Melatonin is on prescription in Australia, not like the USA, where it can be bought over the counter. Some health food shops sell homeopathic Melatonin – the dose is so small it is unlikely to be of much benefit.

Does this supplement live up to its hype?

Alistair Gardiner|April 21, 2021

If you’ve been wandering the vitamin and supplement aisle of your local grocery store recently, you may have noticed an “out of stock” sign where the melatonin used to be. That’s because this supplement has become one of America’s most popular sleep aids, and demand spiked last year. According to an article published in Business Insider, US consumers spent more than $825 million on melatonin supplements in 2020—a whopping 42.6% increase in sales compared with 2019.

Most of us associate melatonin supplements with insomnia but researchers are looking into new uses for this wildly popular dietary supplement.

Recently, this dietary supplement has been promoted not just as a sleep aid, but as a way to prevent or treat certain chronic diseases—and some are even taking it to relieve pandemic-induced stress. But history tells us that what manufacturers claim their supplements can do doesn’t always match up with what they have been proven to do. And, because there is less FDA oversight for dietary supplements compared with OTC or prescription medications, companies could falsely advertise the quantity of melatonin in their product, according to the Business Insider article.

“Because melatonin is not [as] regulated, there’s no guarantee about the purity of what you’re buying,” said Jennifer Martin, of the American Academy of Sleep Medicine Board of Directors. “There’s no guarantee that each pill in a bottle has the same amount of melatonin in it.”

So does melatonin live up to the hype? Some studies do suggest that melatonin plays other important roles in the body beyond sleep, and it’s even being studied for its effects on COVID-19. However, more research is needed to fully understand these effects. 

Here’s what the most recent research tells us about using melatonin to improve your health.

What is melatonin?

Melatonin is a hormone secreted primarily by the pineal gland in the brain, and it helps to regulate our sleep-wake cycle (or circadian rhythm), according to the National Center for Complementary and Integrative Health (NCCIH). As a dietary supplement, melatonin can be made naturally from the pineal gland of animals, however, it is usually produced synthetically. 

Melatonin supplements are typically used as a sleep aid to provide relief for insomnia or disrupted sleep rhythms caused by jet lag or working night shifts. According to Brent Bauer, MD, of the Mayo Clinic, the supplement is “generally safe for short-term use,” with a very low likelihood of developing dependence, becoming habituated, or experiencing hangover effects, as can occur with many sleep medications.

Meanwhile, if you suffer from insomnia, here’s a look at seven steps that can improve sleep hygiene and help you conquer your sleep problems, or at least diminish their hold on you.

Does melatonin have therapeutic properties?

Recent research indicates that melatonin may help with more than just sleep. Studies in a review published in Antioxidants in 2020 have demonstrated that the hormone boasts lipophilic antioxidant properties, anti-inflammatory effects, immunomodulatory actions, and protective abilities against free radicals.

The review’s authors note that oxidative stress is a common characteristic of various metabolic, degenerative, and cardiovascular disorders, and cancer. Melatonin plays a protective role both intracellularly and extracellularly, with its abundant mitochondria, which prevent free-radical damage. 

“Melatonin has been proven to be twice as active as vitamin E, believed to be the most effective lipophilic antioxidant,” the authors wrote.

According to the review, studies have shown that reduced melatonin levels are a risk factor for various cardiovascular diseases, including ischemic myocardial injury, hypertension, atherosclerosis, and heart failure. Likewise, evidence indicates that melatonin supplementation can help reduce nocturnal hypertension, blood pressure, platelet aggregation, and circulating catecholamines. One study cited by the authors found that melatonin alleviated right ventricular hypertrophy and dysfunction, and reduced interstitial fibrosis and oxidative stress in a rat model. Strong evidence for the efficacy of melatonin as a treatment for cardiovascular diseases in humans, however, is still lacking.

Studies cited in the review have also demonstrated that melatonin may be effective against various bacterial and viral infections, due to its immunoregulatory functions and protective mechanisms against free radicals. For example, lab trials have demonstrated that melatonin can help in fighting off Staphylococcus aureus, carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and sepsis, particularly septic shock.

Melatonin can also help relieve the systemic inflammation that viruses cause. “Melatonin’s beneficial effects have been postulated against flu infections, and also against SARS-CoV-2 virus responsible for the pandemic that has hit the world in recent months,” the authors wrote, adding, “melatonin reduces inflammation and oxidative stress related to aging, cardiovascular diseases, diabetes, all conditions associated with an increased risk of mortality in patients with COVID-19 disease.” However, more research is needed to better understand the interaction between exogenous melatonin and viruses, they added. 

As for melatonin’s role in fighting COVID-19, the NCCIH notes, “Current research looking at the effects of melatonin on COVID-19 is only in the early stages. There are a few randomized controlled trials (studies evaluating melatonin in people) in progress. At this point, it is too soon to reach conclusions on whether melatonin is helpful for COVID-19.”

Beyond this, the authors note, melatonin may have neuroprotective effects via its “free radical scavenging activity,” and can even help moderate obesity, according to some studies. While further study into melatonin’s efficacy against various disorders (not related to sleep) is required, the authors concluded that melatonin supplementation in combination with traditional therapies could increase the efficiency of the treatment for infectious disorders, cardiovascular disease, cancer, and neurodegenerative disorders.

According to a review published in the International Journal of Molecular Medicine in March 2021, melatonin’s anti‑inflammatory and antioxidative functions mean that it likely serves as a protective agent against bone-related diseases, like fractures, osteoporosis, and osteoarthritis. The authors of the review point out that melatonin has been shown to increase new bone regeneration, neovascularization, and the number of osteoblast-like cells, as well as cartilage and callus, at the site of fractures.

My Daughter-in-law, Dipthi Holloway (Dipthi Samalia) is going to be featured in the Breast Cancer Pink Bun Campaign. This is a picture of her as part of the campaign. Dip is a Physiotherapist ( Otago) and Pharmacist (UQ). They have two adorable children. Dip has had Breast cancer and the full gamut of treatment. She has a steely determination and fighting spirit to overcome this set back. She has followed the treatment given by her specialists and has a very healthy lifestyle. We are all proud of her indomitable spirit and ability to remain cheerful through these difficult times.

From the BCNA website :

It’s the little things that can make a big difference to Australians affected by breast cancer. That’s why this May, Breast Cancer Network Australia (BCNA) and Bakers Delight are asking you to buy a Pink Bun during the 2021 Pink Bun campaign.

For three weeks, from 6 May – 26 May, every Bakers Delight bakery across the country will turn pink with 100 per cent of sales from ALL Fun Buns donated to BCNA.

This year’s campaign will highlight the little things that can really make a big difference throughout someone’s breast cancer diagnosis and treatment, such as support with housework, spending quality time with family and friends, or receiving messages of support.

The Pink Bun campaign is a wonderful opportunity for you to be involved with both your community and your local Bakers Delight. Whether it’s hosting a Pink Bun Party, buying a Pink Fun Bun in bakery or making a donation by purchasing a virtual 6-Pack of Pink Buns online.

Every little bit counts!

