Menopause is diagnosed retrospectively after 12 months of amenorrhea, with perimenopause beginning when cycle length changes by at least 7 days or menopause-related symptoms appear; routine hormone testing is not recommended as FSH levels are variable and unreliable for diagnosis. Systemic hormone therapy (MHT) is the most effective treatment for vasomotor symptoms and should be offered as first-line therapy to symptomatic patients without contraindications, with benefits outweighing risks for those with early menopause or premature ovarian insufficiency (POI). Contraindications include undiagnosed vaginal bleeding, active or history of breast cancer, and active liver disease. Non-hormonal alternatives like SSRIs, SNRIs, and gabapentin are available for patients with contraindications or preferences. Common myths include MHT causing weight gain (it only affects fat distribution, not overall weight), MHT preventing muscle loss (changes are negligible), and bioidentical hormones being safer (they are not scientifically distinct from approved hormones).
Deep Dive
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Deep Dive
Women's Health Part 3: Menopause Matters: Diagnosis, Management and Myths.. Dr. Alexandra Seal-GrantAdded:
Good afternoon everyone. Welcome to the first webinar of our women's health and focus webinar series hosted by the office of lifelong learning and physician learning program here at the University of Alberta. My name is Denise Campbell Sharon. I'm the associate dean of the office. Our office is committed to providing reliable updates and resources for clinicians, health care professionals, and everyone committed to providing best clinical care for patients.
The University of Alberta, its buildings, labs, research stations are primarily located on the territory of the Nihao, Nitsatipi, Matei, Nakota, Deni, Haronash, and Anesnav lands that are now known as parts of treaties 6, 7, and 8 in the homeland of the Matei. The University of Alberta respects the sovereignty, lands, histories, languages, knowledge systems, and cultures of all First Nations, Matei, and Inuit nations.
So, I'd like to start with a little bit of housekeeping information for today's webinar. Uh, if you have any questions about technical difficulties or L3 programs or services, please use the chat feature at the bottom of the screen. If you have questions for our speaker, please use the Q&A feature of the webinar. Please review what's already been asked and upvote those questions you'd really like to have answered. We cannot guarantee that we'll be able to get to all of your questions.
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So today we're so uh pleased to welcome Dr. Nick Porier and Dr. Alexandra Seal Grant. Dr. Porier is a eurog gynecologist at the Lois Hole Hospital and the physician lead for the women's health and focus webinar series. She's been instrumental in planning the sessions and coordinating topics and we're deeply grateful to her for her leadership and her support. And our speaker today is Dr. Alexandra CL Grant uh who's going to share with us common myths um in menopause care and will review the diagnosis and symptoms of pmenopause and menopause and provide us with some pearls in the treatment options for vasom motor symptoms. We're so grateful to you Dr. Sel Grant. Um, so Alexander went to medical school here at the University of Alberta and she completed her family medicine residency at Delhausy University and she says she accidentally became a menopause specialist after sitting next to two strangers at a conference and they encouraged her to apply for a job at Great Menopause Clinic now uh at the Lakewood Community Health Center Menopause Clinic. She used she earned her Menopause Society certified practitioner credential soon after she she started working here. So, thank you so much to you both and thank you to everyone for coming out today and I'm going to turn it over to you.
All right, I'll just get my slides up here.
All right, so I'm really excited to see how many people are here today. Thank you so much for taking the time out of your busy schedules to make this topic a priority for your learning. In terms of disclosures, I have previously received speaking fees from Night Therapeutics. I don't have any other financial disclosures.
My objectives for today are to go over the diagnosis and symptoms of pmenopause and menopause, the diagnosis and health implications of premature ovarian insufficiency and early menopause, treatment options for vasa motor symptoms, common myths in menopause care, and some practical resources.
I'm sure that for those of you who've been in practice for a while, you've found that more and more patients are asking about menopause. And I think overall that's a good thing. But I know that a lot of people feel kind of unprepared to address all the questions that are coming up. So hopefully this will help.
I know that there are a lot of barriers to providing menopause care. Uh traditionally there hasn't been enough training for clinicians, but I'm really happy to say that this is improving. It can be difficult as well to figure out which symptoms are related to age, menopause, or other conditions. Patients often have biases biases, either positive or negative ones, about hormone therapy before they even talk to you.
Um, these can be based on online misinformation or anecdotes from friends and family. And counseling patients on this can take a really long time.
So that's why I'm very excited to share that there is now a provincial menopause and pmenopause clinical pathway. Um and so like many of the other pathways, it starts with an algorithm, but we weren't able to fit it all into one page. So it's actually a two-page algorithm followed by all of the expanded details.
And if you click on one of the boxes in the algorithm, it will take you directly to the section with more details on that topic.
Uh you can access it by scanning this QR code and it's also available on Alberta's pathway hub.
There's also a patient pathway to go along with it. So this is what the first page of it looks like. So just like the clinical pathway, it starts with a summary and then it's followed by expanded details and it covers a lot of the same content as the clinical pathway. And we did have some patients from Alberta who were involved in helping us to develop this pathway and make sure that it seemed useful to them.
It's available on myhealth.alalberta.ca.
There's also a link to it in the clinical pathway and there's a QR code that you can scan to find the patient pathway.
There are two main hormones that I'll be talking the most about today um including estrogens and progesterrogens.
So estrogen isn't a single type of hormone. There are multiple different ones, both naturally occurring ones and synthetic ones. And estrogens are the main hormones that treat vasa motor symptoms and some other common symptoms of menopause and pmenopause.
Progesterrogens are generally used to prevent endometrial hyperplasia and endometrial cancer in patients who are taking systemic estrogen.
So now we'll get into the diagnosis and symptoms of menopause and pmenopause starting with a case. So Jennifer A is 51 and she has palpitations and night sweats. Her last period was 13 months ago and she says, "I think it's menopause. Can you check my hormones?"
