Monthly Archives: October 2016

Antiaging effects of HRT

One of the obvious benefits of being on HRT in menopause is the anti-aging effect. It is very noticeable to my patients who are on hormones, that they look younger and better in comparison to their contemporaries not on hormones.

Climacteric. 2007 Aug;10(4):320-34.

A prospective, randomized, double-blind, placebo-controlled study on the influence of a hormone replacement therapy on skin aging in postmenopausal women.

Author information

  • 1Division of Special and Environmental Dermatology, Department of Dermatology, Medical University of Vienna, General Hospital, Vienna, Austria.

Abstract

BACKGROUND:

There is mounting evidence that menopause affects some functions of the skin. Hormone replacement therapy (HRT) appears to limit some of the climacteric aspects of cutaneous aging.

OBJECTIVE:

In the light of a growing interest in the endocrinological influence of skin, we performed a study evaluating the effects of HRT on skin aging in postmenopausal women.

METHODS:

Forty non-hysterectomized, postmenopausal women were included in this prospective, randomized, double-blind, placebo-controlled study on the influence of oral sequential treatment with a combination of 2 mg 17beta-estradiol/10 mg dydrogesterone (Femoston) for seven 28-day cycles. Skin elasticity, skin surface lipids, skin hydration and skin thickness were measured by non-invasive methods, and both adverse-event profile and clinical-dermatological status were evaluated.

RESULTS:

After 7 months of HRT, skin elasticity increased significantly at the right ramus of the mandible, while skin hydration tended to improve significantly at the right upper arm (inner side); skin thickness improved significantly but skin surface lipids did not. Absolute effects did not differ significantly between HRT and placebo patients. A dermatological evaluation was largely consistent with measurement results. Safety and tolerability of HRT were positive.

CONCLUSION:

The results showed improvements in the parameters involved in skin aging in the HRT group as compared to baseline. While skin aging is no indication for systemic hormone supplementation, a positive effect on aging skin can be observed.

Hormone-replacement therapy: current thinking.

Hormone-replacement therapy: current thinking. – PubMed – NCBI

Nat Rev Endocrinol. 2016 Oct 7. doi: 10.1038/nrendo.2016.164. [Epub ahead of print]

Hormone-replacement therapy: current thinking.

Author information

  • 1Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 622 West 168th Street, New York, New York 10032, USA.

Abstract

For several decades, the role of hormone-replacement therapy (HRT) has been debated. Early observational data on HRT showed many benefits, including a reduction in coronary heart disease (CHD) and mortality. More recently, randomized trials, including the Women’s Health Initiative (WHI), studying mostly women many years after the the onset of menopause, showed no such benefit and, indeed, an increased risk of CHD and breast cancer, which led to an abrupt decrease in the use of HRT. Subsequent reanalyzes of data from the WHI with age stratification, newer randomized and observational data and several meta-analyses now consistently show reductions in CHD and mortality when HRT is initiated soon after menopause. HRT also significantly decreases the incidence of various symptoms of menopause and the risk of osteoporotic fractures, and improves quality of life. In younger healthy women (aged 50-60 years), the risk-benefit balance is positive for using HRT, with risks considered rare. As no validated primary prevention strategies are available for younger women (<60 years of age), other than lifestyle management, some consideration might be given to HRT as a prevention strategy as treatment can reduce CHD and all-cause mortality. Although HRT should be primarily oestrogen-based, no particular HRT regimen can be advocated.

The timing hypothesis: do coronary risks of menopausal hormone therapy vary by age or time since menopause onset?

The evidence shows that oestrogen reduces the risk of heart disease (see earlier posts). However, women must start hormone therapy early in menopause to get this benefit. If it is left to late, hardening of the arteries will have already occurred and HRT will not undo this.

The timing hypothesis: do coronary risks of menopausal hormone therapy vary by age or time since menopause onset?☆☆☆☆☆

An invited review prepared for metabolism

Shari S. Bassuk1

,

JoAnn E. Manson2
Division of Preventive Medicine, Brigham and Women’s Hospital, 900 Commonwealth Avenue East, Boston, Massachusetts 02,215.
Abstract

The Women’s Health Initiative (WHI), a landmark randomized trial of menopausal hormone therapy (HT) for prevention of chronic disease in postmenopausal women aged 50–79, established that such therapy neither prevents coronary heart disease (CHD) nor yields a favorable balance of benefits and risks in such women as a whole. However, a nuanced look at the data from this trial, considered alongside other evidence, suggests that timing of HT initiation affects the relation between such therapy and coronary risk, as well as its overall benefit–risk balance. Estrogen may have a beneficial effect on the heart if started in early menopause, when a woman’s arteries are likely to be relatively healthy, but a harmful effect if started in late menopause, when those arteries are more likely to show signs of atherosclerotic disease. However, even if HT-associated relative risks are constant across age or time since menopause onset, the low absolute risk of CHD in younger or recently menopausal women translates into low attributable risks in this group. Thus, HT initiation for relief of moderate to severe vasomotor symptoms in early menopausal patients who have a favorable coronary profile remains a viable option.

