Managing a Healthy Menopause with Dr. Fiona McCulloch: Rational Wellness Podcast 306

Dr. Fiona McCulloch discusses Managing a Healthy Menopause at the Functional Medicine Discussion Group meeting on April 27, 2023 with moderator Dr. Ben Weitz.

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Podcast Highlights

5:35  Perimenopause usually starts around age 39 till 55 or so and this is when we start seeing irregular cycles and lots of symptoms and increases in chronic health risks.  Perimenopause is a time of fluctuation.  Women are born with all of the follicles in their ovaries for their entire life. the follicles house the eggs and each egg is housed by cells that make hormones.  Over the lifespan the pool of follicles decrease and when you get to the end of the reproductive years, there are far fewer follicles and hormones are released abnormally and inconsistently.  During a normal menstrual cycle the granulosis cells in the inner follicle make estrogen and when the egg comes out, it ovulated and the shell of the egg makes progesterone for two weeks.  During perimenopause we have follicles on their last legs and they make estrogen all the time but not in a normal pattern and there is almost no progesterone.  The adrenals do make small amounts of progesterone but the ovaries make massive amounts of progesterone.  Perimenopause is marked by wildly fluctuating wild estrogen levels up and down and pretty much no progesterone for the majority of the time.

10:37  Diagnosis of Perimenopause. The pituitary gland is involved with the complex control of ovulation.  When estrogen levels start to drop, the pituitary senses that and then sends FSH down to the ovary to make an egg and then you get increased estrogen.  When estrogen levels get irregular but generally higher, the brain will stop making FSH, so some measure FSH as a way to diagnose perimenopause. But FSH is not consistently low, so it is not a good way to diagnose perimenopause. The best way to diagnose perimenopause is not to test hormones but based on age and that the menstrual cycle gets shorter, irregular. Women will get insomnia, have mood changes, etc.  Testing can be useful for treatment but not for diagnosis.  Menopause is easy to diagnose, since it is diagnosed when it has been 12 months since the last period. 

14:32  Stages of Perimenopause.  During the first stage of perimenopause, the cycles become shorter because there are less follicles and they make less anti-müllerian hormone, which slows them down from ovulating too early.  In the later stages of perimenopause we see highly unpredictable cycles and lots of heavy, long bleeding. Some of the common symptoms that may occur in menopause include hot flashes, insomnia, anxiety, depression, low libido, vaginal dryness, autoimmunity, insulin resistance, loss of bone density, increased cardiovascular risk, and increased Alzheimer’s risk.   

20:12  Hormone testing.  Different modalities of testing are more or less effective for different reasons. Serum or blood spot is the most common form of hormones testing and it is good at picking up topical estrogen, oral and vaginal hormones.  Topical progesterone is not seen very well in a serum test, but it is seen in a blood spot or in saliva testing.  Urine testing is good to look at the metabolites of estrogen and cortisol and Dr. McCulloch will typically use DUTCH testing.  But urine testing is not as good to monitor topical hormone replacement therapy or vaginal HRT, since this can end up in the urine directly.  Saliva is helpful to look at the diurnal rhythm of free cortisol and is good for picking up topical progesterone.  For saliva and blood spot testing she will use ZRT Labs.

24:28  Other labs that Dr. McCulloch will often order besides hormones include the following: 1. Lipids, 2. ApoB, 3. Homocysteine, 4. HOMA-IR, 5. HBA1C, 6. Glucose, 7. OGTT with insulin, 8. Liver: AST, ALT, GGT, 9. CBC, 10. Ferritin, 11. Iron panel, 12. Thyroid, 13. Cortisol, 14. AMH may be useful in differentiating irregular cycles from PCOS, 15. FSH and LH.

28:33  Diet.  Dr. McCulloch often recommends a low glycemic Mediterranean diet with lots of cruciferous vegetables that helps with estrogen metabolism and preventing breast cancer. They also contain antioxidants like sulforaphane that helps with CVD, insulin resistance, cellular overgrowth, and cancer prevention. Lignans and flax seeds and sesame seeds can mimic estrogen and have other benefits. Women should avoid processed foods, alcohol, and high glycemic carbs.  Calcium, magnesium, vitamin K2, and boron can help to prevent osteoporosis. 

29:51  Dr. McCulloch feels that soy is healthy as along as it is organic and non-GMO and the person is not sensitive to it. 

30:25  The Women’s Health Initiative study, which was first published in 2002, Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal WomenPrincipal Results From the Women’s Health Initiative Randomized Controlled Trial.  When this study was published it pretty much scared all women and doctors from using Hormone Replacement Therapy because it increased the risk of heart attacks, blood clots, and cancer.  One of the problems with this study is that they used oral, conjugated equine estrogen and synthetic progestins.   Another problem is that the average age that these women started to take it the hormones was 63 years of age.  Another issue is that 50% were current and past smokers, 35% with hypertension, 70% were obese, and there was no control for atherosclerosis.  And the group of women who took this dangerous kind of estrogen–the conjugated equine estrogen–without the synthetic progestins had no increased risk.  It’s the synthetic progestins that really increase the clot risk and these are in birth control pills, Provera and Depo-provera. They are orders stronger than natural progesterone and they don’t act like progesterone anyway. We are not sure why initiating hormones 10 years after menopause, but it may be because such women will tend to develop plaques once the estrogen drops and then when they start taking hormones, estrogen may soften some of these plaques and increase the risk of an event.

33:12  What we know now from research is the following:

1. Topical estrogens (patches, gels, creams) are safer than oral estrogen. We have known for years that oral estrogens cause blood clots. 

2. Topical estrogen and progesterone (even synthetic progestins) do not increase breast cancer risk up till 5 years after the last menstrual period.

3. While synthetic progestins increase the risk of clotting, this does not occur with micronized bioidentical progesterone.

4. While starting hormones more than 10 years after menopause may increase the risk of cardiovascular disease (CVD), especially in those who are obese, smokers, or have high blood pressure, initiating topical estrogen and natural progesterone within the first 10 years after menopause  is protective against CVD.

41:33  Topical estrogen. Many doctors recommend a compounded form of topical estrogen called Biest that includes both estrodial and estriol, with the thought that estriol is a weaker but safer form of estrogen.   The trend used to be to recommend 80/20 with 80% being estriol, but then you have to give higher dosages to control symptoms, so 50/50 Biest is best.  Dr. McCulloch will titrate the dosage to the amount of estradiol being absorbed, since that is the estrogen that modulates the symptoms, while estriol is essentially there to possibly mitigate risk.

43:15  Vaginal hormones.  For women who may be at increased risk for breast cancer or who are afraid of that possible risk, but who would like to improve vaginal dryness and atrophy, is it best to use vaginal estrogen or can vaginal DHEA work as well or even vaginal testosterone?  Vaginal DHEA has been shown to work really well. In the US, the Bezwecken DHEA Cubes work really well and these are over the counter, though they are not available in Canada. The other option is to use vaginal estriol plus hyaluranic acid, which also retains water and helps to lubricate the vagina. 

45:50  The clinical differences between estrogen and progesterone. 


Benefits of bioidentical estrodial: 

1. Very effective at reducing hot flashes, while progesterone can help with hot flashes, but not that much.

2. Estrogen has the most effect on vaginal dryness and atrophy.  If vaginal estriol with hyaluranic acid or DHEA don’t work, low dose estradiol vaginally works amazingly.

3. Improves bone density.

4. Promotes better mood/less depression.

5. Libido is primarily driven by estrogen and not by testosterone, as is commonly thought. 

6. Cognition.

Over replacement.

Taking too much estrogen or having too much estrogen because the ovaries are still putting out some can result in breast tenderness, mood swings, sadness, crying, irritability, acne, spotting, bleeding, weight gain around the waist and hips.  Using Canadian units at the beginning of the cycle, the estrogen’s about 100 and at ovulation it’s about 800.  In the Luteal phase, it’s about 400.  When we use topical bioidentical estradiol we are putting women’s estrogen somewhere around 150-250.  But if they are in perimenopause, sometimes their ovaries will bust out an egg and estrogen levels might surge to 1500, which will cause overreplacement symptoms.