So what tests do you order? Do you do a cardiac workup and malignancy workup? Do you check some hormone levels? Do you do all of those things or none of those things?
Okay. So, good. So, we have a mix of answers there.
We'll get into my thoughts on this soon.
Uh, but first, we have one more question about the same patient. So, would you offer her hormone therapy assuming that she's otherwise healthy?
Sorry, just one second here.
Okay, mix of answers as well, but it sounds like most of you would.
Now, I'm going to change the case slightly. It's still a 51-year-old woman with palpitations and night sweats, but would you offer her hormone therapy if she hadn't fully stopped having periods yet? She was just having irregular periods and her last one was only 2 months ago instead of 13.
Okay, so a slim majority still would, but a lot of people are not so sure about that.
Okay. So, hopefully I can help you to clarify a little bit about how to figure out what's really related to menopause or not. The reality is that it's not always going to be black and white. Um, but there are some ways of trying to approach this issue.
So, pmenopause starts when there are changes in cycle length of at least 7 days between consecutive cycles or other menopause related symptoms. Perry menopause ends 12 months after the final menstrual period. Menopause is diagnosed retrospectively after 12 months of amenorhea. This slide has a lot of information. The only thing I really wanted to highlight here is if you look in the section on supportive criteria where they show different hormone levels, you can see that at many stages FSH levels are going to be really variable. So, it's not often going to be a reliable test to make the diagnosis or to predict when someone's going to go through menopause.
So, the diagnosis is usually clinical based on menstrual pattern and possibly associated symptoms. And if we can't rely on someone's periods because maybe they have a hormonal IUD or they've had a hyctomy, then we have to rely more on symptoms. The typical age of menopause is 45 to 55, but pmenopause symptoms may start up to 10 years before the final menstrual period. That being said, other diagnoses should be considered, especially under age 40.
Routine hormone testing is not recommended unless you suspect premature ovarian insufficiency or early menopause. Testing hormone in levels in other situations is often misleading and it often delays appropriate management.
This is a straightforward symptom questionnaire that's really practical to use in a primary care setting. It's available at mq6.ca and we also have links to it in our pathway and it was developed by Dr. Susan Goldstein, a family physician from Ontario. It asks about changes in periods, hot flashes, vaginal dryness, pain or sexual concerns, bladder issues or incontinents, sleep changes, and mood changes.
This is a much more detailed symptom list that's available on the Menopause Foundation of Canada website, and it was endorsed by the Canadian Menopause Society. Um, and this is something that you can look back at if a patient brings up a symptom and you're really unsure if it could be menopause related. um if it's on this list, there's a chance that it's related. Now, if something is on this list, it doesn't necessarily mean that it will get better with hormone therapy. Uh it's really going to depend on the symptom.
The differential diagnosis is a bit complicated because it's going to depend a lot on which symptom we're talking about. Um but table one in the menopause pathway does have a list of some investigations to consider and the rationale for them. Um right at the top I've put obstructive sleep apnea and iron deficiency because those are two very common things that often cause overlapping symptoms with menopause and pmenopause.
Um, other things to think about would be hypo or hyperyroidism, chronic insomnia, mood disorders, PCOS, hypercalcemia, cardiovascular disease, malignancy, hyperp prolactinmia, medications such as opioids or high doses of anti-depressants, fiochromocyto, and carcinoid syndrome.
Here's my suggested approach if you're not really sure whether or not a symptom is related to menopause or pmenopause.
First thing you really need to do is um just like you normally would assess whether there are any red flags present.
So for example, if someone has night sweats and unintentional weight loss, you need to investigate for other causes rather than assuming that those night sweats are menopause related. If there are no red flags, you can consider offering a 3-month trial of menopause hormone therapy to see if those symptoms improve. Or you can use a non hormonal medication if there are any contraindications to hormone therapy. If I'm offering this hormone therapy trial, I'll typically go with a standard dose.
But if I have a patient who's older or a bit more sensitive to medication side effects, I might try a lower dose. Just keep in mind that that can take a bit longer to start working or it might be a bit less effective. Um, I would also recommend reaching out to a specialist for advice if you're really unsure.
So, we'll talk a little bit about what vasa motor symptoms are. So they include hot flashes and night sweats and they can start up to 10 years before menopause. They last an average of about 7 and 1/2 years but 15% of patients will have them for over 15 years. Overall about 80% of women will have phasom motor symptoms at some point with menopause and 20% will have severe ones.
So, getting back to Jennifer A, who's our um patient who has palpitations and night sweats, you explain that her symptoms are typical of menopause. You offer her treatment and you tell her that you'll order more tests if her symptoms don't improve. So, Jennifer A goes home and then you meet Jennifer B.
Um, a typical day for me in the menopause clinic usually involves seeing at least a couple patients with the same name cuz they're all the same age. And Jennifer was the most popular baby name in Canada 51 years ago. So, Jennifer B is 41. She hasn't had a period in 15 months, and she feels well, but she tells you that she saw a doctor who told her that she was lucky that she wasn't having periods anymore. But then she read online that she should be on hormones, and she's scared of taking hormone therapy because she heard that it causes breast cancer. What should she do? Should she do nothing? Should she take hormone therapy for up to 5 years?
Should she take hormone therapy for at least 10 years?
Okay, so a mix of answers. Most people thought that she didn't need to do anything, followed by people who thought she should maybe take at least 10 years of hormone therapy, and some people thought maybe some short-term hormone therapy.
Okay, so we'll talk now about early menopause and premature ovarian insufficiency.
Early menopause is when the final menstrual period is before age 45. This affects about 3 to 12% of the population. Premature ovarian insufficiency or POI is when the final period is before age 40 and this affects about 1 to 4% of the population.
Ovulation can still occur intermittently. So keep this diagnosis in mind for anyone under 40 whose cycles become irregular.
These conditions really matter because they actually have significant negative health implications including a reduced life expectancy mainly because of cardiac disease. Um some of the other most significant health risks that I discuss with patients are increased risks of osteoporosis and dementia.
uh systemic hormone therapy reduces the risks associated with early menopause and POI.