What is the placebo effect and are doctors allowed to prescribe them?

What is the placebo effect and are doctors allowed to prescribe them?
February 23, 2016 3.04pm AEDT .

Author
David Neil
Lecturer, University of Wollongong

Disclosure statement

David Neil does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond the academic appointment above.
Partners

University of Wollongong

 

Suppose you discovered that some past prescription a GP gave you was actually a placebo. The treatment made you feel better, but now you know that the perceived benefit was really a placebo effect. Would you be upset at the deception, or pleased the doctor had found a way to help you?

There is little research on how often Australian doctors prescribe placebos. But, if they are at all like doctors in other countries, it is a common practice. Doctors break no law in using a placebo, but may cross an ethical boundary in choosing to deceive a patient, or to facilitate a patient’s self-deception.

What are placebos?

It’s important to distinguish between pure and impure placebos. A pure placebo is a straightforwardly fake treatment – a saline injection or a sugar pill, for instance, that is represented as a drug.

An impure placebo is a substance or treatment that does have clinical value, but not for the condition for which it is being prescribed.

Impure placebos can be vitamins, nutritional supplements, antibiotics for viral infections, sub-clinical doses of drugs, unproven complementary and alternative medicines, or unnecessary blood tests to calm an anxious patient.

A 2012 survey in the United Kingdom found 1% of GPs use pure placebos and 77% use impure placebos at least once a week.

Pure placebos involve an outright lie. Whether impure placebos should be characterised as deceptive is less obvious. With an impure placebo, the patient knows what he or she is actually taking, but may not realise the doctor does not expect the treatment to work.

The placebo effect is unquestionably real but not yet fully understood. It is now believed there are different types of placebo effect involving different mechanisms. These include response conditioning based on prior experience, expectation and reward effects mediated through the dopamine system and natural analgesia through the production of endorphins, the body’s own painkillers.

What triggers the placebo effect, though, is belief: the belief that you are receiving a treatment and that it will be effective. The placebo itself is simply a prop to sustain the illusion. Studies suggest coloured pills are more effective than white pills, two pills are more effective than one, injections are more effective than pills, placebos administered in hospital are more effective, treatments perceived to be expensive are more effective than cheaper ones and brand-name drugs are more effective than generics.

The placebo effect has an evil twin, the nocebo effect, where a patient experiences adverse side effects from a harmless placebo, or where the expectation of negative symptoms precipitates those symptoms. The placebo effect is ubiquitous, which is why placebo-controlled trials are important in drug evaluation.

A drug’s effectiveness is measured in terms of the extent to which it is better than a placebo. Not all of the benefits of drugs derive from the pharmaceutical compound itself. For many drugs, some part of the benefit depends on the patient’s beliefs.

Are placebos ethical?

The placebo phenomenon raises some difficult questions about truth and consent in medicine. The two primary ethical duties of doctors are to act in the patient’s best interests and to respect the patient’s autonomy.

The doctrine of informed consent dictates that patients have an absolute right to make treatment decisions based on full information about the risks and benefits of proposed treatments.

Yet the placebo effect suggests that complete information and unvarnished honesty are not always in the patient’s best interests. Sometimes it may be beneficial for patients to have expectations their doctors do not share.

Similarly, there is an emerging concern in the literature that telling patients about all the possible side effects of a treatment can trigger a nocebo effect, causing some patients to experience adverse side effects.

It is obviously important to know about the side effects of treatments, both for deciding whether to take a drug and to be alert to possible problems. But this kind of information is not therapeutically neutral. It can condition expectations or focus anxieties in harmful ways.

A cognitive intervention that can produce significant pain relief and measurable improvement for a variety of other symptoms is, unquestionably, medically important. It’s questionable, however, whether we should incorporate such an intervention into standard practice, given it requires deception.

Essentially, the issue is the placebo effect has a serious image problem. Discovering that an apparently helpful medicine was merely a placebo can be embarrassing, even shameful. It is often seen as implying gullibility or delusion, or perhaps that the illness was exaggerated.