Benefits of Bioidentical Progesterone: 

1. It opposes estrogen and it thins the lining of the uterus and prevents endometrial cancer. You don’t need to use progesterone if they don’t have a uterus.

2. Menorrhagia. Progesterone is amazing at reducing heavy menstrual bleeding. 

3. Sleep. It improves the depth of sleep, though it doesn’t help with the hot flashes that can wake women up as much as estrogen does. Progesterone turns into allopregnanolone, which crosses the blood brain barrier and it improves calmness, stimulates GABA production, and promotes sleep. This is also why oral progesterone should be given at night.

4. It also improves bone formation.

5. It improves cardiovascular disease and promotes the health of the arterial endothelium. It is anti-inflammatory and reduces coronary artery disease.  

Over replacement.

Too much bioidentical progesterone can make women feel groggy, drowsy and retain water. 


52:58  Synthetic Progestins, like MedroxyProgesterone, Norgestrel, and Norethindrone, are not Bioidentical Progesterone.  Synthetic progestins all behave differently but some can cause clotting and proliferation of breast tissue, while bioidentical progesterone does not cause these.

53:52  Androgens.  Menopausal women may have a relative increase in androgens because while androgens will slowly decline with age, estrogen and progesterone levels will drop drastically.  Thus the androgens tend to become more dominant and they can cause hair loss on the head and hair growth in other areas and exacerbate symptoms for patients with PCOS.  Progesterone is actually anti-DHT, so it is an anti-androgen. It can lower LH, so this will tend to lower androgens.  There are also some herbs like saw palmetto that can help.  On the other hand, some patients can benefit from taking testosterone or DHEA, esp. if their levels are really low.

55:41  Herbs.  The first category of herbs are the Endocrine Adaptogens.  These herbs help the endocrine system to adapt to change. Some herbs are androgenic herbs, including maca, tribulus, Panax ginseng, damiana, epimedium, bacopa and Gotu kola.  These herbs tend to help with low libido, fatigue, and energy and they tend to stimulate testosterone. There are other herbs that are estrogen and progesterone types of herbs, including Shativari, black cohosh, wild yam, siberian rhubarb, red clover, Vitex agnus castus, kudzu, Dong quai, and hops. Shativari is an Ayurvedic herb that is helpful during perimenopause for mood, skin, hair, hot flashes, and for energy. Black cohosh is famous for both perimenopause and menopause. It used to be thought of as being a phytoestrogen, but now we believe it works in the brain. We often think of wild yam as mimicking progesterone, but it has to be converted into progesterone in a lab, so just taking the ground herb will not convert and it actually has more estrogenic effects in the body.  Siberian rhubarb, Estrovera from Metagenics, is the top recommendation for hot flashes besides taking estrogen.  Red clover is another phystoestrogen.  Vitex is often thought to be progesteronic, but it is not, though it can encourage ovulation in certain situations, which increases progesterone. Vitex actually acts on dopamine and prolactin in the brain. Vitex can be especially helpful if the patient has amenorrhea and stress, which is usually related to high prolactin. Kudzu is another phytoestrogen that is quite strong and can also help with hot flashes. Hops is also a phytoestrogen. Dong quai is from traditional Chinese medicine and it is a tonic that is similar to shatavari.

1:01:00  Adrenal Adaptogenic Herbs.  Adrenal adaptogenic herbs include Ashwaganda, (Withania somnifera), Holy basil, Eleutherococcus, Rhodiola, Panax ginseng, and sage.  Ashwaganda is a good herb to be given in the daytime for anxiety and irritability. It is also a very calming herb that can be given at bedtime to keep people from waking at night from a cortisol spike.  Holy basil is a good mood booster in perimenopause and it also has nice effects on skin and hair.  Eleutherococcus is an adaptogen that helps to manage stress and it helps energize patients. Rhodiola is a very uplifting herb that can help with low cortisol or depression or fatigue, dopamine problems.  It can also help with attention, brain fog. Panax ginseng actually is quite similar as it is an uplifting, stimulating herb.  Sage is really good for mood, energy, and overall cortisol balance.

1:02:55  Sleep and Mood. Supplements that can help with sleep in perimenopausal and menopausal patients include magnesium, melatonin, valerian, skull cap, passionflower, Zizyphus, and ashwaganda.  Dr. McCulloch likes the Ayur-Ashwaganda from Douglas labs 2 caps before bed is really helpful for preventing the 3:00 AM wake up.  For mood, esp. for anxiety and irritability, GABA, threonine, phosphatidylserine, taurine, Ashwaganda, St. John’s wort, and Vitex can all be very helpful.  It should be pointed out that you can’t combine St. John’s wort with SSRIs.


Dr. Fiona McCulloch is a board certified Naturopathic Doctor and founder of White Lotus Integrative Medicine in Toronto Canada, serving thousands of women with hormonal conditions since 2001. Dr. Fiona’s best selling book 8 Steps To Reverse Your PCOS, offers well-researched methods for the natural treatment of Polycystic Ovary Syndrome. Fiona is also a medical advisor to and developed the nutrition methodology for the OpenSourceHealth PCOS project which analyzes molecular, genetic, metabolic and hormonal markers in women with PCOS. As a woman with PCOS herself, Dr. Fiona feels fortunate to serve as a guide, providing trusted information that empowers women to manage their own health.  Her website is DrFionaND.com.

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.



Podcast Transcript

Dr. Weitz:                            Okay. Hello, everybody. I’m Dr. Ben Weitz and welcome to the Functional Medicine Discussion Group Meeting tonight. We’ll be discussing the health challenges and successful strategies and treatments that functional medicine practitioners like us can employ to help women with women’s health expert, Dr. Fiona McCulloch. I want this meeting to be interactive, so please participate by typing your questions into the chat box, and then I’ll either call on you or ask Dr. McCulloch your question when it’s appropriate. May 25th, we have Dr. Mark Pimentel and we’ll be discussing SIBO and IBS. I’m working on June 22nd. I’m thinking about possibly doing one in person. Details still to come on that, probably on adrenal.

                                                July 27th, we have Dr. Dale Bredesen on Alzheimer’s disease. If you’re not aware, we have a closed Facebook page, which is for practitioners only, the Functional Medicine Discussion Group of Santa Monica that you should join so we can continue the conversation when the evening’s over. I’m recording this event and I’ll include it in my weekly Rational Wellness Podcast, which you can subscribe to on Apple Podcast, Spotify, or YouTube. If you enjoy listening to the Rational Wellness Podcast on Apple Podcasts or Spotify, please give me a five-star ratings and review. The latest podcast is an awesome interview with Jeffrey Smith on the dangers of GMO foods and glyphosate and it’ll really blow your mind, so you got to listen to that one. That’s out now.

                                                I want to thank our sponsor for this evening, Integrative Therapeutics. Usually, Steve Snyder’s able to join us, but he’s not able to. He’s attending a naturopathic conference, so I want to tell you about a few Integrative products. Integrative offers several products that help with estrogen metabolism, including Indolplex, which is an enhanced absorption form of DIM. They also have a very good formulation of calcium D-glucarate. They also have a very good quality and reasonably priced Vitex Extract. Finally, Integrative now has an even more advanced form of curcumin with even greater absorption than their Theracurmin, which is currently my favorite form of curcumin. This new product is called Curalieve, and it is an amorphous, solid dispersion of curcumin.   Apparently, curcumin forms crystals, and that’s one of the reasons why it’s difficult to get absorbed. So, this is a solid, amorphous form. I’m not even sure what that is and apparently has way higher absorption rates.