So to make the diagnosis, an elevated FSH above 25 after 4 months of amenorhea supports a POI diagnosis in someone under 40. Early menopause would be confirmed after 12 months of amenorhea in patients under 45, but it's reasonable to suspect it and go ahead and start treating after several months of amenorhea with an elevated FSH and no other cause for amenorhea. You definitely don't need to wait a full 12 months to treat these patients. If you do the initial set of labs and they're normal, I would recommend repeating them after 4 to 6 weeks because there may still be some fluctuations in hormone levels and you might have just caught them at the wrong time.
A low estradiol level also supports these diagnoses, but there isn't a specific cutoff. And then other tests that would be recommended to rule out common causes of secondary amenorhea would include TSH, prolactin, and beta hCG.
Referral to an endocrinologist or menopause specialist is strongly recommended if POI is suspected and should also be considered in early menopause.
So if there are no contraindications, systemic hormone replacement therapy is recommended until the average age of menopause, which is around 51 and a half. Hormone therapy can be continued longer if it's still needed for symptom management.
Highdose HRT or continuous birth control pill would be recommended until age 51 to 52 and then you can either reduce the dose or stop depending on the patient's individual needs. the target estrogen doses that we use in POI and early menopause are higher than for other patients. Um, and if they're on a higher estrogen dose, they also need a higher progesterrogen dose. The Canadian Menopause Society has an equivalency table on their website that has recommended doses for all of the forms of estrogen that are available in Canada. And there is a link to it in the algorithm in the pathway.
In this population, we use the term hormone replacement therapy because we're replacing the hormones that they should still have. Otherwise, the term menopause hormone therapy or menopausal hormone therapy is used instead. To make things confusing, in the UK, they refer to MHT as HRT. Ultimately, I really don't care which term you use. I'm never going to give you a hard time for picking the wrong one. I just want to explain why there might be differences in the terminology that I use in these slides.
So, don't forget about contraception.
Overall, about 25% of people with POI will have at least one spontaneous return of ovulation. So, if they don't want to get pregnant, they should continue contraception until 2 years after their final period.
So, getting back to Jennifer B, she was our 41-year-old patient with um over a year of amenorhea. You explained that systemic HRT is recommended until the average age of menopause to protect her bones, heart, and brain, and she's interested in starting HRT. Jennifer B goes home, and then you meet Jennifer C.
She's 51, and her last period was 2 years ago. She's been told that she can't take hormone therapy because she has hypertension, which is well treated, and she smokes, but she has unbearable hot flashes. What do you recommend?
Should she quit smoking? Try clonedine, try systemic MHT, or maybe a combination of those things.
Okay, so a mix of answers there, but I'm glad to see that at least most of the answers involved one of the combinations that included quitting smoking.
So now we'll get into the treatment of vasa motor symptoms. Before we talk about medications, I'll briefly go over some non-farmacological interventions.
There is good evidence for cognitive behavioral therapy, clinical hypnosis, and smoking sessation. There's insufficient evidence for mindfulness-based interventions, paste respiration, relaxation, cooling techniques, exercise, and yoga. You know, exercise might be great for some other menopause related symptoms, but it's just not specifically recommended for vasa motor symptoms.
Systemic hormone therapy is safest if it's started under age 60 or within 10 years of the final menstrual period. It can be continued beyond that age or time frame. And there is no age limit or treatment duration limit for continuing systemic MHT if it's still needed for symptom relief and there are no contraindications.
It should be stopped if there is a contraindication or if it's no longer needed for symptom management. There's no evidence on whether it's better to stop abruptly or gradually. So I generally give my patients the choice.
For older patients who are on oral estrogen after age 60, consider switching them to transermal estrogen.
uh and I'll explain why later on.
The main benefits are that it's the most effective treatment for vasa motor symptoms. Uh systemic hormone therapy also helps to prevent bone loss especially if it's started in pmenopause or early postmenopause. It's less likely to be helpful if you're starting it in someone whose last period was 8 years ago. By then they've already had most of that initial menopause related bone loss. MHT may also help with sleep disturbances and muscle and joint pain.
It may help with mood and anxiety symptoms in perry menopause and it may help with genital urinary symptoms but local vaginal hormones are more appropriate if genital urinary symptoms are the main concern and some patients who are on systemic hormones may also need the addition of some vaginal hormones. Um and the webinar coming up on March 10th will focus on these symptoms.
The risks are a bit complicated because they vary depending on the type, dose, duration of use, route of administration, timing of initiation, and whether a progesterrogen is used.
Starting hormone therapy more than 10 years after the final period or at an age older than 60. Um, it's less favorable and the risks may outweigh the benefits because of higher risks of coronary artery disease, stroke, venus throbo embolism, and dementia.
Cardiovascular risk gets a bit complicated because HRT reduces the risk in patients with early menopause and POI. MHT is neutral or possibly slightly beneficial for cardiovascular risk in most patients under 60 who went through menopause at the average age. That being said, it might increase the risk in some patients in that age group if they have multiple cardiovascular risk factors.
And then MHT may increase cardiovascular risk when it started in patients over 60.
Breast cancer risk um there's overall no significant risk increase in the first 5 years of taking MHT and then after that the risk is around nine additional cases per 10,000 person years of therapy.
That's similar to the breast cancer risk associated with low physical activity or two glasses of wine per day. The risk is higher with estrogen plus a progesterrogen compared to estrogen alone and with synthetic progesterines compared to natural progesterone. In the Women's Health Initiative, which was a large randomized control trial of hormone therapy um from over 20 years ago, conjugated ecoin estrogen on its own was actually associated with a decreased breast cancer risk compared to placebo. Um but we don't know as much about the risks and benefits of other types of estrogen like estradiol or estrol. Um and we also don't know as much about you know how that you know riskto benefit balance might change with increasing duration of estrogen alone.