How you can support the 2021 Pink Bun campaign

For those who prefer to show your support the traditional way:

1. Buy a Pink Fun Bun or better yet a 6-Pack of Pink Buns (between Thursday 6 May and Wednesday 26 May).
2. Purchase a pink lady silhouette for a gold coin donation and write a message of support.
3. Make a donation in bakery via the donation tins on the counter, or simply ask Bakers Delight’s friendly staff to add a donation to your purchase at the register.
4. Host a Pink Bun Party fundraiser with your workplace, school, social or community group (please check and adhere to COVID-19 restrictions in your location).
5. Just pop into your local Bakers Delight bakery and say thank you to the staff for supporting BCNA.

Or show your support virtually:

1. Buy a virtual 6-Pack of Pink Buns online and send a message of support.
2. Make a donation via SMS by texting PINKBUN to 0400 662 662.
3. Host a virtual Pink Bun Party.
4. Send an email or post on social with the hashtag #PinkBunsForBCNA to say thank you to your local store and staff for supporting BCNA.

Over our 21-year partnership, Bakers Delight has raised an incredible $21 million for BCNA. Money raised this year will help BCNA continue to provide up-to-date, tailored information to the 20,825 Australians expected to be diagnosed with breast cancer this year.

To find your nearest Bakers Delight bakery, visit the Bakers Delight website.

Samantha Jones, Sex and the City

Four glamorous New York girls balanced colorful cocktails, killer shoes, and relationships in the Sex and the City TV series and movies. Even these fabulous ladies had to deal with the M-word at some point. Samantha Jones (played by Kim Cattrall), the powerful PR publicist, tackles menopause in Sex and the City 2. Armed with an arsenal of age-defying methods, Jones announces, “I am leading the way through the menopause maze with my vitamins, my melatonin sleep patches, my bio-identical estrogen cream, progesterone cream, and a touch of testosterone.”

Angelina Jolie

Angelina Jolie wrote in a New York Times op-ed that she uses bioidentical estradiol (estrogen) to help ease her early menopausal symptoms after her total abdominal hysterectomy.

Yolanda Foster

Yolanda Foster opened up on the Season 7 Real Housewives of Beverly Hills Reunion that she is not suffering from hormone decline in menopause because of bioidentical hormone replacement therapy. She uses the bioidentical hormone pellets that are inserted into the body

Siggy Flicker

Another Bravo Reality tv star and Real Housewife of New Jersey, Siggy Flicker reportedly uses this alternative form of hormone replacement therapy. Flicker enjoys bioidentical hormone replacement therapy weight loss treatment plans to reach an optimal weight and feel more energized—and she looks great! NBC reported Flicker stating her weight loss program shaved 10 lbs off her stomach—sign us up.

Suzanne Sommers

The Huffington Post reports 71-year-old Suzanne Somers using bioidentical hormone replacement therapy to look 40. Her impressive looks are also combined with her zealous and youthful demeanor

Happy World Menopause Day!

Today is World Menopause Day and we fully support the awareness and coverage it has been getting recently, with the openness of celebrities speaking about their own menopause experiences and how difficult their lives have been.

It is no longer taboo to be open about being menopausal, with some our favourite celebrities sharing their symptoms and tips from hot flushes and depression to weight gain and aches all due to falling hormone levels.

How do you know you are going through the menopause?

The average age women go through the menopause is 51 – but some symptoms can be triggered way before the menopause even begins. Take depression, for instance, pre-menopausal depression has been shown to occur as early as 10 years before the menopause.

A woman is considered to be in menopause when they have not had a menstrual cycle for 12 months, meaning she is coming to the end of her reproductive years.

Celebrity Views and Experiences

Carol Vorderman – 56

Carol’s menopausal symptoms began when she was 54, where she suffered severe mood swings.

“I had six months when I was really low. I’m not a depressed person but in that space of time, I was genuinely depressed. ..I didn’t have any of those hot sweats and all of that kind of thing. I was surprised how it hit my emotions.” She says

Getting treated?

Blood tests revealed Carol’s hormone levels were low. She explains, “It became obvious my depression was linked to the menopause. That knowledge gave me hope.”

Professor Studd prescribed Carol a balanced hormone gel which is applied to the skin – oestrogen and testosterone and a minimum amount of natural progesterone. This combination is derived from plants and more closely mimics naturally occurring hormones in the body than conventional HRT which uses oral oestrogens and contains progestogen.

On the second day of applying the gels and cream, she felt “back to her old self”.

Talking about the treatment he prescribed Carol, Professor Studd says: “The best and safest treatment is hormones through the skin – oestrogen and testosterone and the minimum amount of natural progesterone.”

“The main disadvantages are that women will still bleed every month. The traditional pill doesn’t contain progesterone. Having progesterone is good for energy, mood, depression and libido.”

Carol revealed on Twitter she took Oestrogel and Testim plus progesterone, saying: “From the moment I took it, I have never, ever felt that way.”

Lorraine Kelly, 57

The television present came out as menopausal on ‘The M Word’ segment of her talk show, ‘Lorraine’ which she hosts with Doctor Hilary Jones. Lorraine explains,  “there was no joy in my life”  and then she realised it was due to the menopause, once Dr Hillary diagnosed her and prescribed HRT she regained her joy!

Amanda Redman,

Redman speaks out about how the taboo was not discussed at home and how “hideous it was for women of our mothers’ generation – because whilst  my girlfriends and I talk about everything under the sun, including the menopause, it was something they didn’t discuss”

Amanda describes the menopause as “ghastly” and also revealed how her breasts increased in size during the menopause. She’d love a reduction – and further plastic surgery – but her husband has other ideas.

The British actress is very candid and open about the menopause “It’s embarrassing. I wish women would talk about it more as it’s not pleasant. I’ve had hot flushes and I am irritable.”

Kim Cattrall, 61 

“Literally one moment you’re fine, and then another, you feel like you’re in a vat of boiling water, and you feel like the rug has been pulled out from underneath you.”

The Sex and The City star continues, “What I would say, which I’ve said to myself and girlfriends who’ve also experienced hot flashes, in particular, is that change is part of being human. We evolve and should not fear that change. You’re not alone. I feel that part of living this long is experiencing this, so I’m trying to turn it into a very positive thing for myself, which it has been, in the sense of acceptance and tolerance and education about this time of life.”

She first discovered menopause as Samatha in Sex in the City, then a couple of years later after a sudden hot flush she went on a journey on how to deal with her menopausal symptoms and has become a voice for this very intimate issue.

The 61-year-old dealt with it by getting in tune with her body and encourages you to ‘see your doctor’ and a is an advocate of Bioidentical Hormone Replacement therapy.

Julie Walters, 67

“I still get hot flushes. That’s fifteen bloody years. Still, it’s nothing like I did then. Ripping off your nightie and Grant [her husband] thinking it’s something else! No – don’t get any ideas!”

Jennifer Saunders, 58

“It is fairly brutal and you go through all the accompanying side effects: hot flushes, weight gain, a sense of mourning for lost youth, sexiness and somehow the point in anything. I became depressed, which I ended up getting help with.”

Zoe Ball, 46

“I am hot and hairy. It’s like my last hurrah. Is it going to get better? Do I do HRT or do I have the funny tea supplement?”

When an audience member suggested she should have more sex to combat the symptoms, she replied: “OK, that’s a good tip. HRT and more sex. I’ll take that.”

Davina McCall,  50

After taking HRT, Davina said: “All my symptoms stopped overnight. I’m not endorsing it. It was a personal decision.’I feel, in a funny way, it’s almost more attractive that I can’t have children because now I don’t need to take contraception.”

She continued, ‘There’s a certain friskiness that comes about that. There is a confidence that comes with age.”