Dr. Fiona McCulloch is a naturopathic doctor and founder of White Lotus Integrative Medicine in Toronto, Canada, serving thousands of women with hormonal conditions since 2001. Dr. Fiona’s best-selling book, Eight Steps to Reverse Your PCOS, offers well-researched methods for the natural treatment of polycystic ovary syndrome.  I’ve referred to that book a lot when dealing with patients with PCOS. It’s really an awesome book. Dr. Fiona is also a medical advisor too and developed a nutritional methodology for the Open Source Health PCOS Project, which is a women’s health technology platform. All the way from Canada, Dr. Fiona McCulloch.  Thank you so much for joining us.

Dr. McCulloch:                   Thanks so much for having me. I always love being on your podcast and presenting. Of course, I love everything about hormones, so I’m really excited to present on this topic.

Dr. Weitz:                          That’s great.

Dr. McCulloch:                   Yeah, so I’m just going to start off talking about perimenopause and menopause. I always find it very hopeful to differentiate between these two, because they’re actually quite different and they need different support, but they both cause lots of different issues. Sometimes perimenopause is actually worse and is often missed altogether. So, yeah, I am Dr. Fiona McCulloch. I’ve been practicing in the area of hormonal health for 22 years in Toronto. I’m a naturopathic doctor and I’m a board member of the Endocrinology Association of Naturopathic Doctors. So, I’ve prescribed lots of hormones. The majority of my practice is polycystic ovary syndrome, menopause, thyroid, adrenals. So, yeah, I really love this topic.

                                                So, first, I just want to talk about the different stages that we see in the lifespan in women. So, the first stage is premenopausal. This is when patients are having regular cycles. It’s generally from the time they have their first period up until usually around 40 or so. Some people have this a little earlier, but for the most part, it’s around this age that we see perimenopause happening. So, around age 39 to 55 is usually perimenopause. We start seeing irregular cycles, changes in cycles, and that’s when lots of symptoms begin as well. Menopause is defined as 12 months past the last menstrual period, and this is where we see a lot of the chronic health risks rising. So, they’re both very important times. They have different sets of problems to deal with.

                                                So, the first thing to know is that perimenopause is a time of fluctuation. So, its very nature is change. It is very chaotic hormonally. I’ll show you what goes on there and why it is so challenging. A lot of the time patients will come in unaware that their symptoms are from perimenopause, because they’re still having periods. A lot of patients believe that until they actually stop having periods that it can’t be related. So, this is something that can be missed a lot of the time. A lot of these patients are diagnosed with anxiety, depression, and things like that. Meanwhile, they’re actually in perimenopause. So, it’s really important to be able to figure out if that’s what’s going on here. So, what is it that causes that to happen hormonally?

                                                So the first thing is that women are born with all of the follicles in their ovaries for their entire life, and the follicles basically house eggs. So, each egg is housed by different cells that make hormones, and these follicles basically are ovulated. There’s an ovulation that occurs every month from one of the follicles. Over the lifespan, the pool of follicles decreases. As you get to the end of the reproductive years, there are far less follicles. When that happens, we start seeing some irregularities. These follicles don’t behave normally. There’s less of them. They release hormones abnormally, and many times they don’t ovulate. So, these are basically the end of the road of the ovulation process, and we’re seeing a lot of inconsistent hormone production as a result of that.

                                                So, if we look at what actually happens on the left side in a reproductive cycle, on the left, this is a normal healthy menstrual cycle where we’re seeing the very beginning of the cycle. A lot of people are not that aware that the estrogen is actually made from the follicle during the process of ovulation. So, at the very beginning of the cycle, over on the left side here, there are these very tiny follicles and they’re not really active. They’re sitting there quite mostly dormant, and the brain will then start to grow a follicle to get ready for ovulation. The inner part of this follicle makes estrogen. That’s called the granulosis cells, and the outer part actually makes estrogen and the estrogen actually will spike up quite high as the follicle enlarges.   So, it makes a lot of estrogen that stimulates the process of ovulation. The egg comes out, it’s ovulated, and then the shell of the egg makes progesterone for two weeks. This is where the vast majority of our progesterone comes from. If you look at the beginning of the cycle there, see how there’s so little? That’s the amount that comes from your adrenal glands. It’s almost nothing compared to how much comes from the ovary. The ovary makes massive amounts of progesterone. The adrenal makes tiny amounts of progesterone. So, throughout the reproductive lifespan, we have large amounts of progesterone for two weeks, very little progesterone for two weeks, but then estrogen goes through this lovely pattern where it’s up and goes up in that pattern to ovulation and then another little bump around the gluteal phase.

                                                Perimenopause, what we see over here is that we have all these follicles. They’re not really functioning normally because they’re old. They’re on their last legs and they’re about to sputter out. So, basically, they just randomly make estrogen. They make estrogen all the time, but they don’t make it in a normal way. Sometimes they make a lot, sometimes they make none. It’s up and down and all over the place. Progesterone only happens when you ovulate. So, you have this little bit from the adrenals, but then that large amount is just not there most of the time. Only when ovulation occurs, two weeks of progesterone are made. That’s random in perimenopause and when it does happen, sometimes it’s way less than you would see. So, you’ve got all this estrogen, almost no progesterone, definitely not that normal half and half pattern that we’re used to having. So, that’s a huge change that we see in perimenopause. So, the two big things are really fluctuating wild estrogen levels up and down and pretty much no progesterone for the majority of the time. We do get some sometimes, but unpredictable.

So, let’s talk about why these wild fluctuations happen in the first place. If we look at what the pituitary gland does, the pituitary gland is involved in very complex control of ovulation.  Whenever your estrogen levels are very low, the brain sees that and says, “Oh, we need to make an egg. Let’s grow an egg.”   It basically sends FSH right down to the ovary, starts to grow the egg, and that’s what makes the estrogen. So, basically the stimulus to grow an egg is low estrogen. Whenever estrogen’s low, the brain’s like, “Push an egg.” So as you can imagine, that drop will make the brain push out an egg. Then we get a big burst, and then maybe that exporters out drops. So, now we get this back and forth, up and down between the brain and the ovaries. So, once the estrogen goes up to the brain, then it stops making FSH. So, sometimes the FSH will be low, sometimes it will be high depending on what’s happening at the time. So, it’s quite random. This shows you what happens when there’s high estrogen. So, high estrogen, the pituitary gland will shut down FSH.  Basically, we don’t need to make an egg. We already have one. The times that that occurs are really right around ovulation. We wouldn’t be growing an egg at that time because we’re already ovulating. We wouldn’t be doing that in the luteal phase, second part of the cycle, it’s already lots of estrogen. So, at those times, we don’t want to grow an egg and that’s totally normal. If someone is pregnant, also, high estrogen, don’t need to grow an egg. In perimenopause though, it’s high randomly all the time. So, basically it’s up, the brain is like, “No FSH,” then it’s down, and then the brain’s like, “Yes, FSH.” So it’s basically up, down, all because of these eggs that are really burning out and not able to do their normal function of ovulation.  So, this is basically this back and forth process, up and down estrogen. Basically, it’s a very bumpy ride. It’s very unpredictable. The reason I’m showing you that is sometimes people test FSH to diagnose perimenopause. That often can be very misleading, because sometimes it’s high, sometimes it’s normal, sometimes it’s low. It’s just all over the place. It’s totally random. So, it’s something to consider, but I certainly wouldn’t say, “Oh, that person has normal FSH, they’re not in perimenopause.” So these are really important things just to understand diagnostically. So, yeah, perimenopause, we see this up, down of these hormones, very random, up and down of FSH, up and down of estrogen.