The emphasis on deception frames the placebo effect as a kind of illusion that is “all in the mind”. But the placebo effect is not a weird anomaly. It shows us something about how the body’s responses to injury and disease function.

If beliefs, expectations and dispositions are involved in the neuro-physical mechanisms governing pain response, then it may matter a great deal how we understand, imagine and anticipate our own pain.

Meet the Super Flasher: Some Menopausal Women Suffer Years of Hot Flashes

Meet the Super Flasher: Some Menopausal Women Suffer Years of Hot Flashes

By Tara Parker-Pope
July 25, 2016 1:08 pm July 25, 2016 1:08 pm 409

– The New York Times <!–

 

Photo

Credit Kim Murton
What kind of hot flasher are you?

The hot flash — that sudden feeling of warmth that can leave a woman flushed and drenched in sweat — has long been considered the defining symptom of menopause. But new research shows that the timing and duration of hot flashes can vary significantly from woman to woman, and that women appear to fall evenly into four hot-flash categories.

Some women, called “early onset” hot flashers, begin to experience hot flashes long before menopause. Symptoms can begin five to 10 years before a woman’s last period, but the symptoms stop around the time of the final menstrual cycle.

Then there are women who don’t experience their first hot flash until after their final menstrual period, the “late onset” hot flasher. And some women fall into a group the researchers called the “lucky few.” Some of these women never experience a single hot flash, whereas others briefly suffer only a few flashes near the end of the menopausal transition.

And then there are the “super flashers.” This unlucky group includes one in four midlife women. The super flasher begins to experience hot flashes relatively early in life, similar to the early onset group. But her symptoms continue well past menopause, like those in the late onset group. Her symptoms can last 15 years or more.

The findings come from the Study of Women’s Health Across the Nation, or SWAN, a 22-year-old study that has been tracking the physical, biological and psychological health of 3,302 women from a variety of racial and ethnic backgrounds. The study is being conducted at seven research centers around the country and is paid for by the National Institutes of Health.

“It explodes our typical myth around hot flashes, that they just last for a few years and everyone follows the same pattern,” said Rebecca Thurston, senior author and a psychiatry professor and epidemiologist at the University of Pittsburgh. “We may be able to better help women once we know in what category they are more likely to fall.”

That includes women like Lynn Moran, a 70-year-old retired financial assistant who lives near Pittsburgh and falls into the “super flasher” category. She remembers having her first hot flash around the age of 47. While the symptoms were subtle at first, the hot flashes became more bothersome. “It was enough to wake me up out of a sound sleep,” she said. “I wasn’t sleeping well because they were coming all night long and during the day. I was miserable.”

Ms. Moran began hormone therapy, which helped but did not eliminate the symptoms. But when medical studies began to show health risks associated with the treatment, her doctor advised her to stop using hormones. She waited another 18 months until she retired, then stopped taking hormones in 2005.

The hot flashes “came back with a vengeance” and haven’t stopped since.

“I still have them. I still laugh about them,” she said, noting that she may experience several hot flashes a day. “I’ll be trying to get ready to go somewhere, curling my hair and have to redo everything and dry my hair again because I’ll be drenched. My makeup will literally run down my face. Here I am, 70 years old, complaining of hot flashes.”

Dr. Thurston notes that understanding variations on hot flashes is important to understanding women’s health in midlife. Several studies suggest that the timing and duration of hot flashes may be an indicator of a woman’s cardiovascular health. A 2012 study, published in the journal Obstetrics and Gynecology, found that frequent hot flashes were associated with higher cholesterol markers, particularly in thin women.

The latest findings from the SWAN study identified some patterns around the four subsets of women who experienced varying degrees of hot flashes. Women were distributed about equally among the groups, meaning 75 percent of women experienced some degree of hot flashes, while only 25 percent escaped the symptom.

Women in the early onset group were more likely to be white and obese. Women in the late onset group tended to be smokers. The lucky few women who had no hot flashes or only a few were more often Asian women and women in better health. The super flashers were more likely to be African-American. Women who were super flashers were likely to be in poorer health or to regularly consume alcohol. But the researchers cautioned that while they identified some statistical trends in each group, it’s important to note that each subset of hot flashers included a variety of women representing all races, ethnicities, body weights and health categories. No one factor appeared to determine a woman’s risk for any hot flash category.

For instance, while African-American women were three times as likely to be in the super flashers group, they represented only 40 percent of that group. The remaining 60 percent were white women, some Asian women and other groups.