Davina also revealed that her early menopause symptoms gave her a similar feeling to quitting cold turkey from her heroin addiction.

Don’t Suffer In Silence

Let’s celebrate this natural stage of every woman’s life and be proud! It’s not something to be ignored or judged about, it’s a natural change that our bodies go through, don’t be ashamed – BE MENOPAUSAL AND PROUD! You are still you, and still beautiful.

Colette Harris, editor of Health Plus explains,

“Even though most women go through it between 45 and 55 you don’t see the likes of Madonna, Lulu, Kim Cattrall, Annie Lennox, Lorraine Kelly and Carol Vorderman ‘giving up’, putting on their housecoats and slippers and retiring from public life… It’s about time myths about menopause were well and truly shattered.”

https://2d35044eda1bb8a27da0c78f59c5abec.safeframe.googlesyndication.com/safeframe/1-0-38/html/container.html

To: Oprah Winfrey; Subject: Hormones

What I Know for Sure

Photo: Matthew Rolston
There’s a theme running through my life right now: balance. You’ve heard me speak of it many times in this column. However, I didn’t know how out of kilter I was until my friend Kate sent me the following e-mail, last July.

---

To: Oprah Winfrey
Subject: Hormones!

Kate: Have you had a blood analysis of your hormones by an expert? I feel like a new person—and I want the same for you.

Oprah: An analysis by a hormone specialist is exactly what I need. I’ve been having issues for two years that nobody can figure out. I keep asking my doctors because I highly suspect it is hormonal. Not enough doctors know or care enough about women’s hormonal issues. So yes, I need a blood analysis.

Kate: I had issues for two years too—some noticeable and some vague. Lack of focus. No zest. No drive. I felt a veil of malaise. But I now have an individualized cocktail of hormone supplements that work. I feel good on every level. Before, I was even having difficulty reading!

Oprah: I have a stack of books 2 feet high to read for summer. Haven’t cracked one yet.

Kate: Inability to read—both in terms of attention and joy—was the last straw for me!!! Okay, you’re going to my doctor—he’s a gynecologist who specializes in hormones and antiaging. He determines what hormonal levels are right for you. It is a process of discovery.

Oprah: What’s amazing is, I didn’t even think of lack of focus as a symptom. I thought my life force was being slowly drained. So just knowing there is a veil is a comfort.

---

That exchange was the beginning of my path to restoring balance—in my hormones and in every other area of my life.

When I visited the specialist Kate recommended, I came prepared, with all my blood tests from a year of thyroid exams. He took one look and said, “Your hormonal tank is empty. That is why you feel like your life force is being drained.”

My eyes welled with tears. Finally someone understood and had a solution.

He gave me a prescription, then ordered more tests. And after one day on bioidentical estrogen, I felt the veil lift. [Traditional hormone therapy uses estrogen from the urine of pregnant horses. Bioidentical estrogen is chemically identical to that made by women’s ovaries.] After three days, the sky was bluer, my brain was no longer fuzzy, my memory was sharper. I was literally singing and had a skip in my step.

For more than two years, I hadn’t gotten a decent night’s sleep. I’d had heart palpitations. These are symptoms of hyperthyroidism. But even after my thyroid was balanced, I was still having “surges”—like a rush of adrenaline throughout the night that kept me awake.

And equally important were the other, seemingly unrelated, symptoms.

I started talking to more friends in their 40s and 50s, and soon we were all aha’ing each other. This is what some described: Anxiety. Fatigue. Low-grade depression. Lack of confidence, curiosity, drive, ambition. A sense of being overwhelmed. Feeling flat and dead and afraid. A general feeling of malaise.

I share my story in hopes of opening the door to restoration and balance to women (and men) everywhere. I do so knowing that bioidentical hormone therapy is controversial and, to many people, confusing.

I encourage you to take charge of your health, read this month’s story on menopause, and research the best doctors for you. Most important to me is getting past the sense of shame. As Kate later wrote, “I thought my symptoms were a failing in my character. I blamed myself—never knowing that these were real symptoms that indicate a hormonal imbalance.”

To every woman who’s ever felt the same: What you need to know for sure is that you’re not alone.

Let’s start the conversation—and lift the veil.

Read the full story on hormone therapy
Read more: https://www.oprah.com/spirit/what-oprah-knows-for-sure-about-menopause-and-hormones#ixzz6sWLPeB7U

This is one of the most important books on women’s hormones I have ever read. The reason it is so important, is the background of Dr Bluming – a cancer researcher on HRT for most of his life. His wife has had breast cancer, so he has a personal interest in the subject. He confirms all the things that I have been saying about the benefit of Estrogen to women and explains how safe it is to use in women who have had breast cancer. I have given Estrogen to women with a history of breast cancer many times, with a full explanation of the risks/benefits involved. A consent form must be signed that they have been fully informed and understand what they are doing.

I recommend all of you with an interest in menopause and whether to take HRT or not – to read this book. It is such major decision for women and their future well-being. I still get so many women being told by their doctors to stop the HRT (and often reprimanded by them as well) and when they do so go into a downward spiral. Their doctor may have a superficial knowledge of HRT, whereas I have been deeply engaged in studying women’s hormones for the last 25 years- who would you rather believe? My regular blogs and website are an effort to keep women UpToDate with the latest research. I bought my copy online from Booktopia.

A compelling defense of Hormone Replacement Therapy, exposing the faulty science behind its fall from prominence and empowering readers to make informed decisions about their health.

For years, hormone replacement therapy (HRT) was hailed as a miracle. Study after study showed that HRT, if initiated at the onset of menopause, could ease symptoms ranging from hot flashes to memory loss; reduce the risk of heart disease, Alzheimer’s, osteoporosis, and some cancers; and even extend a woman’s overall life expectancy. But when a large study by the Women’s Health Initiative announced results showing an uptick in breast cancer among women taking HRT, the winds shifted abruptly, and HRT, officially deemed a carcinogen, was abandoned.

As it turns out, however, that study was seriously flawed. Now, sixteen years after HRT was left for dead, Dr. Bluming, a medical oncologist, and Dr. Tavris, a social psychologist, track its strange history and present a compelling case for its resurrection. They investigate what led the public—and much of the medical establishment—to accept the Women’s Health Initiative’s often exaggerated claims, while also providing a fuller picture of the science that supports HRT.

A sobering and revelatory read, Estrogen Matters sets the record straight on this beneficial treatment, and provides a path to wellness for women everywhere.