                                                So, how do we actually diagnose perimenopause given that we can’t actually test these hormones and know if that’s the cause? Really, it’s very easy to tell. So, you use clinical case taking basically if a patient is between 40 and 55 years old and they’re really having persistent changes to their menstrual cycle. So, they’ve always had a 28-day cycle. Now they’ve got a 25-day cycle. Now it’s a 24-day cycle. They have insomnia, they feel different, they feel weird, they’re having mood changes. This is perimenopause. That’s really all you need to know. There’s no test that will tell you more than that. It’s the age range and these symptoms and these changes to the cycle. Menopause is very easy as well. It’s 12 months since the last period.  But in menopause, we do have a very consistent testing to look at. So, the FSH knowledge are extremely high, usually over 30 for FSH.  Estrogen, progesterone will be very, very low. So, yeah, in menopause, you can use these tests. However, it’s also very obvious because the person’s not having periods. So, testing is useful for treatment, but not for diagnosis, because you can diagnose it just by talking to somebody and figuring out what’s happening.

The next thing is that there are different stages of perimenopause to know about, and the first stage can be a little bit subtle. What usually happens is the cycles become a little closer together. So, if somebody had a 28-day cycle, now it’s 25, 24, 23 days, that often goes on for a few years before the next stage of perimenopause.  This whole thing can last around 10 years, but the first stage can be quite long actually, where those cycles are shorter. Then ovulation is occurring early in that first stage. The reason for that is when there’s less follicles, they make less of a hormone called anti-müllerian hormone, which is basically something that slows them down from ovulating too early. So, you just start ovulating earlier and earlier and there’s just less regulation inside the ovary. It just starts pumping out eggs that are maybe working sometimes, maybe not at other times. We also in the later stages, start seeing highly unpredictable cycles. So, the cycles might be months apart. They might be two in a month. They might be bleeding for three weeks straight.  It’s just so unpredictable and chaotic, but definitely, we see a lot of the heavy, heavy long bleeding in this stage and that can be very problematic. That’s where a lot of patients in the old days would be given a hysterectomy, second stage of perimenopause, because unfortunately, they didn’t have treatments for that which we have now. Sometimes it’s still done, but there’s so much more that can be done now. So, we don’t have to have a hysterectomy just because of this last stage of perimenopause. So, the symptoms in perimenopause, if we think about perimenopause as the left side of this graph where the right side is menopause, perimenopause still has estrogen. So, you’re not going to have constant estrogen deficiency symptoms.

                                                They’re going to be fluctuating, but you’re also going to have a bit of chaos and mayhem in how people feel. They feel up and down, mood swings, insomnia. It comes and goes. We see lots of autoimmunity happening here, because the immune system has to respond all the time to these up and downs of hormones, especially estrogen really causes a lot of changes to the immune system. So, migraines, it’s almost like PMS times a million all the time. It’s just up and down, all over the place. So, yeah, a lot of patients come in this stage and they’re like, “I just feel really tired. I have anxiety, I have depression. Something is wrong.” Then nobody ever brings up that they might be in perimenopause. So, this is often misdiagnosis, something else in this stage.

                                                But just to keep an eye out for these imbalance symptoms where heavier periods, irregular cycles, mood changes, sleep changes, a general change in how people feel. It’s all very common. I am sorry, I don’t know why it has gone back there. One second. The menopause stages are really estrogen deficiency symptoms. So, this is where if we’re looking at that right side. There’s really no more estrogen. That’s where you really start seeing things like hot flash. I mean you can have them in the first stage, but in the second stage, the hot flash is really stark, because there’s no more estrogen, insomnia, anxiety, irritability, depression. But these symptoms tend to improve gradually, those top three a little bit as time goes on.

                                                They find in menopause, women, generally, their mood gets better if they’re given a little bit of time compared to perimenopause. But some of the symptoms and risks actually start accumulating from the lack of estrogen. So, that would be things like cognition, cardiovascular risk, insulin resistance, bone density. So, all of those things just continue and get worse over the years, and those are really caused by estrogen deficiency. We also sometimes see androgen excess symptoms like hair growth on the face, hair loss from the scalp. I’ll show you why that happens, because a lot of people are confused in that the testosterone’s actually quite low. So, why is this happening? There’s actually some reasons for that and everyone’s a little different. It depends on their predisposition there.

Dr. Weitz:                          Can I ask, do we understand why hot flashes occur from low estrogen?

Dr. McCulloch:                   So they don’t 100%, but some of the thinking or the newer information is suggesting that people who have high estrogen previously have more hot flash and they don’t 100% understand why that is.

Dr. Weitz:                          I mean, what is the body trying to do or compensate for?

Dr. McCulloch:                   They don’t actually know unfortunately. Yeah, it’s neurological in some way and there’s some pre-programming related to estrogen, but they haven’t been able to figure it out. It’s like a neurological circulatory element. Yeah, there isn’t really good answers on that unfortunately, because some people just have them like their whole life and it’s interesting. But I definitely see it in the patients that have high estrogen. Once they go through the final stages, they often have bad hot flash. It’s a different treatment process to go through those stages. The types of hormone testing that we can do. So, in perimenopause, although we cannot really diagnose it with testing, we certainly want to do testing to understand how we can help these patients because everyone’s a little bit different.  Everybody has different aggravating factors and I find that people’s predispositions are always worse in this phase. So, whatever they have already, it just gets worse.

So, there are different types of testing. I just want to briefly review them. There’s all different possibilities for tests. I mean some of them have pros and cons and it really depends. Sometimes it’s convenience. Sometimes it’s a combination of different tests that will make you choose between one or the other, but blood spot and serum testing is definitely probably the most common type of testing that’s done. It is really good at picking up endogenous hormones.  So, hormones that we make in the body naturally. It is also good at picking up topical estrogen, oral and vaginal hormones. We just have a lot of data on that and what those levels look like in serum. Topical progesterone is not seen very well in a serum test, but it is seen in a blood spot test, because it’s found in capillary blood more so. If you ever do progesterone cream and you run a blood test, you’re not going to see it much there at all. You’re going to see a tiny bit, but if you do capillary blood spot or saliva, you’ll see the progesterone cream.

Dr. Weitz:                          Wow, that’s an interesting pearl right there.

Dr. McCulloch:                   Yeah, it’s one of those things that they don’t actually know how it’s actually absorbed, but they believe might be lymphatic and that’s why it’s showing up that way. But nobody’s actually studied that properly to find out because they believe the progesterone cream isn’t absorbed. So, they won’t study it, but it is. You can pick it up in these tests. So, it is observed and I see that it is different. They’re just different forms. I think in the future, hopefully, that will be studied more so, but urinary metabolites are also very useful. Those show something a little bit different. So, those are going to pick up excretion and break down products of hormones. It can help us understand metabolites.

                                                So, if somebody has a risk of breast cancer, we can understand, “Do they make harmful metabolites of estrogen?” It’s not as good for a topical HRT assessment, because it is excretion and vaginal HRT, it can actually land in the urine. So, those are not really good. It’s not really a good way to assess how is the level in the person’s system, but it’s extremely helpful for adrenal issues because you can understand metabolites of cortisol, total cortisol free. You can do diurnal rhythm. So, it’s a great test for cortisol really, and saliva. So, saliva is interesting in that it’s very good at picking up topical progesterone. It can give you an instant measurement of adrenal free cortisol. It’s easy to do at home, so you can do diurnal. So, yeah, so that is basically saliva.

Dr. Weitz:                          For urinary, do you have a preference for dried urine versus 24-hour urine?

Dr. McCulloch:                   Yeah, I usually do dried urine. Yeah, I usually do that, but I have done 24-hour, just like if some patients don’t want to do the whole dried urine thing. I’ve done that, but I just find that’s good for just total cortisol.

Dr. Weitz:                          In Canada, do you have some of the same testing companies that we have here?

Dr. McCulloch:                   We do.

Dr. Weitz:                          You have the DUTCH testing. Okay.

Dr. McCulloch:                   Yeah, that’s what we use for, this is primarily the DUTCH test. We use ZRT also, but mostly the DUTCH test for the urinary metabolites.

Dr. Weitz:                          Okay. What about for saliva and bloodspot?

Dr. McCulloch:                   For saliva and bloodspot, I use ZRT. They have great tests actually. I really like ZRT. So, yeah, they have a lot. They’re adding more and more too. So, really good company.