So the bottom line is that for someone with early menopause or POI the benefits outweigh the risks even if they're asymptomatic as long as there are no contraindications.
For your more average patient starting hormone therapy in their 40s or 50s, the benefit to risk ratio is pretty neutral.
So you can treat based on symptoms. And then for someone over 60 and more than 10 years after the final period, the risks would likely outweigh the benefits in terms of starting hormone therapy, but it is okay to continue if it was started before that. And these recommendations apply to systemic hormone therapy, not vaginal hormone therapy.
There's a great two-page summary of this information for patients available on the Menopause Society website and there is a link to it in the patient pathway as well.
Now, I'll go over the contra indications to systemic estrogen. And again, these do not apply to vaginal estrogen.
They're specific to systemic estrogen.
They include undiagnosed vaginal bleeding, active breast cancer or personal history of breast cancer, known or suspected estrogen dependent cancers such as endometrial or ovarian. Now, there may be some exceptions. There are a few cancer types in those categories where it might still be suitable to prescribe hormone therapy, but you should always check with a specialist first. Active liver disease is a contra indication. Now I know that fatty liver is incredibly common and if someone with fatty liver has normal liver enzymes it's okay to prescribe hormone therapy coronary artery disease active or history of stroke active or history of venus throbo embolism. Um with that history it might be reasonable to talk to a hematologist because some patients can still take hormone therapy but it might be recommended for them to also take anti-coagulants at the same time.
Um the same recommendation would apply to anyone who maybe hasn't had a blood clot but they have a known thrombophilia. And finally pregnancy is also a contra indication.
Systemic progesterrogens have a couple of contraindications as well including undiagnosed abnormal vaginal bleeding or active breast cancer or personal history of breast cancer.
There's some other things to consider that are not contraindications, but that would be reasons to choose transermal estrogen rather than oral. Um, and if someone has a high cardiovascular risk, for example, you calculate their Framingham risk score and it comes back high, it's possible that MHT might increase their cardiovascular risk a bit higher. Um so some conditions to consider as reasons to pick transermal estrogen would be diabetes, metabolic syndrome, migraine, fatty liver, dysipidemia, malabsorption, gallstones, obesity, smoking and hypertension.
Family history breast cancer is very common and there is some reassuring observational evidence suggesting that hormone therapy doesn't further increase the breast cancer risk in those with a family history. And so MHT can be offered to patients with a family history of breast cancer. Some might still choose non hormonal medications and that's fine, but if they're interested in hormone therapy, you can offer it to them. You may want to use a breast cancer risk calculator and there are many different ones that you can find online to help you to figure out what you should be doing in terms of screening and to get an idea of that patient's baseline risk. You can also consider getting advice from a menopause specialist on the safest MHT options for a patient who has a family history of breast cancer.
So most people who go on systemic hormone therapy will be on estrogen and a progesterrogen. That's because estrogen treats their symptoms, but it can also promote endometrial growth.
Progesterrogens inhibit endometrial growth. After a hyerectomy, you don't usually need to prescribe a progesterrogen, but you should consider that if someone does have a history of endometriosis.
In Canada, we have estrogens available orally or as transermal patches or gels.
And then progesterrogens are usually taken orally, but the Marina IUD can also be used. Um, we even though it can be used longer for other indications, it should be replaced every 5 years if it's being used for endometrial protection.
And at this point, the Marina is the only hormonal IUD that has good good evidence for endometrial protection with MHT.
There are also a couple of combination products that have both hormones in them, either in pill or patch form.
There's a unique medication called Tibolone, and it's a selective tissue estrogenic activity regulator. It's been available in other countries for decades, and we've had it in Canada for a few years now. It's an oral prod drug that has estrogenic, progesterrogenic, and androgenic effects, and it does not require a separate progesterrogen, and it's considered breast neutral.
Another unique medication is the tissue selective estrogen complex. That's a pill combining conjugated ecoin estrogen, and basifine.
Basadoxifene is a selective estrogen receptor modulator or a ser similar to relaxine or temoxifen. Um, every serm acts a little bit differently, but essentially a serum will be an estrogen agonist on some tissues and and an estrogen antagonist on others. So, basodoxifene has estrogen agonist effects on bone and estrogen antagonist effects on breast and endometrial tissue. It does not require a separate progesterrogen because basodoxifene provides enough endometrial protection and this medication is considered breastneutral and it is being studied for possible breast cancer risk reduction.
I've mentioned earlier a couple times how there are some situations where I might recommend transdermal rather than oral estrogen. So in terms of cost, oral estrogen is generally less expensive.
When you look at the thrombotic risk, oral estrogen is riskier than transdermal. The impact on lipids is kind of mixed. Oral estrogen does have some beneficial effects on HDL, LDL, and total cholesterol, but it can increase triglycerides.
Transermal estrogen doesn't increase HDL, but it has less of an increase on triglycerides.
Oral estrogen can have a negative impact on libido by increasing levels of sex hormone binding globulin, which makes testosterone less available to tissues.
The risk of gallstones and pancreatitis is higher with oral estrogen. And then if you're looking to have really stable estrogen levels, for example, in someone who's prone to migraines, transdermal estrogen will give you more stability compared to oral. Some other considerations would be that oral estrogen is really easy to use. Most patients are able to swallow pills. Um, and most of the especially a lot of the older research was done on oral estrogen. Um, some special considerations with transdermal estrogen would be that some people are sensitive to the adhesives in the patch. Some brands of patches don't stick very well and then gels can transfer to other people and they are dangerous for cats to lick.
A special patient population would be those who are on GLP-1 receptor agonists. There's a helpful statement from the British Menopause Society summarizing some recommendations um that are based on expert opinion and data on birth control pills. They recommend using transdermal estrogen rather than oral. And then for the progesterrogen, they suggest either using the merina or an estrogen progesterine patch or if using an oral progesterrogen, consider doubling the dose of it for 1 month after any dose increase of the GLP-1 medication. I know that one of my colleagues just gets her patients to double their progesterrogen dose longterm, and that might be a more straightforward instruction to follow.