Praise for 
Estrogen Matters:


“I hope Estrogen Matters draws enough attention to counter the fears and misinformation about HRT that so many women, and their physicians, still hold.” ― Phyllis Greenberger, MSW, former President and CEO of the Society for Women’s Health Research

“Well written, insightful, and hard hitting,Estrogen Matters successfully rebuts the billion-dollar, government-led study known as the Women’s Health Initiative, which claimed that hormones for post-menopausal women are harmful. That study was wrong. It turns out estrogens do matter for women’s health.” — Vincent T. DeVita Jr., MD, Professor of Medicine, Yale School of Public Health and Yale Cancer Center
“If you’re one of the many menopausal women who avoid HRT to treat your symptoms because of all the scary headlines, this book is a must-read.” — Jennifer Ouellette, author of Me, Myself and Why

More praise ︎

About the Authors

AVRUM BLUMING, MD
Avrum Bluming received his MD from the Columbia College of Physicians and Surgeons. He spent four years as a senior investigator for the National Cancer Institute and for two of those years was director of the Lymphoma Treatment Center in Kampala, Uganda. He organized the first study of lumpectomy for the treatment of breast cancer in Southern California in 1978, and for more than two decades he has been studying the benefits and risks of hormone replacement therapy administered to women with a history of breast cancer. Dr. Bluming has served as a clinical professor of medicine at USC and has been an invited speaker at the Royal College of Physicians in London and the Pasteur Institute in Paris. He was elected to mastership in the American College of Physicians, an honor accorded to only five hundred of the over one hundred thousand board-certified internists in this country.
CAROL TAVRIS, PhD

Carol Tavris received her PhD in social psychology from the University of Michigan. Her books include Mistakes Were Made (But Not by Me), with Elliot Aronson; Anger: The Misunderstood Emotion, and The Mismeasure of Woman. She has written articles, op-eds, and book reviews on topics in psychological science for a wide array of publications — including the Los Angeles Times, the New York Times Book Review, the Wall Street Journal, and the TLS — and a column, “The Gadfly,” for Skeptic magazine. She is a fellow of the Association for Psychological Science and has received numerous awards for her efforts to promote gender equality, science, and skepticism.

All those women on hormone treatment should read this very thorough up[date on where we are now as regards HRT. Note that there are many misconceptions and ill-informed people (unfortunately doctors as well) about these developments. I sometimes feel like an old time prophet, because all the things I have said about menopausal treatment of women have now come to pass. It is just unfortunate that so many women had to suffer needlessly, and some still do today, due to this incorrect understanding of the benefits and safety of HRT. Please read this, and pass on to your doctors if they are unaware of the contents of this article.

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Reviews

Hormone replacement therapy – where are we now?

R. D. Langer , H. N. Hodis , R. A. Lobo & M. A. Allison Pages 3-10 | Received 17 Sep 2020, Accepted 04 Nov 2020, Published online: 06 Jan 2021

Abstract

Hormone replacement therapy (HRT) was the standard of care for menopause management until 2002, when perceptions changed following release of the initial results from the Women’s Health Initiative (WHI) trial. Fears of breast cancer and heart attacks engendered by that report were not supported by the data, especially for recently menopausal women. Clinically, HRT is usually initiated near menopause. The WHI tested something different – the effects of HRT started a decade or more after menopause. As it turned out, age at starting HRT is critical in determining benefit/risk. HRT use plummeted following the WHI in 2002 and has remained low, prompting strong interest in alternative treatments. None provide the range of benefits across multiple organ systems offered by estrogen. Most have concerning adverse effects in their own right. HRT can provide effective relief for a wide range of health conditions, potentially avoiding the need for multiple treatments for separate problems. Unfortunately, among many women and clinicians, the perception of HRT benefit/risk is distorted, and its use avoided, leading to unnecessary distress. Following the WHI, many clinicians have not received adequate training to feel comfortable prescribing HRT. When initiated within 10 years of menopause, HRT reduces all-cause mortality and risks of coronary disease, osteoporosis, and dementias.

摘要

自2002年在妇女健康倡议(WHI)试验的初步结果公布后, 激素替代疗法成为更年期的管理标准, 人们对于激素的看法发生了变化。该报告引发的对乳腺癌和心脏病发作的担忧没有数据支持, 尤其是对近期绝经的妇女。临床上, HRT通常在绝经前开始。WHI测试了一些不同的东西——绝经后使用激素替代治疗十年或更长时间的效果。事实证明, 开始激素替代治疗的年龄是决定效益/风险的关键。继2002年WHI风潮后, 激素替代治疗的使用量大幅下降, 并且一直保持在较低水平, 这引发了人们对替代疗法的浓厚兴趣。大多数激素都有其自身的不利影响, 没有一种药物能像雌激素那样对多器官系统产生广泛的益处。激素替代治疗可以有效缓解各种健康状况, 潜在地避免了对不同疾病的多重治疗。不幸的是, 在许多女性和临床医生避免激素的使用, 激素替代疗法的益处/风险的被扭曲了, 并且导致了不必要的痛苦。继WHI之后, 许多临床医生还没有接受足够的培训来适应使用激素替代疗法。在绝经10年内开始使用激素替代疗法降低了全因死亡率和冠心病、骨质疏松症和痴呆症的风险。

Keywords: Hormone replacement therapymenopause managementvasomotor symptomswomen’s healthcoronary heart diseaseosteoporosisgenitourinary syndrome of menopausebreast cancerPrevious articleView issue table of contentsNext article

HRT in the context of contemporary options for menopause management

For the majority of women seeking relief of menopausal symptoms, the perceived harms of hormone replacement therapy (HRT) are exaggerated, while the perceived benefits of alternative therapies are overstated, and their risks either ignored or underestimated ¹ . There is robust evidence that estrogen is a highly effective treatment for menopausal vasomotor symptoms ² and the genitourinary syndrome of menopause ³ . When initiated before the age of 60 years (or roughly within 10 years of menopause), HRT is effective in reducing all-cause mortality ^4–8 . In that age range, HRT prevents coronary heart disease (CHD) ^{4 , 5 , 9 , 10} . Moreover, HRT prevents hip fractures ¹¹ , an important and underappreciated cause of morbidity and mortality in postmenopausal women. Nonetheless, HRT use dropped precipitously between 2001 and 2008, following the initial publication of the Women’s Health Initiative (WHI) trial of conjugated equine estrogens (CEE) + medroxyprogesterone acetate (MPA) in 2002, decreasing from approximately 43% to 11% of women aged 45–74 years ^{12 , 13} .

Fear of HRT among women, and misunderstanding of the risk/benefit, along with lack of appropriate education among providers, has led to underutilization, unnecessary suffering, and excess chronic disease and mortality in postmenopausal women over the past two decades ^14–17 . Why is this disconnect so prevalent and persistent?

Fear of breast cancer

When asked to rank health concerns, women and health-care providers consistently place breast cancer at the top of the list ^{18 , 19} . Use of HRT has been associated with both decreases and increases in breast cancer, with associations varying by the form of HRT, dose, and duration of use ²⁰ . In initial reports from the largest clinical trial to address the question, the WHI, use of CEE-alone reduced the risk of breast cancer although the results were not statistically significant ²¹ , while use of CEE + MPA was associated with an increase in breast cancer that was also not statistically significant ²² . Subsequent analyses found significant reductions in invasive breast cancer among adherent women taking CEE-alone ²³ . In the most recent reprise of those analyses by the WHI group, CEE-alone significantly reduced the risk of breast cancer by 22%, while CEE + MPA increased the risk by 28% in analyses not adjusted for covariates ²⁴ . Notably, in the only analysis of these data including protocol-specified adjustment for covariates, the breast cancer risk for CEE + MPA was not statistically significant ²⁵ . Even had the breast cancer association for CEE + MPA been significant, it was rare, affecting approximately one woman for every 1200 woman-years of treatment ²² . These contrasts are mirrored in reports from large observational cohorts reflecting use of estradiol and a variety of progestogens, where micronized progesterone was associated with no risk, while elevated associations for synthetic progestins varied by class ^{26 , 27} . These findings for breast cancer imply that the progestogen component modulates the effect of estrogens, and suggest that the breast cancer risk is dependent on the specific treatment used, with the progestogen component, used to protect the endometrium, being pivotal.