Dr. Thurston said it is important that doctors understand that 75 percent of women have hot flashes in midlife and that for half of them — the late onset flashers and the super flashers — the symptoms persist well past menopause.

“It flies in the face of the traditional wisdom that women have these symptoms for three to five years around the final menstrual period,” she said. “We now know for most women that is patently wrong.”

In Conversation with Barry Marshall: using pathogens to help humans

In Conversation with Barry Marshall: using pathogens to help humans

March 30, 2016 12.11pm AEDT

Nobel Laureate Barry Marshall talks to Eijkman Institute for Molecular Biology deputy director of translational research David Handojo Muljono in Indonesia. Supplied

Marshall was in Indonesia on March 14 to 16. After giving a lecture at the Eijkman Institute for Molecular Biology in Jakarta, he spoke to Professor David Handojo Muljono, Eijkman’s deputy director for translational research who, like Marshall, is a clinician as well as a scientist.


David: Your discovery of H. pylori as the cause of gastric ulcer was a great contribution to the world. But it did not stop there: you have utilised a pathogen that “gives problems” to humans as a tool to help humans. How did the vaccine development begin?

Barry: The idea of delivering a vaccine with a bacterial vector [the use of bacteria as a vehicle for an element (gene or fragment of interest) of a microorganism by inserting it into the bacteria to induce immunity] has been around for 30 years. The beautiful thing about those vaccines is that you just take them in a drink and it gives you some protection by giving you a very mild infection and generating an antibody response.

But it may not be very effective the second time you have it because your body will quickly eradicate the vaccine strain.

When I looked at some of the data on the AIDS vaccination trials on HIV, it seemed to me the problem was that patients needed lots of boosters. If they have three of four or five or six boosters, maybe they would have enough immunity response to battle the HIV or to protect them from the HIV. But it’s not practical to give so many vaccinations.

At that point we were looking at Helicobacter and thought, well hang on a minute, Helicobacter infects you all your life and most people with Helicobacter don’t have the symptoms. In fact, at any point in time 80% of people feel fine.

We thought if you could put and find a harmless Helicobacter and clone in the HIV vaccine, or whatever vaccine you wanted really, you could give it to somebody and they would have a harmless Helicobacter infection and over many months the antigen will continue to be presented and it will be like having a booster every day.

It seemed a good idea to try. But we found some of our vaccine strains still were a little bit harmful. So we did not find a totally harmless Helicobacter.

However, I think the door is still open for us to use that strategy in specific diseases and specific antigens.

David: And other diseases such as hepatitis might be possible…

Barry: It’s still a unique idea with possibilities.

There is a good story related to this. When one of our patients developed an ulcer, it convinced us we needed to look at our data more carefully. We noticed in one of our experiments, looking at the immune system, we had a control group which had killed Helicobacter.

And we notice there’s an immune suppression in the killed Helicobacter almost as strong as immune suppression we sometimes see with live Helicobacter.

So, if Helicobacter activates T-regulatory cells and creates some immune suppression and switches the emphasis of the immune system in that way, well the killed Helicobacter seems to have an effect and would be 100% safe without the live [Helicobacter] problem.

So we switched over to that because there was a paper in New York which showed children with Helicobacter have reduced risk of any allergic disease.

And so, at least in mouse models, you can suppress the allergic response in mice with Helicobacter products. Live Helicobacter is the strongest but a little bit dangerous. But killed Helicobacter, we think, are 100% safe and still have a mild suppression to the immune response to allergens in the mouse models.

Now we’re creating a product that’s really an extracted product of H. pylori. We have to kill the H. pylori but the immune system still thinks it’s alive.

In Western countries, food allergies and different kinds of allergies are becoming more and more common in children. We think this kind of product in the first year of life, from six to 12 months for maybe three months’ time, given as a food additive or something like an oral medication that children might take easily, might switch the immune system back to the more “stone age” natural one, instead of the child being exposed to all kinds of infections.

David: And what about the vaccine?

Barry: The vaccine, we still have it up our sleeve and it’s going to be useful in special severe cases in different diseases, because certainly the live Helicobacter will be the strongest. But the killed Helicobacter is 100% safe.

David: How has industry responded to these innovations?

Barry: At the moment, it’s going to stay in academic research. The problem with Helicobacter, you probably have one infection in your life and so that means if you have the vaccine, you only need it once.

For a pharmaceutical company a flu vaccine is good because you give it each year. But a vaccine that you only use once in your life that’s not the sort of drug that drug companies get very excited about.

But countries and the World Health Organisation might be interested in that kind of thing. [It’s] still a great research project in principle.