In perry menopause, you can absolutely prescribe MHT, but it's not going to provide contraception and it's not generally going to help with heavy or irregular bleeding and in fact, it can make bleeding worse. So, a birth control pill can be a better option for many patients in pmenopause. I usually go with continuous or extended cycles to minimize hormone-free days. Um, and My Health Alberta has a really nice article for patients summarizing how to do this.
The type of estrogen in the pill may have an impact on perry menopause symptoms. So you can try one of the pills with ethanol estradiol or the one with estrol to see if there's a difference for that patient. And then some people will actually still get menopause symptoms in spite of taking a birth control pill. So if it's appropriate, you might want to consider switching them to MHT because some people will have better symptom relief with those forms of estrogen. Another good option in perry menopause would be a merina along with some MHT estrogen.
Earlier on in the menopause transition, if you have someone who's still having relatively regular periods, but they're starting to get symptoms, then I would usually recommend starting with a birth control pill rather than MHT and it could either be a combined birth control pill or the drossperone progesterine only pill because both of those will suppress ovulation.
In these patients, hormone fluctuations are often the main driver of their symptoms rather than low estrogen levels. Um, if you use the drossperone progesterine only pill, you can add some MHT estrogen if there are symptoms that persist. This combination is off label, but I it should provide adequate endometrial protection because in the birth control form of drossperone, it's a 4 milligram pill and in the MHT combination pills that use drossperone, it's just 1 millig.
Now we'll go over the non hormonal medications. These are less effective than hormone therapy, but some of the newer ones are actually getting pretty close. They're all off label except for feesant and Ellen's Anitant. And these are good options for someone who has contraindications or who prefers not to take hormone therapy.
So, clonedine only gets a slide because it does still get prescribed pretty often, but it's no longer recommended in the guidelines because it has minimal benefit and high likelihood of side effects. We just have better options now.
SSRIs and SNRIs are both reasonable to try. You can try any medication in these classes, but they tend to help the most with vasomoter symptoms in the lower end of the dosing range and they can actually worsen vasa motor symptoms with higher doses. Some of the other symptoms that they may help with would include mood, anxiety or sleep problems.
Gabapentin is another good option and it can be given at bedtime or in two or three doses per day depending on the timing of symptoms and tolerability. The usual dose range for this purpose would be between 300 and 900 mg per day, but you can go higher if the patient tolerates it really well. In addition to helping with vasomoter symptoms, it may also help with muscularkeeletal pain and sleep.
Oxybutin can work well for vasomoter symptoms as well, but its use is limited by anticolinergic side effects. It can help with overactive bladder, but there are better medication options for this.
So if overactive bladder is a major concern for someone, I would recommend choosing one of the other medications and you can find some recommendations in the provincial pathway on female urinary incontinents.
So now I'll talk about a couple of new medications. The neurokin B antagonists.
So Kissepin, neurokinine B and dinorphine neurons or candy neurons act on the hypothalamic thermmorreulatory center. Hyperactivity of candy neurons triggers vasa motor symptoms. Estrogen inhibits candy neurons. Neurokin B stimulates candy neurons. So neurokinine B antagonists can treat vasa motor symptoms when candy neurons become more active in the absence of estrogen.
Phzylinotant was the first non hormonal medication developed specifically for vasom motor symptoms and it's a 45 mgram pill. Because of rare reports of elevated liver enzymes, you are required to monitor liver enzymes regularly during the first nine months of treatment. Uh luckily so far all of these liver enzyme elevations have been reversible.
Contra indications would include hypersensitivity, cerosis, severe renal impairment, use of a moderate or strong SIP 1A2 inhibitor, or known or suspected pregnancy.
Ellen Xanotant was approved by Health Canada last year and it is expected to be available inarmacies soon. It comes in a 120 milligram dose but it's actually two 60 mg capsules specifically so that patients can take 60 milligs per day while they're on ariththramy.
Liver enzyme monitoring is not currently required for this medication and it has been studied in breast cancer survivors.
Now even though fezzelinotant hasn't been studied in breast cancer survivors there's nothing about the mechanism of action that would be concerning in terms of breast cancer recurrence and so I think it's still reasonable to offer either of these medications to someone with a breast cancer history.
Contraindications to elen xanitant include hypersensitivity use of a strong sip 3a4 inhibitor or a known or suspected pregnancy.
At this time, it's not recommended to combine neurokin and B receptor antagonists with systemic MHT because this combination hasn't been studied, but you can combine systemic MHT with the other non hormonal medications.
So, getting back to Jennifer C, she was our post-menopausal patient who has hypertension and she smokes. You start her on transdermal estrogen and oral progesterone. You recommend smoking sessation, but she isn't ready to quit.
And that's okay. you don't need to take away her hormone therapy.
Okay, so now I'm going to go through some quick myths here. Most of these are based on things that I've seen a lot in my clinic. Um, but I do need to give credit to a couple of online mythbusters who've written some great articles on some of these topics and some of my slides came very much from their presentations or their um their articles that they've written. So Dr. Jen Gunter and Dr. Lauren Kenzo Simple did a lot of work for these slides as well.
So, in all of these cases, it's a 52-year-old post-menopausal woman named Jennifer.
Jennifer is gaining weight. She tells you that she's eating the same and that her activity levels are the same as they always have been. She wants to take MHT to help with weight loss. Will it help?
Okay, most of you got that one right.
The answer is no.
Uh, so MHT does have a minor impact on fat distribution in terms of leading to a decrease in central atyposity and visceral fat, but it has no direct impact on overall weight. The weight gain that occurs with menopause is mainly age and lifestyle related.
Treating any sleep disruption may also be helpful for weight. MHT will sometimes help with that, but uh it doesn't consistently help with sleep, so other approaches like CBT for insomnia may be helpful.