The vast majority of published reports on HRT and breast cancer come from observational studies that are subject to a variety of biases and residual confounding. Virtually all of these were combined in a collaborative publication in 2019 involving 58 observational studies with 568,859 women and 108,647 cases of invasive breast cancer. Modeling initiation at age 50 years and 5 years of use, and combining all forms of estrogens and all forms of progestogens, continuous HRT, sequential HRT, and estrogen alone were associated with, respectively, 2, 1.4, and 0.5 excess cases of breast cancer per 100 women over 20 years ²⁸ . These numbers translate into 1.0, 0.7, and 0.25 excess cases per 1000 woman-years; a rare adverse event using World Health Organization criteria ²⁹ . Importantly, the median year for a breast cancer diagnosis was 2005 so that the treatments evaluated have largely been replaced by newer regimens over the past two decades. Although excluded from the main paper, the Collaborative Group did report a combined analysis of results from randomized clinical trials. Aggregating data for estrogen alone from five clinical trials other than the WHI, representing approximately 2850 woman-years of use and 17,000 woman-years of follow-up, yielded a non-significant 39% reduced hazard ratio (0.61; 95% confidence interval [CI] 0.34–1.09) ²⁸ . The parallel data from four clinical trials representing about 13,350 woman-years of exposure and 30,500 woman-years of follow-up yielded a 14%, also non-significant, increased risk of breast cancer for estrogen plus progestogen, 1.14 (95% CI 0.78–1.65). The latter is substantially lower than the pooled relative risk from the observational studies, which exceeded a hazard ratio of 2 ²⁸ . The contrasts between the results of the randomized trials and the observational data underscore the reliability issues of less rigorous study designs ²⁰ .

Misunderstanding of the associations between age, HRT, and cardiovascular risk

The second major area of confusion is the effect of HRT on incident cardiovascular disease (CVD), particularly CHD and stroke. Again, the largest clinical trial to address this question is the WHI trial. As with breast cancer, the WHI trials of CEE-alone and CEE + MPA demonstrated different findings for CVD. Age and time since menopause when HRT was initiated emerged as an important confounding factor that was not recognized when the WHI was designed. A primary goal of the WHI was to evaluate HRT in older women well past menopause because the weight of evidence available when the study was planned strongly suggested that HRT had a favorable benefit/risk ratio when initiated near the time of menopause. Accordingly, the WHI enrolled primarily women well beyond menopause (mean age 63 years, mean time since menopause 12 years), with only 30% of the cohort <60 years of age ^30–32 .

In the WHI CEE-alone trial overall, among women aged 50–79 years at baseline there were non-significant results for CHD (9% reduction) and stroke (39% increase), with a priori adjustment for multiple comparisons ²¹ . In contrast, among women aged 50–59 years, there was a statistically significant 40% reduction in a composite endpoint of CHD and related coronary diagnoses ⁹ , and there was no increase in stroke ²¹ . In the WHI CEE + MPA trial among women aged 50–79 years at baseline, there were non-significant results for CHD (29% increase) and stroke (41% increase) with a priori adjustment for multiple comparisons ²² . Similar to the CEE-alone trial, in women within 10 years of menopause, there was a non-significant 11% decrease in CHD, a parallel non-significant reduction in CHD in women aged 50–59 years with vasomotor symptoms ³³ , and a non-significant increase in stroke in women aged 50–59 years ¹¹ . The Danish Osteoporosis Study evaluated a composite endpoint of hospitalized heart failure, myocardial infarction, and death in 1006 women aged 45–58 years (mean 7 months postmenopausal). Women with a uterus were randomized to estradiol with norethisterone acetate or no treatment, while women with prior hysterectomy received estradiol or no treatment. After 10 years, the composite endpoint was significantly reduced by 52% with HRT and there was no effect on stroke ¹⁰ . The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized secondary prevention trial of CEE + MPA in older postmenopausal women (mean age 67 years) with pre-existing CHD. In the HERS, CEE + MPA increased myocardial infarction in the first year of treatment, suggesting that HRT increased plaque rupture. Over the subsequent 4 years, there was a statistically significant reduction in CHD with HRT relative to placebo ³⁴ . HERS findings indicate that HRT acted early on rupture-susceptible plaque, resulting in myocardial infarction within the first year of treatment. Viewed in context with the WHI results that demonstrated opposite effects for HRT initiated within 10 years of menopause, or >10 years after, these findings imply that HRT introduced in the presence of atheroma can trigger plaque rupture ³⁵ . These findings led to the recognition that timing of initiation relative to the health of the endothelium is key to the vascular effects of HRT, the ‘timing hypothesis’ ^{36 , 37} .

The 7-year Early vs. Late Intervention Trial with Estradiol (ELITE) is the only clinical trial to directly test the ‘timing hypothesis’. It tested oral micronized estradiol 1 mg daily (plus micronized progesterone vaginal gel in women with an intact uterus) versus placebo in healthy women who were <6 years or >10 years past menopause when randomized. The ELITE found reduced progression of subclinical atherosclerosis (carotid artery intima-media thickness) in women who were <6 years postmenopausal, but no benefit in women >10 years past menopause (p for interaction = 0.007) ³⁸ . The timing hypothesis was also studied using the Finnish nationwide death registry (1994–2009) comprising 489,105 postmenopausal women with 3.3 million years of HRT exposure; CHD death was evaluated among HRT users according to age at initiation. The CHD standardized mortality ratio was lower among women who initiated estradiol alone or estradiol/progestogen therapy at age <60 years compared to those initiating at older ages. HRT reduced the risk of all-cause mortality in a nearly linear relationship with duration of exposure ⁷ . With this in mind, it should be noted that the WHI CEE + MPA trial included 1298 women with pre-existing CVD. The effects of HRT in women with pre-existing CVD could have confounded the CHD results, giving the impression that CEE + MPA increased CHD in primary prevention. A stratified analysis of WHI women by baseline CVD to determine the effects of HRT on CHD in women with and without pre-existing CVD is conspicuously missing from the literature.

Meta-analyses of clinical trial data stratified by either age or time since menopause show that HRT may decrease CHD and all-cause mortality by 30–48% when initiated in women <60 years of age and/or <10 years since menopause ^{4 , 5 , 39 , 40} . A Bayesian meta-analysis of HRT and all-cause mortality in younger postmenopausal women (mean age 55 years) showed a similar 22–27% reduction in all-cause mortality across randomized clinical trials and observational studies ⁴⁰ . A Cochrane systematic review found that in women initiating HRT at <60 years old and/or <10 years since menopause, CHD risk was reduced by roughly half (relative risk [RR] 0.52; 95% CI 0.29–0.96) and all-cause mortality by 30% (RR 0.70; 95% CI 0.52–0.95) ⁵ . In contrast, in women initiating HRT when >60 years of age and/or >10 years since menopause, HRT had no effect on CHD or all-cause mortality. Venous thromboembolism was significantly increased, but there was no evidence of an excess risk of stroke with HRT.