Dr. Weitz:                          Cool.

Dr. McCulloch:                   Yeah. So, yeah, it really depends on what you want to know, which tests to do. There’s just many different reasons to choose each one. Lab panels, so these also would be selected for the patient and their risks. So, basically whatever you’re seeing here, don’t get too stuck on it. I see sometimes people doing the DUTCH test and they’re like, “Oh, you have no estrogen,” and then the person’s having periods not regularly, but they are. So, obviously, they have estrogen, but then it has to be understood that these hormones change all the time and that’s normal.  If it’s low, it’s low, but that tells you that sometimes it’s low. That’s all tells you. Other times, it might be high. If they’re having periods, they have estrogen. So, it’s really this understanding, you can look at it under, get a snapshot, but knowing that it changes is very important.

Dr. Weitz:                          Have you used the cycle testing where you test it every day of the month using DUTCH?

Dr. McCulloch:                   I have. I also have the fortune of working with a lot of fertility patients who go through cycle monitoring at fertility clinics. So, I get that, which is really cool, because then it’s repetitive. They’ll do a bunch of them, so I get to see that too. We do the cycle testing, so it just depends, but a single cycle’s really only a single cycle too. So, sometimes it just depends on what I’m trying to learn from that. Sometimes it is useful to figure out what’s going on. So, yeah, the estrogens, progesterone. So, the strong estrogen is estradiol. The other estrogens are estrone and estriol, and then there’s progesterone. So, all of these can be measured in blood spot and metabolites. The androgens can be measured.  I often do that in patients who have PCOS, because there’s a group of patients with PCOS whose androgens actually go up in perimenopause. Their DHEA shoots up through the roof and they get high testosterone and then they have all kinds of problems. They’ll lose all their hair or something like that very suddenly. So, those patients, I always test their androgens. Other patients, usually they’re going to be low, but there’s this category of PCOS patients where it goes up quite high actually, which is not fun for them, because they’ve gone through their whole time and now again, they have to deal with this problem. So, it’s good to make sure that’s what’s happening.

                                           The cardiovascular elements, I always test that, lipids, ApoB, CRP, homocysteine, insulin resistance, so HOMA-IR, A1C, glucose. Oral glucose tolerance test with insulin or even just fasting insulin can be really helpful. Liver enzymes to look for fatty liver, especially ALT, can be quite sensitive for that. Iron panels can be really helpful too in understanding fatty liver and then iron deficiencies in perimenopause are very common with the heavy periods and a full thyroid panel because a lot of people develop Hashimoto’s in this phase. Cortisol is really important. I really do like to do the diurnal cortisol whenever possible. Sometimes I’ll just screen it if the patient doesn’t want to pay for that test, but I’ll screen it with serum.

                                                Metabolites are really useful for someone with a complex condition. Other considerations, anti-müllerian hormones. So, sometimes say if a patient’s 36 years old, they’re too young for menopause, but they’ve had regular cycles, now of a sudden they’re irregular. If you want to find out, “Are they in perimenopause early?”, you can run AMH and that will tell you they have a very low egg reserve. They’re probably having those symptoms from perimenopause. FSH and LH, again, they’re high in menopause. In peri, they’re up and down all the time. Sometimes they look totally normal and sometimes they look really high, but they just move around. So, yeah, the labs are all very individual.

So, nutrition generally, of course like anything, a lot of different nutrition plans can work.  I don’t believe in any particular nutrition plan. I’m like, “What works for this patient that’s the healthiest way that they can eat according to their lifestyle?” But a Mediterranean low GI diet or an adaptation of that is often very helpful in this category for cardiovascular disease. Cruciferous vegetables, lots of those will help with estrogen metabolism, preventing breast cancer, but also antioxidants with sulforaphane, that really helps with cardiovascular disease, insulin resistance, cellular overgrowth and cancer prevention. Lignans and flax seeds, sesame seeds, they mimic estrogen.  They can have some really good benefits. CalMag mineral formulas are really critical. So, many patients will start to develop osteopenia as soon as their estrogen starts dropping. So, these are really important. Usually, they should have all the minerals and vitamins that go along with calcium and magnesium, like vitamin K2, boron. So, all of these micronutrients are really important.

Dr. Weitz:                          Steve asked about soy. What do you think about soy? Soy?

Dr. McCulloch:                   So soy, if it’s non-GMO and organic and the person doesn’t react negatively to it, is not sensitive, I’m actually fine with it. I think what the research shows is it’s beneficial. As long as it’s not GMO and not sprayed with tons of glyphosate. If it is, you don’t need it. Yeah, it’s sprayed with a lot of glyphosate, conventional soy. Still controversial though, right?

So the next thing I’m going to talk about is this study, the WHI 2002 study. Probably everybody remembers this study because they ring the alarm bells. They stopped this study. It was all over the news. HRT’s going to kill you, give you a heart attack and give you breast cancer and we need to stop it right away. I remember that very well. I remember being afraid of it and being shocked, because I had just graduated school at that time.  “Oh, wow, this is really dangerous” was my thought at the time. That thought has persisted. So, basically, it was the oral estrogen and synthetic progestins were reported to increase the risk of clot and cancer. However, what they said was HRT will give you heart disease and cancer. What we know now is that the statistical analysis and breakdown of that and the updated research has showed us that that was quite unfounded and also that there are very specific things to know about HRT that really are involved in that risk that we saw, but something to consider is that in that study, the average age was 63 years old. 70% of the patients were aged 60 to 79, 10% were aged 50 to 54.  It was using conjugated equine estrogen, which is synthetic oral estrogen, and synthetic progestin, which is oral hydroxyprogesterone. These are very different than what we use now. 50% were current and past smokers, 35% with hypertension, 70% were obese, and there was no control for atherosclerosis. So, so many flaws, just to say across the board. This causes heart disease. No, this is a very confounded study with lots of things that weren’t controlled for. So, even just looking at that alone tells us that needs more analysis. But if you want to go through this chart later, this is the breakdown of those studies and actually what the conclusion was.

                                                What you’ll see if you look through that is that really, even with these CEE estrogens, the most dangerous kind, there really isn’t an increase in the risk unless the progestin was added to it. So, that’s very important to know in that even the worst kind of estrogen did not have that risk in particular. Now, we just know so much more even that we would never use that estrogen now. So, I’ll show you the breakdown of what we know as a summary. So, this is just a summary of everything. All the research that we have now, topical estrogen, so transdermal patches, gels, creams, these are much safer than oral estrogen. The oral estrogen turns into metabolites in the liver that cause clot and thrombosis. We see that with birth control pills.  We’ve known that for many years that they cause clot and thrombosis. So, it’s really not a surprise that the oral estrogens cause that. Transdermal does not seem to cause this. So, this is really good news. Transdermal estrogen and progesterone together, and this is using a synthetic progestin because they haven’t got enough research yet, even on micronized progesterone, natural progesterone. But even that combination does not increase breast cancer risk up to five years past the last menstrual period. Synthetic progestins clearly increased clot risk. We’ve always known that. They’re in birth control pills, Provera, Depo-Provera. All these things we’ve already known, they increased clot risk. So, it’s absolutely no surprise that they do that in menopause and they’re very strong.

                                                Compared to natural progesterone, they’re like orders stronger. So, it’s not necessary to take something like that. Plus, it doesn’t act like progesterone anyway. But we don’t see that risk with micronized progesterone. They have not found any thrombotic risk with that. We do need more research to understand long-term safety, but so far, it really looks quite safe, which makes sense considering this exact form our body makes. Initiating HRT after age 60, so this would be not being on any HRT at all, going completely with no hormones for maybe 20 years. Sorry, not 20 years, maybe something like 10 years. The average age is about 50, 51.  If they were to initiate it 10 years later, there was an increase in cardiovascular disease, breast cancer in obese, smokers, and hypertensive people. Why is that? We don’t know 100%, but what we think is that those people have a lot of plaques on their arteries in particular. They just develop lots of plaques in that time and then the estrogen softens those plaques and that can cause a risk. So, for that group of people, it does seem to be a bad idea to start it after 10 years. That being said, we still need more evidence on that, but for those people, it’d be best for them not to wait. They might just be accumulating so much risk. Oh, I am sorry about that. I do not know why.