Jennifer's hair is getting thinner. She wants to start MHT to help with this. Is it likely to help?
Okay. So again, you are appropriately pessimistic here.
Estrogen therapy has not shown a consistent benefit for hair loss in post-menopausal women. So if you have a patient who's really concerned about hair loss, send them to a dermatologist.
Not to me.
Jennifer is doing well on systemic and vaginal hormone therapy. Her friend goes to a different clinic that routinely prescribes testosterone. After hearing about that, she looked it up online and found videos from physicians on social media promoting its benefits for several different symptoms. What do you tell her? I don't have a poll for this one.
Just think about it.
So testosterone can be used off label in post-menopausal women with hypoactive sexual desire disorder, but it's really important to address other contributing factors. Consider doing an e-conult or a phone consult if you're planning to prescribe testosterone. I recommend um addressing psychosocial factors and optimizing the rest of their hormone therapy first. And testosterone does not have evidence for sarcopenia, osteoporosis, mood changes, brain fog, well-being, or other symptoms.
I won't read through all this, but this slide just shows that there are so many factors besides hormones that are associated with sexual dysfunction.
And this slide just shows how a lot of other menopause symptoms can have a negative impact on sexual desire. So, treating those symptoms can be really beneficial.
Jennifer heard that private clinics offer compounded bio identical hormone therapy. They promote it as being a safer, more customized way of balancing hormones. She wants to know if it's worth the cost. What do you tell her?
Again, no poll here. Just think about it.
So, bioididentical is not a scientific term. It's a marketing term and it's used to portray compounded hormones as being more natural or safer compared to Health Canada approved hormones. Um, but uh the compoundingies that make custom compounded hormones, they're actually using exactly the same hormones that pharmaceutical companies use in their products. Um, they don't have some special more natural source of these hormones. They're all still semiynthetic. And when a hormone therapy is compounded, it's not monitored for purity and safety. The dosing can be inconsistent. It doesn't have to come with a product monograph warning someone of the risks. Um, and so my recommendation would be that if you have someone who really prefers to be on hormones that are chemically identical to their own hormones, go with one of the Health Canada approved hormone therapies that contains 17 beta beta estradiol and micronized progesterone.
This isn't necessarily going to be better or safer than synthetic hormones.
For many people, it will be, but ultimately it depends on your patients individual context.
Jennifer heard that menopause accelerates muscle loss. She wants to start MHT for muscle maintenance. Will it help?
Okay, again I agree with most of you.
No, it will not help.
So changes in lean mass are negligible over 6 years in women aged 50 to 59. The decrease in lean mass during the menopause transition aligns with the age- related decline that men have at the same age. and estrogen-based hormone therapy does not prevent muscle loss.
Jennifer wants to take testosterone to support muscle growth and maintenance.
will appropriately dose testosterone, meaning that you're keeping it in the range that it should be for a woman.
Will that support this goal?
Good. Once again, the pessimists are right about this one.
So there's no association between testosterone levels and lean mass or strength in women. Highdosese testosterone can can increase muscle size and strength. But the doses required to achieve those effects are associated with a high likelihood of side effects including excess body and facial hair, voice deepening, male pattern hair loss, weight gain, and acne. Ironically, a lot of influencers promote testosterone for weight loss in women. Um, but a lot of the studies even done on lowd dose testosterone showed one to two kilos of weight gain.
Jennifer heard that there was a study showing that testosterone prevents fractures in women. Is there good evidence for this?
Good. So, most of you said no, and I agreed. So, the study that came out recently that's gotten publicity for this wasn't designed appropriately to draw any conclusions about testosterone and fractures. Uh, it was a retrospective study and in my opinion, the biggest flaw is that it didn't control for estrogen use. And it's pretty likely that most of the patients on testosterone were also on estrogen, which would have helped to prevent fractures. There's no information on the testosterone doses that were taken, and no information on activity levels either.
Jennifer follows an influencer who promotes estrogen face cream for wrinkle prevention. The influencer says that it's been studied and it's perfectly safe. Would you prescribe it for her?
And before I share the answer, I'm going to give my personal opinion, which is that I think it's totally okay to have wrinkles. You don't need to spend your whole life looking like a 20-year-old.
That being said, I know that this is a priority for some people. Um, and so I will still share the answer, and I'm not judging you if you do care about wrinkles. That's just my own personal opinion there.
So, at this point, you know, it's plausible that estrogen face cream could be safe and effective, but we just don't have enough information to say that. The studies done on it so far have had small numbers of patients, short follow-up periods, and sometimes they didn't even have a placebo arm. Different products were used in the studies and we can't extrapolate the results from one type or dose of estrogen to another one. And the studies have not adequately assessed systemic absorption and endometrial safety.
Risks may include melasma, endometrial cancer, venus thrombism, and breast cancer. But we just don't know how to quantify those risks because we don't know enough about absorption.
And does it even work? Well, the studies have shown mixed results. There was actually a study of primer and vaginal cream on the face that showed deeper wrinkles compared to placebo, possibly because of thickening of the skin. There was another study that showed improvements in areas that were assessed by dermatologists, but then in the outcomes that were reported by the study participants themselves, they couldn't notice a difference in their skin compared to placebo. The study stated that excellent ratings were given to all products referring to estriol cream, estradiol cream, and placebo cream. So then why wouldn't you just use the placebo cream? Um the way this study is written is quite funny. If you look at the table that they have on outcomes reported by patients, it's in a very small font and they made it only take up half the page and all their other tables that had more positive outcomes are much larger. And this study was not published in a peer-reviewed journal. It was a sponsored clinical report. And this is a study that's being cited by many of the on online influencers who are telling your patients that they should use estrogen face cream.
There was a review in a dermatology journal last year that summarized this well, saying that essentially the evidence for topical estrogen is strongest at the hisytological and molecular level, but the responses are not uniform. Actual clinical outcomes haven't lined up with the hisystological findings and most controlled trials didn't demonstrate reproducible improvements in visible aging and the safety data are still inconclusive.