Prevention of fractures

Estrogen is a potent modifier of bone metabolism and menopause is associated with a rapid loss of bone mineral density (BMD) and a downstream increase in fracture risk. Nearly all trials testing interventions to prevent osteoporotic fracture have been conducted in women with osteopenia or osteoporosis. The Postmenopausal Estrogen Progestins Interventions (PEPI) trial and the WHI are unusual in having evaluated HRT for effects on bone health in women unselected for fracture risk. The PEPI trial enrolled 875 women aged 45–64 years (mean 56 years), and within 10 years of menopause, in a 3-year trial comparing treatment with CEE-alone, CEE + MPA daily, CEE + MPA sequentially, or CEE + micronized progesterone sequentially versus placebo on a range of metabolic factors ⁴¹ . All active regimens provided increases of about 2% and 5% in BMD at the hip and spine, respectively, and there were no statistically significant differences between regimens ⁴² . The WHI went further in assessing not just BMD but also fracture rates. In women on average 7 years older than PEPI participants (mean age 63 years), both the WHI CEE-alone and CEE + MPA trials found a somewhat greater 3-year increase in hip BMD, approximately 3.5% versus placebo ^{43 , 44} . Overall, the WHI showed consistent benefits for both CEE-alone and CEE + MPA, with a 33% reduction in hip fracture, the most catastrophic outcome of osteoporosis, with either CEE-alone or CEE + MPA. Vertebral fractures were significantly reduced by 36% and 32%, respectively, in the two trials and a composite outcome of all fractures was reduced by approximately 25% ¹¹ .

The effects of estrogen in major organ systems and contrasts with other pharmacotherapy

Estrogen has important metabolic effects in most major organ systems. It normalizes the vaginal and urethral environment ³ , positively influences arterial blood flow ⁴⁵ and subclinical atherosclerosis ^{37 , 38} , promotes a non-atherogenic lipid profile ⁴¹ , reduces rates of incident diabetes mellitus ⁴⁶ , helps to prevent bone loss and may restore lost bone ⁴⁷ , limits excess osteoclastic activity ⁴⁸ , and maintains neuronal health in the central nervous system and spine by promoting growth and mitigating inflammation ⁴⁹ . The flight away from HRT has resulted in the increased use of individual drugs to prevent or treat the effects of decreased endogenous estrogen. For instance, statins are given for the prevention of coronary disease. Bisphosphonates, selective estrogen receptor modulators, receptor activator of nuclear factor-κΒ ligand inhibitors, and a variety of other strategies are used for bone loss, and selective serotonin reuptake inhibitors are used for hot flushes. None provide the physiologic spectrum of end organ effects delivered by estrogen. All are associated with their own adverse effect profiles.

Whereas HRT in close proximity to menopause reduces CHD and all-cause mortality, in women lipid-lowering with statin therapy has a null effect on CHD in primary prevention, and a null effect on all-cause mortality in primary and secondary prevention ⁵⁰ . Unlike HRT, which reduces new-onset diabetes mellitus, statin therapy increases the risk of incident diabetes particularly among postmenopausal women ⁵⁰ . Additionally, a signal for increased risk of breast cancer in women randomized to statin therapy relative to placebo has been reported in at least four randomized controlled trials ^51–54 . Other cardiovascular medications are linked to breast cancer at an even greater degree than that reported for HRT. For example, calcium channel blockers used predominantly for hypertension and angina have been shown to statistically significantly increase the risk for ductal breast cancer (RR = 2.4) and lobular breast cancer (RR = 2.6), compared to risk ratios typically <1.3 reported for the association between HRT and breast cancer ⁵⁵ . Unlike HRT, bisphosphonates have been associated with fractures (specifically femoral shaft atypical spiral fractures and mandibular necrosis), atrial fibrillation, and cardiovascular mortality ^56–58 . While HRT is the most effective therapy for ameliorating hot flushes, selective serotonin reuptake inhibitors maximally reduce flushing up to 50% while being associated with increased fracture risk ^{59 , 60} .

Dementia

Prior to the WHI, several large observational studies found that HRT was associated with reduced rates of Alzheimer’s disease and other dementias ^61–63 . The WHI Memory Study (WHIMS) was added to address this question during the main trial with the critical caveat that only women aged 65 years and older were enrolled. The rationale was that dementia incidence rates are too low in women under 65 years old for an effect to have been detected during a primary trial period of roughly 8 years. Rather than finding benefit, the WHIMS found an increased rate of mild cognitive impairment and dementias in women over 65 years old randomized to either CEE-alone or CEE + MPA ^{64 , 65} . However, those findings, like the unanticipated increase in cardiovascular events in women aged >60 years when HRT was initiated in the WHI trials, may be explained by the reversal of estrogen benefits when replacement is initiated late, as described in detail earlier. In the 18-year follow-up of the WHI, considering the entire cohort with an average age of 63 years at baseline, use of CEE with or without MPA was associated with a significant reduction in mortality attributed to dementias. The association was strongest for CEE-alone ⁸ . In the Women’s Estrogen for Stroke Trial (WEST), after 3 years of treatment with estradiol, women with cerebrovascular disease and a normal Mini-Mental State Examination at randomization had lower rates of cognitive decline (RR = 0.46; 95% CI 0.24–0.87) relative to women with an abnormal Mini-Mental State Examination at entry ⁶⁶ .

Contemporary views and knowledge of HRT

Based on the non-significant findings for increased breast cancer and CHD in the CEE + MPA arm of the WHI, the US Food and Drug Administration (FDA) placed a black-box warning on all HRT regimens in 2002 that has remained essentially unchanged despite the emergence of data to the contrary cited earlier, including the opposing findings for both outcomes in the CEE-alone parallel trial. That decision, together with the unprecedented and sustained attention to the initial WHI results in the popular press, caused a dramatic exodus away from not just the use of HRT, but from education in clinical training. The results of this cascade of events, predicated on a widely misunderstood evidence base, have led to a profoundly unscientific situation in contemporary medicine. It has led to the rise in use of unproven treatments for menopausal symptoms, many of them not regulated and carrying their own risks. It has led to a great disconnect between the evidence and beliefs among women who are potential candidates for HRT. It has also led to a generation of clinicians who are inadequately trained in evaluating a patient’s risk/benefit for HRT, or managing it. The absence of education in this area has resulted in some clinicians adopting the negative perspective of the general press and not remaining abreast of the literature. As a result, many physicians do not include it in their practice, denying the opportunity of treatment with HRT to women who would be appropriate candidates.

In the USA, the lack of accurate understanding of HRT risk/benefit has also led to pharmacy formulary decisions by insurance plans that create substantial financial barriers to treatment even for women with clinicians willing to prescribe HRT. On one of the most widely held insurance plans in the USA, a monthly course of HRT costs approximately $200 ⁶⁷ . In contrast, the combined cost of a monthly course of atorvastatin for coronary prevention, along with alendronate for osteopenia, is under $10 ⁶⁷ . Costs are similar with other major insurance plans in the USA. As documented earlier, the combined adverse effect profile of statins and bisphosphonates appears worse than that of CEE-alone, and presumably that of CEE with a metabolically mild progestogen. Thus, there is a strong incentive for the use of multiple drugs whose mechanisms are not physiological like estrogen, with increased adverse effects, for the prevention of diseases that are physiologically addressed by restoring effective levels of estrogen.