Dr. Weitz:                            So interesting. So, you’re saying in particular women who have calcified plaque might potentially be at more risk because the estrogen might make the plaque less stable.

Dr. McCulloch:                   Yes, it softens it. So, if they initiate it within 10 years, though we don’t see that risk. It’s only if it sets in for that time and it’s only in these risky groups. So, they already have a lot of plaque and then they’re probably rapidly getting a lot of plaque in that 10 years and then the estrogen softens it and may cause an event.

Dr. Weitz:                            So I wonder what you would think about a woman who’s suffering with the beginning stages of Alzheimer’s, let’s say she’s 65 or something and has not been on hormones and now we think that perhaps going on hormones might be beneficial. I guess you have to weigh both factors.

Dr. McCulloch:                   You’d have to weigh it. What I expect to see is that we will learn how to do that. There’s probably a way to initiate it or a dose to initiate with in people with cognitive, but it’s hard to know. If they don’t have those other risks, maybe it will be fine for them. It’s just like for the safety data, it’s going to take time to get that. Yeah, I personally think for cognition, it’s going to be continued quite a long time once we get the data on that.

Dr. Weitz:                            Yeah.

Dr. McCulloch:                   Yeah, initiation within 10 years of the last menstrual period is protective against cardiovascular disease. So, it actually reduces the risk of cardiovascular disease across the board. So, it’s a great idea to go on anytime within that 10 years. That’s quite a long time. Obviously, if you can go on it immediately, that’s great, but you don’t have to. So, lots of protective effects there. In patients with a uterus, it’s very important that whenever there is estrogen, there absolutely must be progesterone added as well. It has to be oral or vaginal, because transdermal progesterone is not strong enough to consistently deal with the lining and reduce the risk of endometrial cancer.   So, it has to be something like oral micronized progesterone or vaginal progesterone. I tend to use vaginal progesterone in patients with extreme heavy bleeding in perimenopause because it works really well. Outside of that, I would use oral micronized progesterone just because it’s great for sleep.

Dr. Weitz:                            Do you cycle the progesterone two weeks and in two weeks now, or do you have women take it every day of the month?

Dr. McCulloch:                   So I always cycle it in reproductive age women. In perimenopause, if their cycles are highly irregular, I find cycling it actually causes more bleeding problems off and on. So, I just tend to do it continuously, especially if they have heavy bleeding. In menopause, once they’re past full that full year, unless the progesterone’s helping them, you can do it 12 days a month. If they feel good on it though, you can do it every day. If they’re like, “I sleep better on the progesterone,” they can do it every day, but a minimum of 12 days, we’ll deal with the lining risk.

Dr. Weitz:                            Steve is asking, “Do you use ultrasound to check uterine lining thickness if on progesterone?”

Dr. McCulloch:                   Yes. So, I do. Because I deal with a lot of patients with PCOS, I have a lot of patients who’ve had endometrial hyperplasia and cancer in my practice. In perimenopause, most of the time that there’s bleeding, it’s not endometrial hyperplasia, but if a woman is past menopause and you see a bleeding, that is not normal. So, definitely do an ultrasound. I always do a baseline ultrasound anyway, just to have a good look and make sure nothing else is going on, especially if they have just dysfunctional bleeding. But I find in perimenopause, once they’re on really consistent past three months, you don’t really see a lot of dysfunctional bleeding.  As long as they have estrogen in their body naturally and their eggs can have any capacity to make them, you will still see spotting, bleeding. So, yeah, peri and menopause are a little different that way, but yeah. Contraindications and this is from North American Menopause Society, undiagnosed vaginal bleeding. So, obviously, if somebody’s just hemorrhaging and you don’t have an ultrasound, it’s important to do an ultrasound just to make sure nothing is wrong. So, obviously, before starting estrogen, if somebody’s having three-week long periods, do an ultrasound. First, diagnose. It doesn’t mean that you can’t give because progesterone will solve that problem for a lot of people. Yeah, but do the ultrasound first.

                                                Suspected or known BRCA genes really should not be taking any estrogen. Estrogen dependent cancers of any sort should not be taking estrogen. Acute liver disease, this is more for oral estrogen, but it’s implied in the packaging. It doesn’t mean that somebody can’t take this if they have fatty liver disease, for example. This would be something where the person is actually very sick at the time with something and then venous thromboembolic disease. It’s just a contraindication. So, that’s somebody with like a DVT or a PE at the time really.

Dr. Weitz:                            What about particular types of topical estrogen? So for example, estradiol versus estriol. Some people feel that estriol is safer, has less risk for maybe somebody who’s at higher risk for breast cancer.

Dr. McCulloch:                   Yeah, so compounded HRT is often called Biest, which is a combination of estriol and estradiol. The trend before used to give a large amount of estriol, so 80/20 where you were giving a lot of this estriol and the thinking was that estriol is protective against cancer. Estradiol is the bad estrogen and it’s going to cause cancer. But now, we actually have learned differently in that if you give too much estriol, it can block the receptors for estradiol and then you have to give more estradiol and you’re ending up giving much more than you need to. You’re just basically giving way too much.  So, now, mostly, they are 50/50 if you’re doing Biest. So, usually 50/50. I always target though to the estradiol when I’m looking at the dose, because that’s the one that makes the person feel better is generally estradiol. The estriol is there to mitigate risk and it can possibly help with some symptoms, but it’s very subtle compared to estradiol, which has a massive clinical effect for people. They used to have Triest, which was estrone, which is now not a good thing at all. Yeah. So, things have changed quite a bit with that.

Dr. Weitz:                          Well, in the category of women who are nervous because they feel like they have an increased risk of breast cancer, what about women who are afraid of taking estrogen, but they want to do something about the vaginal dryness and atrophy and stuff and they want to do something topically?  Some people have recommended topical intravaginal DHEA, intravaginal testosterone versus intravaginal estrogen and estradiol versus estriol. What do you think about what is the best and safest?

Dr. McCulloch:                   Yeah, those are all great. Actually, I have a slide on this. One second.

Dr. Weitz:                          Okay. Sorry.

Dr. McCulloch:                   No, I’m going to bring it up now because it’s like a perfect time too. But yeah, the DHEA actually is really a great option for vaginal tissue. So, it really can be used vaginally. It definitely can make a difference. The other thing is you can do just estriol with hyaluronic acid. That is a really good combination I use a lot. It’s very moisturizing, the hyaluronic acid. So, it retains the water and fluid. Then the estriol does have an effect in the local area. There’s also low dose vaginal estrogens like Vagifem, the very tiny amount. That works amazingly well. So, if it’s really just vaginal atrophy, dryness, that can be great. So, any of these can be awesome.  I think there’s the brand, they’re called something cube, I’m sorry. It’s in the US. We don’t have it here, but I wish we did. There’s these cubes. I think they’re called something cubes, and they have DHEA progesterone. I’ll get the name for you, but you can order them. They’re all vaginal, Bezwecken. They’re called Bezwecken Cubes. So, they have all these different types of vaginal treatments that are basically a variety of these different types of options that don’t have estradiol in them.

Dr. Weitz:                          Are those over the counter or those prescription?

Dr. McCulloch:                   They’re over the counter.

Dr. Weitz:                          Wow.

Dr. McCulloch:                   In the US. Yeah, they are. So, they’re really cool and they’re quite popular. Patients will say they’re very good. We just don’t have them in Canada, but I’ve heard a lot of the US patients tell me about that.

Dr. Weitz:                          Cool.