So, for now, I would recommend sticking with treatments that have more evidence and safety data like sunscreen, hats, sun avoidance, retinoids, exfoliants, and avoiding smoking.
Okay, we've almost made it. That was a lot of information. I'm going to just summarize a few things and leave you with some resources and then we'll get to questions.
HRT is recommended for all patients with POI or early menopause unless they have contraindications.
Systemic MHT is the most effective treatment for vasa motor symptoms. It should be offered as a first-line treatment for symptomatic permenopausal and post-menopausal patients without contraindications or use hormonal contraception if that's more appropriate.
Non hormonal medications should be offered if there are contraindications to systemic MHT or if the patient prefers to avoid hormones.
I would caution you against using AI to answer any menopause related questions at this time. I don't think that it's worth the environmental impact based on how inaccurate the answer may be. There was a study last year that found that chat GPT was only 67% accurate, open evidence 60% and Gemini 47%.
If you or your patients want to follow some reliable accounts on social media, I'd recommend following one of these organizations. The Canadian Menopause Society, the Menopause Society, formerly known as the North American Menopause Society, which is an American organization, or the International Menopause Society.
Patients are able to self-reer for a menopause education class by phoning our clinic. And the class is done over Zoom, so they don't need to live in the Edmonton zone.
Currently at our clinic, we're prioritizing complex cases, and you can review the Alberta referral directory to get our most up-to-date referral criteria and a list of required information. A referral letter is adequate. If you still have any old referral forms from our clinic in your EMR, you can just get rid of those. You don't need to send a form along with the letter. If you have a patient who doesn't meet our referral criteria, you can ask for advice or refer them to a community women's health clinic. And there are a lot of hidden gems that are not that well known in terms of other clinics taking these kinds of referrals.
If you want to get advice, there are a couple ways that you can do it. So, we offer econults through NetCare and Althia. Or if you'd prefer to have a phone conversation in the Edmonton and North zones, you can call connect MD and speak to someone through the women's health specialty. Or in Calgary zone, you can use specialist link to speak to a gynecologist.
Please try out the pathway and submit feedback. We're going to meet again this summer to um go over all the feedback that we've received and make some changes to try to make it even more useful for you. I would also recommend joining the Canadian Menopause Society if this is an area that interests you.
They put on excellent conferences and webinars and they also have a private Facebook group that you can join to ask for advice from colleagues.
And these are my references.
And now I'll take some questions.
>> Oh, awesome, Alexander. Thanks a million. We have so many questions. So, folks, please have a look and upvote those ones that you really, really want to make sure get to. Uh, Janev has a question around whether or not um she has a patient with a personal history of breast cancer and whether they could be prescribed MHT. Uh, what if she's tried non hormonal therapies with no relief and tells you she'd rather have cancer than suffer the vasom motor symptoms?
Yeah. So that would be a case where, you know, I would at least want to make sure she's had a good trial of one of the best non hormonal medications. So I was would suggest having her try something like phases for at least 2 to 3 months.
And if that's really not giving her the results that she wants to see, then she could make an informed decision to go on MHT. Uh, I would that would be a situation though where I would recommend using the lowest dose necessary and for the shortest period of time and potentially reaching out to a specialist to figure out what some of the lowest risk options might be for her. But I do have a handful of patients who have chosen to go on systemic MHT because they felt like it made a really big difference to their quality of life.
>> Okay, awesome. Uh and um JC was asking about uh whether you could comment on testosterone used in patients with lowered libido uh both in pmenopause and menopause because it seems something that patients are interested in. You might have covered that a bit.
>> Yeah, I kind of covered a little bit.
Um, that being said, one thing I I'll add. You know, I did mention in the slide that, you know, it's used for post-menopausal women, and that's just because there's not currently enough research in permenopausal women to know if testosterone therapy is helpful for them. Um, if you look at appropriately selected patients, meaning that you've um ruled out other issues like relationship factors or vaginal dryness or other things that could be contributing. Overall, there's about a 50 to 60% response rate in in terms of who's actually going to improve with testosterone therapy. The remainder of people are really not going to have much improvement with it. Um, generally I'll do, you know, about a six-month trial of it, and if it's not helping within 6 months, it's not usually worth continuing it. Um, but yeah, that could be its own huge topic. So, I I think I'll leave that question there.
>> We might need to bring you back, Alexander.
>> Yeah. Sadia is saying uh she has a patient 54 year old post-menopausal with fibroids indometriosis history adenomiosis and chronic headaches and hot flashes uh was tried on my fem and prometrium of the last few months with relief of symptoms but severe aggravation of the headaches. So wondering what might be thoughts there.
Yeah, that can be challenging. You know, for people who are prone to getting headaches, some are going to be more sensitive to hormones than others. My approach is usually to just start with a really, really low dose. So, if you look at something like by Juva, for example, that one um would be considered more of a moderate dose. So, I would maybe pick something where you can start at a much lower dose. And that Canadian Menopause Society dosing equivalency table would give you some options there. I would just start at the very lowest dose. give them a few months to get accustomed to that and kind of gradually increase the estrogen from there and and try to find a dose that hopefully helps with their symptoms without worsening their headaches. Um, you know, and if you really can't find anything that seems to be the right dose, then maybe a non hormonal medication might be a better fit.
>> Okay. Um and the next question was uh um from Chidbear uh whether it's common practice uh here to have women on IUD within 5 years of insertion also be on oral progesterone uh with estrogen. Um so why is they're commenting that they've noticed that this is happening um like marina plus 100 milligrams of oral progesterone plus estrogen. So yeah, why would that happen? Thoughts on that?