The rise in popularity of transdermal estrogens

In parallel with the increase in complementary and alternative treatments for menopause, there has been an increase in the forms and regimens available for HRT. The largest change has been the movement away from oral estrogens in favor of transdermal products. Within the category of transdermal products, there has been a rise in popularity of compounded ‘bioidentical estrogens’ that are not approved by regulatory authorities. Besides estradiol, compounded products may include estrone and estriol, as well as progestogens and androgens in combination. Medical societies have consistently advised against these products. Although marketed as ‘natural’, they are in fact synthesized in laboratories ⁶⁸ . They are unregulated, the hormones delivered are not consistent, and some of the hormones included do not have an indication. The assertion by advocates that these formulations are safer is also without foundation. Indeed, there is evidence that bioidentical estrogen products have caused endometrial cancer ⁶⁹ .

However, pharmaceutical-grade, FDA-approved, ‘bioidentical’ transdermal estradiol is available as a patch or gel. It is important to note that transdermal estrogens are exclusively estradiol, while there are a variety of oral preparations available, with the most data available for CEE (a mix of estrogens, dominated by estrone sulfate and equilin sulfate, with minimal estradiol content). Other commonly available oral estrogen preparations for use in menopause include estradiol, esterified estrogens, and estropipate. In contrast to estradiol, and to some degree other oral estrogen preparations, the metabolic conversion of the mixed estrogens in CEE results in the circulation of estrogens with a variety of receptor affinities, and estrogen receptor agonism and antagonism, or selective estrogen receptor modulator-like activity.

Increasing use of transdermal estrogens was driven initially by observational data suggesting a lower risk of thrombotic complications ⁷⁰ . Transdermal preparations can also be more convenient for the patient in that patches are placed once or twice weekly, while oral estrogen must be taken daily. Combination patches with estrogen plus progestogen are available on some formularies. Otherwise, for women with a uterus, this advantage in convenience is reduced because a progestogen must be taken daily. Transdermal gels and creams also require daily administration and are less popular than patches. A report from the WHI Observational Study of 93,676 postmenopausal women found non-significant trends for lower rates of CHD, stroke, and cardiovascular mortality, but not all-cause mortality, for transdermal estradiol compared to oral CEE ⁷¹ . In a US matched-cohort study of health insurance claims between 1999 and 2011, transdermal estrogen preparations were associated with a lower incidence of cardiovascular complications (including CHD, angina, heart failure, stroke, transient ischemic attacks, pulmonary embolism, and other venous thromboembolisms) compared with oral estrogen preparations: incidence rate ratio 0.81 (95% CI 0.67–0.99), irrespective of the type of estrogen used ⁷² . Two large case–control studies in the UK found that oral HRT regimens were associated with increased venous thromboembolism while transdermal use was not. CEE was associated with a higher risk than estradiol. Within the oral regimens, CEE + MPA had the highest risk while estradiol + dydrogesterone had the lowest ⁷³ .

Clinical trial data on transdermal estrogens are limited to relatively small studies, typically with fewer than 1000 participants. Results are available for intermediate markers rather than differences in disease rates. The Kronos Early Estrogen Prevention Study (KEEPS) evaluated progression of carotid artery intima-media thickness with transdermal estrogen (estradiol 50 μg/day), low-dose oral estrogen (CEE 0.45 mg/day), and placebo over 4 years in 727 healthy newly menopausal women. There were no significant differences in carotid artery intima-media thickness between treatment groups ⁷⁴ .

An early observational report also suggested a lower risk of breast cancer with transdermal estrogen ²⁶ . However, a later report in the same population found that estrogen alone was associated with increased risk (RR 1.29; 95% CI 1.02–1.65) and that the progestogen component modulated this risk with non-significant associations for estrogen with micronized progesterone (RR 1.00; 95% CI 0.83–1.22) and for estrogen–dydrogesterone (RR 1.16; 95% CI 0.94–1.43), but a significant association for estrogen combined with other progestogens (RR 1.69; 95% CI 1.50–1.91) ²⁷ .

Contrasts between outcomes with various progestogens

The only role for progestogens in menopausal therapy is to protect against endometrial hyperplasia and endometrial cancer. Accordingly, progestogens are not indicated for women who have had a hysterectomy. All clinical trials and most observational studies that have evaluated multiple progestogens have found important differences in their metabolic effects and in disease outcomes. The PEPI trial found that micronized progesterone taken sequentially and MPA taken either daily or sequentially provided effective endometrial protection. CEE-alone and CEE with micronized progesterone had similar effects in raising high-density lipoprotein cholesterol that were superior to CEE + MPA. Likewise, CEE-alone and CEE with micronized progesterone had no effect on 2-h post-challenge glucose, while CEE + MPA caused a mild increase ⁴¹ . Nonetheless, in both the WHI trial and the HERS, CEE-based regimens including CEE + MPA reduced incident type 2 diabetes ^{11 , 75} . A meta-analysis of 107 HRT randomized controlled trials provides strong evidence that HRT statistically significantly reduces new-onset diabetes mellitus ⁴⁶ .

Perhaps the most clinically important differences in progestogens are the effects in breast tissue. A clinical trial in 71 postmenopausal women evaluated sequential CEE + MPA, or transdermal estradiol with sequential micronized progesterone (TDE + MP), over two cycles. CEE + MPA significantly increased cell proliferation measured using Ki-67/MIB nuclear antigen expression compared with baseline (p = 0.003) and compared with TDE + MP (p = 0.05). TDE + MP did not significantly increase cell proliferation ⁷⁶ . These data are consistent with a longer-term experiment conducted in oophorectomized cynomolgus monkeys. In this model, estradiol plus progesterone did not significantly increase proliferation in breast epithelial cells (p = 0.47 for lobular cells and p = 0.72 for ductal cells) compared with placebo, measured using Ki-67 expression. In contrast, estradiol + MPA significantly increased lobular cell proliferation by 194% (p = 0.009) and ductal proliferation by 544% (p = 0.006) versus placebo ⁷⁷ .

Contemporary HRT as a therapeutic option for menopause management

Each woman must be assessed in the context of her unique presentation of concerns and physical findings. For women seeking relief of vasomotor symptoms, estrogen is the most effective treatment although other strategies may work. For a woman presenting with vasomotor symptoms plus other issues (e.g. genitourinary syndrome of menopause, osteopenia), HRT becomes increasingly more useful as a single modality that can manage multiple conditions. Even in the absence of significant vasomotor symptoms, HRT is a good option for healthy women within 10 years of menopause who may be at higher risk for chronic diseases ⁷⁸ . HRT can meaningfully improve quality of life, and this contrasts sharply with other products that are not estrogen-based ⁷⁹ . Contemporary options include CEE, oral estradiol, and transdermal estradiol, each in a variety of doses that can be titrated to achieve treatment goals. CEE-alone reduced breast cancer in the WHI. For women with a uterus, micronized progesterone has a more favorable metabolic profile, and a reduced proliferative effect in the breast, than MPA. Dydrogesterone, norethisterone, and drospirenone are other options, although there are no head-to-head comparative outcome data versus other progestogens.

The clinical trial data indicate that, for women starting HRT before age 60 years, or within 10 years of menopause, all-cause mortality is reduced. CHD risk may be reduced depending upon the treatment regimen, fracture risk will be reduced, and there may be protection against dementia. Some women will experience the return of vasomotor symptoms and genitourinary syndrome of menopause after stopping HRT, as well as rapid bone loss, even at ages well beyond 60 years. Risks, including those for vascular events and fracture, return when effective treatment is stopped ^{14 , 16 , 17} . Accordingly, there are no reasons to place mandatory limitations on the duration of MHT, conditioned upon ongoing individualized reassessment of benefit and risk for each woman using HRT ⁶⁸ .