Dr. McCulloch:                   Yeah, so if I go to this slide, I just want to talk about the difference between estrogen and progesterone clinically and what you would expect to see because they have actually different effects. So, the estrogen, what you can expect to see that have an effect on hot flash, it’s like the best thing for hot flash by far. Some people will say progesterone helps with hot flash and it can, but not that much. It’s estrogen that really helps with hot flash. When someone is on estrogen, their hot flashes go away. It’s very intense on in its effect that way, even not at a very high amount. So, it really does help with that.

Dr. Weitz:                          Maybe you’re going to get to this, but what about supplements that might be beneficial for hot flashes?

Dr. McCulloch:                   I do have. Yeah.

Dr. Weitz:                          Okay. Well, hold the question there.

Dr. McCulloch:                   There are certain ones that are really good for hot flash.

Dr. Weitz:                          Okay, we’ll hold it.

Dr. McCulloch:                   Yeah. The vaginal dryness, really estrogen is the one for vaginal dryness, but you can do local estrogen like these Vagifem or these cubes or suppositories. You can do estriol. If estriol and something like hyaluronic acid or one of these other ones doesn’t work, you can try the low dose estradiol vaginally. So, vaginal dryness, it works amazingly. Bone density, same thing. So, mood is a big one. Estrogen really lifts the mood. It’s helpful for depression especially. So, a lot of people will feel their mood is so much better and they have more energy.

                                          I should have mentioned in this section two, libido in women is primarily driven by estrogen. A lot of people think it’s testosterone, but it’s actually estrogen that drives a lot of the libido in women. So, sometimes with the patients, you’ll give them testosterone or DHEA or something, because in women, DHEA turns primarily into testosterone. They don’t have any change, but you give them estrogen, all of a sudden, their libido’s amazing.

Dr. Weitz:                          Where does that myth come from that women’s drive comes from testosterones?

Dr. McCulloch:                   I mean, I think part of it does, but I think more of it is from estrogen.

Dr. Weitz:                          Steve says that’s because information comes from men.

Dr. McCulloch:                   Right, yes. That’s probably part of it. But if you think about estrogen rises at ovulation, that’s when you have a massive spike of estrogen. Right at ovulation, there’s a little rise in testosterone, but a massive rise in estrogen. It’s like that combination is probably what does it. So, yeah, but I always bring that up because sometimes people don’t think of estrogen that way. Then cognition, for us to say with 100% certainty, it does help that. We don’t have enough evidence, but there was another study that came out. It really looks like it is going to be a big thing for preventing Alzheimer’s and improving cognition. Too much estrogen replacement will cause breast tenderness, mood swings, sadness, crying, irritability, acne spotting, bleeding, weight gain around the waist and hips.

                                                So, those are over replacement. That being said, when you’re using topical estrogen in these amounts, which are not very high, it’s not that common to have that. Often, it’s just that you haven’t balanced it properly with the progesterone. Sometimes the high estrogen is actually coming from the person’s ovaries. The estrogen replacements we do in our Canadian units. I’m sorry, I don’t know the US conversion, but I’ll use the Canadian ones. Say at the beginning of the cycle, the estrogen’s about 100. At ovulation, it’s about 800. In the luteal phase, it’s about 400. So, when we’re using these topical estrogens, we’re putting people’s estrogens somewhere about 150 to 250. So, they’re nowhere near any of these reproductive levels.

                                                They’re at a low level, but sometimes their ovaries bust out an egg and makes a 1,500 of estrogen. That’s what causes those problems more so rather than these replacements. So, that’s where you’ll see it. It’s endogenous estrogen in perimenopause. Progesterone is essential with estrogen in anybody who has a uterus. If the person has their uterus removed, you don’t need to use progesterone. It’s not necessary to prevent the cancer risk. However, also, it has a lot of benefits. So, the first thing is it does oppose the estradiol. So, it thins the lining and prevents endometrial cancer. It is amazing for heavy bleeding. This is my top treatment for heavy bleeding. I use it all the time. It works so well.

                                                Vaginal or oral micronized progesterone and this is in perimenopause, I’ll often start with that and using a high enough dose that it’ll eventually stop the bleeding or turn it into light spotting. Once that happens, then you can start looking at estrogen if it’s needed, but it’s so amazing for menorrhagia and can prevent so many patients from having surgical procedures or going on other types of treatments. So, it’s something I use all the time. It’s great for sleep. It improves the depth of sleep. There’s a metabolite it turns into called allopregnanolone that can cross the blood brain barrier, and it does improve calmness, GABA, sleep. It’s very relaxing. So, a lot of patients will say, “Oh, I just slept so much better.” It doesn’t deal the hot flash as well as estrogen that wakes people up, but it definitely is very calming.

                                                So, the combination can be amazing for sleep. It does increase bone formation. Estrogen does a little bit more that way, but it definitely does that too, cardiovascular disease. So, it is really good for the endothelium. It’s anti-inflammatory. It also prevents coronary artery disease. Because of its anti-inflammatory effects, that’s most likely. So, it’s actually the opposite of synthetic progestin, which increases the risk of all of these problems. Over replacing bioidentical progesterone, it’s very interesting. The first month that you give somebody this, there’s something called crosstalk. If they have a high estrogen and they’re going to have more symptoms in the first month, that’s because their hormones…

                                                I always just explained to some that your hormones are ironing themselves out. They’re resetting. Hormones are complex because they’re all made by the ovary. These eggs have been going through different things ongoing. You have to wait for them to burn out and for the next stages to start. So, the over replacement symptoms are not often actually over replacement. They’re just initiation of progesterone in a high estrogen state. Secondly, too much progesterone could cause that in certain people, but we always give progesterone at bedtime, because consistently, oral progesterone makes people feel groggy and tired. It’s just the metabolites it turns into. So, vaginal does that far less and so does cream, but oral is quite likely.

                                                But when it’s given that bedtime, people are sleeping, so that’s great, they just sleep better. Then water retention sometimes, but that tends to resolve in time as patients get used to it as well. Then I just want to mention one more time that progestins are not the same as progesterone. There’s something called hydroxyprogesterone that sounds like progesterone. It really does, and even pharmacists can be confused about this. So, it’s really absolutely not the same thing as micronized progesterone. Very different altogether. So, always just make sure that it is actually micronized progesterone. Synthetic progestins, they all behave differently depending on the kind they are.

                                                Some of them actually proliferate breast tissue, and whereas natural micronized progesterone does the opposite. So, many of them increase the risk of clot. So, they’re all different, but they’re just substances that basically will thin the lining in the same way, but will not really improve the other elements that progesterone does. Androgens are a little complicated. So, because a lot of my practices in polycystic ovary syndrome where people have high androgens throughout their life, I actually see a lot of these patients who go through menopause. But what you’ll see is a lot of menopausal patients, even if they don’t have PCOS, they start to get androgenic symptoms. The reason for that is testosterone does decrease with age, but it’s gradual. Whereas these other ones, it is just like blam, none at all really compared to before.

                                                I mean, there’s a little bit left, but not much at all. But the testosterone’s still there. So, it becomes a more dominant hormone in the skin, for example, where it can exert things like hair loss or hair growth here. So, sometimes patients have this relative excess of testosterone, and sometimes you need to treat the DHT in the skin or treat it another way. Interesting thing is that progesterone is anti-DHT, so it is an anti-androgen. It can lower LH, which tends to encourage more testosterone. So, if a person has a lot of those types of symptoms, you can use progesterone as one of the treatments or things like saw palmetto, other types of herbs like that. But then there are some people who really do benefit from androgen replacement, DHEA, especially if they have very low DHEA, very low testosterone.

                                                If they don’t have these side effects, they can do really well with it. So, it just really depends on the person I find. I don’t want to be it too high in testosterone compared to the other hormones generally. The next one here was the DHEA. So, we already chatted about that, but this is a study, if you’d like to read it, just about DHEA and vaginal tissue. I’m just going to go into some of the herbs. There’s a category of herbs that I like to call endocrine adaptogens. So, that means that they basically help the endocrine system adapt to change. So, just adaptogens with the adrenals that help us adapt to stress and changes in cortisol, we also have herbs that either mimic hormones, fit into hormone receptors, or have hormone effects.