>> Yeah, good question. That's something that I'm certainly seeing a lot. Um, there seems to be this idea out there that more progesterone is going to be better. Um, I do have a handful of patients who have a Marina that's still new enough to be active. Um, where they I might still actually have them on a tiny bit of oral progesterone. And that would just be because there are some patients who do get significant sleep benefits from progesterone. So, they truly feel better on it. But for a lot of women, progesterone is actually pretty neutral for their sleep. It doesn't make a big difference. It can even give them more vivid dreams or make them feel too groggy in the morning. Um, and a lot of women also actually get negative mood symptoms with progesterone. Um, and so my answer would be that, you know, it might be appropriate for some patients, but I am seeing that some clinics, especially the private clinics, just seem to be prescribing as much progesterone as possible. And if it doesn't seem to be working, just adding on more and more and more. And I don't agree with that approach at all. I think that, you know, can be pretty harmful. But in in appropriately selected patients, sometimes it makes sense to have a bit of oral progesterone if they're truly finding it helpful for their symptoms.
Awesome. Hey, Nathan. Nathan has a a patient who's come in recently from a private clinic with compounded topical progesterone for PRN use who um the patient feels it's helpful. I'm wondering if there's any evidence for that at all. Yeah, good question. So, progesterone is really not absorbed well through the skin. Um, just a quick aside to that would be that a lot of synthetic progesterines are still absorbed well.
So, if you look at some of the combination patches that have a progesterine in those, those ones are fine. But progesterone itself, which is what's in these compounded creams, doesn't actually get absorbed all that well. And so, it's likely a placebo effect, but who knows? It hasn't really been studied well.
>> Okay. Um Emily is asking uh whether migraine with neurological symptoms is still a contraindication to estrogen therapy.
Yeah. So in general it would not be a contra indication but it would be a reason to choose transdermal estrogen.
And if there is any question that you know that someone may have had a TIA or a stroke or anything more unusual than that then I'd recommend checking in with a neurologist first. Um, but many patients who've had migraines with neurological symptoms can still take transermal estrogen.
>> Awesome. And Emily is giving you a shout out for great talk. Thanks, Emily. Okay.
Um, Haley is wondering, um, yeah, I think Haley, the biioidentical stuff was covered in the and everyone will, by the way, receive a copy of the recording plus the pearls which summarizes the key elements of the slides because that's coming up a lot in the questions. Um, Miriam's asking, uh, is oral progesterone required with use of combined patches for menopausal symptoms? So, if they have the combined patch, do you need extra progesterone?
>> No, that's a good question. If it's Yeah. any of those standard MHT combined patches, there's no need to add um any additional progesterone on top of that.
>> Okay. And Kenneth Sax's asking, "What do you how do you respond to a patient who's adamant about hormone testing?
Should we give in at some point?
>> That one's hard, but what I often tell people is, you know, that often the answers are the results are so misleading. I've seen so many patients who before they were referred to me, they had some hormone level testing done and it came back looking as if they were premenopausal and yet they were having a lot of menopause symptoms, but they were told, "Well, no, your symptoms can't be related to menopause because look, your hormone levels were normal." And you know, that creates so many issues. And then even, you know, sometimes patients once they're on hormone therapy. They want to then get their hormone levels tested, but there isn't really a target hormone level that we need to be aiming for, we treat based on, you know, addressing symptoms without hopefully causing side effects. And we don't even know, you know, if the same hormone level in someone's bloodstream is, you know, if it if that's going to be right for someone and wrong for someone else, cuz the level in your blood doesn't really tell you everything about how it's actually acting on your cells. Um, and you know, proteins in the blood like albammen and sex hormone binding globbulin can all have an impact as well on the activity of these hormones. So, there's really not any level that we need to be aiming for. Okay. And then I'm just going to put a little plug in here. We do have a course coming up folks on how to help your patients living with obesity. Uh, Leslie has a question here around um the dosage increase in progesterone. Why does that need to happen with GLP1s?
Yeah. So, it's thought that there's just a delay in the absorption of oral progesterone and so um just as a precaution, it is recommended to increase that dose at least for that period of time. Um and I know there have been concerns with some of the GLP-1 medications also interfering with the effectiveness of birth control pills.
So, it's just a similar idea where at least initially um absorption is just a bit too slow. And great caution in folks with gabapentin in those folks uh because it's really obesogenic. Uh Leanie wants to know what dose of TRT you prescribe.
Yeah. So the recommended dose of testosterone is going to be onetenth of the male dose um because we don't have any female products specifically in Canada. You're going to use one of the male medications. Usually the one that I go with is Androgel because it's more likely to be covered. And so that one comes in a bottle um where you can pump out the dose. So I would start with one pump twice a week. Um and if levels don't go too high with that I might increase to one pump three times a week.
Alternatively you can get Testum which comes in little pouches. And for a man one pouch would be the daily dose. So you can do one/tenth of a pouch for a woman. Um and to help to learn the dose I recommend putting it in a syringe initially and then um just measuring out. So it would fill a 5 mm milll syringe. Use 0.5 milliliters per day.
But eventually once someone gets used to it, it is okay for them to then just eyeball the dose as long as those pouches are lasting 10 days.
Wow, Alexandra. Well, we ran over by 2 minutes. Um, but so many great questions and so many people weighing in. Thank you. Thank you. You know, really valued um all your presentation.
Um, so gosh, thank you so much on behalf of everybody for just this tour to force and uh, yeah, anytime you want to come back and do more, please feel free. Um, so folks, thanks so much for coming and for all the great questions. We will be sending out that pearls for practice.
Um, and uh, yeah, and I think Natassia in the background will take note of the couple questions that might be there.
Make sure we highlight those on the pearls for practice.
>> Thanks, Alexandra.
>> Thank you.
>> And thanks everybody in the background.
Yeah, you've got you've got like everybody going thank you, thank you, thank you, thank you. I hope you're taking advantage of the chat. Like this has just been such a huge contribution, Alexandra. Really, really appreciate you.
>> Yeah, happy.
>> All right, folks. So, we'll see you at the next with the next of with
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