A pooled analysis of three studies of nonpharmacological interventions for menopausal hot flashes

Avis, Nancy E., PhD¹; Levine, Beverly J., PhD¹; Danhauer, Suzanne, PhD¹; Coeytaux, Remy R., MD, PhD²Menopause: April 2019 – Volume 26 – Issue 4 – p 350–356 doi: 10.1097/GME.0000000000001255 Original Articles Buy

Objective: The aim of the study was to conduct a pooled analysis of three published trials of nonpharmacological interventions for menopausal hot flashes to compare the effectiveness of interventions.

Methods: Data from three randomized controlled trials of interventions for hot flashes (two acupuncture trials, one yoga trial) were pooled. All three studies recruited perimenopausal or postmenopausal women experiencing ≥4 hot flashes/d on average. The primary outcome for all three studies was frequency of hot flashes as measured by the Daily Diary of Hot Flashes. Study 1 participants were randomly assigned to 8 weeks of acupuncture treatments (active intervention), sham acupuncture (attention control), or usual care. Study 2 participants were randomly assigned to 10 weeks of yoga classes, health and wellness education classes (attention control), or waitlist control. Study 3 randomly assigned participants to 6 months of acupuncture or waitlist control. To standardize the time frame for these analyses, only the first 8 weeks of intervention from all three studies were used.

Results: The three active interventions and the two attention control groups had statistically similar trends in the percentage reduction of hot flashes over 8 weeks, ranging from 35% to 40%. These five groups did not differ significantly from each other, but all showed significantly greater reduction in hot flash frequency compared with the three usual care/waitlist groups.

Conclusion: Acupuncture, yoga, and health and wellness education classes all demonstrated statistically similar effectiveness in reduction of hot flash frequency compared with controls.

The common activity that’s worsening your health

Alistair Gardiner|March 30, 2021

In today’s working world, many of us are sitting most of the day in front of our computer—especially with the shift to telemedicine appointments. Research indicates that those in office-based professions spend 70%-85% of their workday seated—and all of that sitting is detrimental to our cardiovascular, metabolic, and mental health, according to a recent study published in BMC Musculoskeletal Disorders.

Sitting for prolonged periods of time is worse for your health than you think.

The pandemic has made matters worse. Reports point to decreases in physical activity in general since the virus prompted lockdown restrictions and stay-at-home orders. One study found that more than 40% of US adults were sitting for more than 8 hours a day during April 2020. 

Does so much sitting really translate to worse health? How does it affect the body and the mind? Here’s how this sedentary lifestyle changes us, according to the latest research.ADVERTISEMENT -SCROLL TO KEEP READING

The health impacts of being sedentary  

Evidence suggests that not using our bodies for long periods of time takes a toll on our well-being. Prolonged periods of sitting have been linked to metabolic disorders like increased blood pressure, high blood sugar, obesity, and high cholesterol levels, according to the Mayo Clinic. Extensive periods of sitting are also associated with an increased risk of cardiovascular disease and cancer mortality. 

A review published in The Lancet found that those who sit for more than 8 hours a day with no physical activity had a mortality risk similar to that caused by obesity and smoking.  

According to the BMC article, prolonged sitting is also associated with type 2 diabetes incidence and all-cause mortality. Other studies have demonstrated that sitting can lead to musculoskeletal problems such as neck and shoulder pain.

Why you should get moving

The good news? Countering these negative effects is simple, at least in theory. You need to stay active. The authors of the aforementioned Lancet study analyzed data from more than 1 million subjects and found that those who engage in 60-75 minutes of moderate-to-intense physical activity a day effectively ameliorated the adverse outcomes of prolonged sitting. 

Other research has found that even just replacing some of your sitting time with standing can help. One review published in Mayo Clinic Proceedings examined nine clinical trials focused on the effects of standing rather than sitting on factors including fasting blood glucose, fasting insulin, and lipid levels; blood pressure; body fat mass; weight; and waist circumference. The average difference in standing time between the control group and the intervention group was 1.33 hours per day. While they didn’t observe major differences in every outcome measured, researchers did find that those who spent more time standing had significantly lower body fat mass values and fasting blood glucose levels. They concluded that replacing a few hours of sitting with standing could be used as an adjunctive intervention to help mitigate cardiovascular risk factors and assist in preventing diabetes. 

Similarly, the BMC review concluded that breaking up periods of prolonged sitting with standing or light exercises could help mitigate the ill effects of too much sitting. The review examined the range of physiological mechanisms affected by sitting for too long and hypothesized that some of these factors may be affecting cognitive function.

Researchers analyzed studies that showed how long periods of sitting increase hyperglycemia, autonomic stability, inflammation, adverse hormonal changes, and restrictions in cerebral blood flow. Together, the researchers argued, these factors may negatively affect cognitive performance. 

Intermittent standing or low-to-moderate physical activity may improve cognitive function by mitigating the adverse vascular and hormonal changes that result from too much sitting, they found. Breaking up prolonged periods of sitting was shown to have positive effects on postprandial hyperglycemia, insulin resistance, inflammatory markers, the regulation of hormones like cortisol, and cortical and peripheral arterial blood flow. The authors linked all of these mechanisms to possible improvements to cognitive function. 

Movement guidelines

To mitigate the risks of too much sitting, experts advise following the US government’s Physical Activity Guidelines for Americans, which states that everyone should get a minimum of 150 minutes of physical activity per week. 

Beyond this, we should take a break from sitting every 30 minutes and find ways to fit in more standing and walking throughout the day, according to the Mayo Clinic. Tips include: Stand while you talk on the phone or watch TV; try working at a standing desk; hold “walking meetings” with colleagues, rather than sitting around a conference table; or (for the adventurous) set up a treadmill at your workstation, so you can stay active throughout the day.

If you need an extra push, you might find some useful tips in the findings of a study published in BMJ, which analyzed the impact of a multicomponent intervention to reduce sitting time. Subjects received a height-adjustable workstation, informational seminars and training sessions, and even a vibrating timer-cushion to remind the subjects that they’d been sitting for too long. Researchers found that, after 1 year, those in the intervention group were sitting for an average of 83 minutes fewer per day than the control group. Additionally, subjects in the intervention group reported improvements in job performance, work engagement, occupational fatigue, daily anxiety, and quality of life.

For those who find themselves sitting for prolonged periods, the evidence suggests you should probably swap out your current workstation for a standing desk, and if you’ve got a day of pencil-pushing and keyboard tapping ahead, make sure you take regular breaks.

For more ideas on combating sedentary behavior, click here

. 2016 Jun;19(3):249-51. doi: 10.1080/13697137.2016.1175237. Epub 2016 Apr 14.

Withdrawal of hormone therapy and increased risk of cardiovascular disease

A Pines  ¹ Affiliations

• PMID: 27075839
• DOI: 10.1080/13697137.2016.1175237

Abstract

Many menopause specialists follow the principle of prescribing postmenopausal hormone therapy (HT) for the shortest duration needed, in order to decrease the risk of some related serious adverse effects, such as breast cancer. Based on several large studies, it seems, however, that withdrawal of HT may be associated with immediate, though small increased risk of coronary heart disease and stroke. Cessation of HT correlates with increased risk of fractures as well. This information should be relayed to hormone users while discussing the continuation of HT with their health-care provider, but, since the potential cardiovascular harm is actually very small, it should not deter symptomatic women from using HT when needed.