopause transition, make sure your physician checks your lipid levels. If they are elevated, they may portend the development of cardiovascular problems.  You and your doctor should consider appropriate prevention and if necessary, treatment

NAMS states that the decision to prescribe hormone therapy (HT) should be made based on a woman’s health, her symptoms, her preferences for quality of life as well as her personal risk factors. (Well, that has certainly not changed from what most of us told our patients in the past.)

They go on to state that once started, continuation is dependent on whether estrogen only or estrogen and a progestin are given. And severity of symptoms should be considered in any decision to terminate hormone therapy. In general they feel it’s “safe” ( the multiple authors use the term “a more favorable benefit-risk profile”) if estrogen therapy without a progestin (ET) is given for 7 years (and perhaps longer depending on the studies cited). But remember we can give estrogen without a progestin only if a woman has had a hysterectomy. If she has not had surgery with removal of her uterus a progestin should be given to prevent endometrial (uterine lining) cancer. In this later instance (i.e. no previous hysterectomy) duration of use of HT (estrogen plus a progestin) should probably be more limited due to the increased risk of breast cancer after 3 to 5 years.

The NAMS statement concluded the estrogen therapy is the most effective treatment of symptoms of vulvae and vaginal atrophy. They advise low-dose, vaginal local estrogen when the only symptom is vaginal atrophy (think dryness and pain with intercourse)…and then state that when this is the only form of estrogen used, there is no need for concomitant progestin.

Women with premature or early menopause who have no contraindications (clots, breast or endometrial cancer) can, and probably should, use HT at least until the median age of natural menopause (age 51). After that time, the same decisions should be made as for women going through natural menopause.

No increase in breast cancer risk was observed in the Women’s Health Initiative with use of estrogen in breast cancer survivors but… they pointed out that there is a lack of good data and one randomized control study found an increase in breast cancer recurrences. So they don’t recommend its use.

Finally they stated that both transdermal estrogen ( patches, creams and sprays) and low dose oral estrogen have been associated with lower risks of deep vein clots and stroke than that found with standard doses or oral estrogen, But they wouldn’t take the final step and commit to this, proclaiming that sufficient randomized studies to endorse this have not as yet been completed.

And finally the NAMS position ends with the statement that there is a “growing body of evidence that HT formulation, route of administration , and timing of therapy produce different results” In other words one size and one type does not fit all.

Starting hormone therapy, the type, route of administration, dose and duration of use remain important issues that all women going through menopause should discuss with their physicians. We now have more studies and guidelines to help you with these hormonal decisions.

Menopause is defined as a permanent cessation of periods for 12 months. And if wis use this 12 month definition, the only way to date menopause is to do so retrospectively. Before our ovaries run out of the follicles that produce the estrogen and progesterone needed to instigate our periods, they “sputter”. The follicles that have not been used up during our teens through our mid forties are the rejects and they simply do not put out (hormonally) as they should. This period of approaching follicular extinction is termed the menopausal transition. On average it begins at age 47 and lasts 4 years. During this transition, even though periods may come and go, symptoms such as hot flashes, sleep disturbances, vaginal dryness and pain with intercourse can occur.

There are more than 3000 chemicals inhaled in cigarette smoke. Many of them are detrimental to the health and well being of the follicles and can contribute to their early demise. The concerns about early menopause do not solely relate to symptoms. Early menopause increases the risk of cardiovascular disease, venus thrombosis (clots) and osteoporosis. Overall it increases the risk of mortality by approximately 2% per year. And to add insult to smoke injury, the combination of earlier loss of estrogen and current smoking further increases a woman’s risk of cardiovascular disease and death!

For this and so many other reasons, quitting smoking is the best thing a smoker can do for her health. Now would putting a picture of ovaries with a big red X over them help to convince women to stop smoking? I’m not sure … But it can’t hurt to add this to all the other warnings.