Dr. Weitz:                            If you don’t mind taking a question, Rosita is asking, “If a patient complains about weight gain when starting HRT, what can be done?”

Dr. McCulloch:                   Oh, yeah. So, normally, people lose weight when they start HRT. So, I would say I would look at what they’re taking firstly and be like, “Are they on a synthetic progestin?” Because that causes weight gain for sure. For most people, Provera causes weight gain guaranteed for almost everybody, like 10 pounds. Birth control pulls are the same. So, I would be like, “What’s their progestin? What kind of estrogen are they taking? Is it transdermal? Secondly, do they have something else going on their thyroid, for example?” Because estrogen affects the thyroid quite a lot. When you give estrogen, it binds thyroid. Thyroid binding globulin goes up when estrogen goes up. So, sometimes just the menopause and then going out of it will bring up that element.  So, I would just assess every single thing and see why that might be happening. Because normally, they should actually lose weight on estrogen, especially. Yeah.

So, these are our endocrine adaptogens. These affect our hormones. So, the sex hormones primarily, estrogen, progesterone, testosterone, these ones here. So, the left-hand side, these are androgenic herbs. They have androgen promoting effects primarily in women, which are different than in men. So, some of the herbs that we’ll see for men and women are just a little bit different because androgens can have dimorphic effects. So, they’re like maca, tribulus, Panax ginseng, damiana, epimedium, bacopa and Gotu kola. These tend to be more like stimulating testosterone types of promoting herb. So, people who have low libido, fatigue, energy.   On the right side are the kinds of estrogen, progesterone types of herbs that really help with these symptoms related to those problems. So, hot flashes, vaginal dryness, menstrual symptoms, insomnia and mood, any symptoms of estrogen deficiency. So, shatavari is tonic generally from Ayurvedic medicine. It’s a really great herb I find for perimenopause, for mood, skin, hair, hot flash energy. Black cohosh is very famous for perimenopause and menopause. It used to be thought of as being a phytoestrogen, but now, actually, they believe it works in the brain and not as a phytoestrogen. Wild yam, dioscorea is often thought of as mimicking progesterone, but it actually has to be converted into progesterone in a lab.  It can be, but it is not progesterone. In fact, it seems to have effects on estrogen primarily. Siberian rhubarb is one of the phytoestrogens that is most effective for hot flash. So, that is my top one that I usually recommend for a hot flash right now. So, I really like Estrovera by Metagenics for this, and they actually have a guarantee. If it doesn’t get rid of the hot flashes within two months, I think it’s two months, they’ll give you your money back or reduce them. It does work, I find, not as well as estrogen, but for people that can’t take it, I find this extract is pretty good for hot flash. Red clover is another phytoestrogen. Vitex is probably one of the most misunderstood herbs. It’s thought of as being progesterone, but actually, Vitex is not directly progesteronic. It’s those that research is because it can encourage ovulation in certain situations, which increases progesterone. But for the most part, Vitex acts on dopamine and prolactin in the brain. So, if somebody has amenorrhea and stress, often they have high prolactin. If they have hypothalamic amenorrhea, this is a helpful herb. So, if there’s like a mood component and a change in cycles, it can be helpful, especially with prolactin being high. Kudzu is another phytoestrogen. It’s quite strong, I find. So, for hot flash, it can be useful. Dong quai is from traditional Chinese medicine, Angelica. I find it similar to shatavari. It’s like a tonic generally. Hops is another phytoestrogen.

                                                Okay, and the next section is the adrenal adaptogens. I like to include these because they’re super important. They’re just a little bit different than the endocrine adaptogens. The first one is Ashwaganda, Withania somnifera. This is my favorite adaptogen for stress and sleep and for anxiety. It’s a very calming adaptogen. It takes it down a few notches. It’s great to give it bedtime, to keep people from waking up in the night from a cortisol spike. So, that is my favorite way to use Ashwaganda, or I also give it in the daytime for people with anxiety, irritability. Holy basil is a really nice herb because it really is a good mood booster in perimenopause. Plus, it has some really nice effects on skin and hair. So, a lot of patients like it.   Eleutherococcus is a really great adaptogen. I always think of it as a stress shield. So, if life is stressful and you’re on eleuthero, you will not feel the stress as much. It gives energy. It’s a really good tonic. It’s great for people who want to start working out. So, I do really like an eleuthero. Rhodiola is a very uplifting herb, so I find it’s very good for people with low cortisol or depression or fatigue, dopamine problems. It can help with attention, brain fog. Panax ginseng actually is quite similar to it’s uplifting, stimulating. For people who have more anxiety, it might not be the right fit, but for people with a lot of fatigue and low testosterone, it’s a really good one. Then sage is really good just for mood, energy, overall cortisol balance.  So, often it’s added into formulas, herbal formulas.

                                                  The next slide, sleep and mood. So, sleep and mood, I want to include some of the natural treatments here because it’s probably one of the most common complaints. So, on the left side, I have some of the treatments I tend to use for insomnia. Now, of course, HRT is going to have the biggest impact on this because it just resolves it so well for so many people. So, I always start with progesterone if they’re open to it because it helps so much. But magnesium, melatonin, these melatonin with sleep onset. Magnesium is just something that is one of those general supplements that everybody should be on if they’re having a sleeping problem because most people are deficient in magnesium and the herbs.  So, there are many herbs that you can use for sleep, valerian, skull cap, passionflower. Zizyphus is one of my favorite herbs for sleep. It’s often not even considered, but it’s a great herb from traditional Chinese medicine for sleep. Then Withania, so Ashwaganda. So, I use that a lot at bedtime. I really like the Douglas Labs’ Ayur-Ashwaganda, so I just find that extract really good. Two of those at bedtime is really helpful for preventing the 3:00 AM wake up. Anxiety and irritability, so of course there’s so many options here too, but we’re looking at all of these nutrients like GABA, threonine, phosphatidylserine, taurine.  Again, Ashwaganda, St. John’s wort, which you can’t combine with SSRIs and Vitex actually helps quite a bit with irritability and anxiety and other kinds of mood effects. That is all that I have presenting to present today. So, do you have any questions? I’m happy to answer.

Dr. Weitz:                          Yeah, no, that was great. Excellent. Good information.

Speaker 3:                         I got a question, Ben.

Dr. McCulloch:                   Yes.

Speaker 3:                         My wife is on 0.0125 Vivelle-Dot estradiol, and she’s on compound microdose pharmacy 100 milligrams of progesterone. She’s been on that since menopause. She’s doing fantastic. The question is about pulsing that. Some people say not to, some say to do it. We haven’t done it. She’s doing great as she is. Is there any problem with that Vivelle-Dot? She’s doing great.

Dr. McCulloch:                   I don’t think that there’s any reason that we’ve ever learned that it should be pulsed. Sometimes that makes people bleed and spot. So, they used to be like, “Oh, the receptors.” But what we know is that reproductive age women always have estrogens. The receptors don’t go away just because the estrogen is at a certain level. When the estrogen goes away, the receptors go away. So, keeping the estrogen there is probably better for the receptors, but they’re very-

Speaker 3:                         How long will she have to be on this, the rest of her life far as I’m concerned? I mean, when she’s 95, we’ll stop it.

Dr. McCulloch:                   Well, right now, what we know is that it’s safe up to 10 years. It’s safe up to five years after the last period with progesterone if it were a synthetic progestin. We don’t have enough data to say that natural progesterone is safe past that, but it probably is because it’s never been shown to cause clot. So, they’re going to have to have the research to show that it’s safe to 10 years like estrogen and then we don’t know beyond that point actually.

Speaker 3:                           Wow. So, she’s going over 10 years. Oh, wow.

Dr. McCulloch:                   There’s lots of people on it past 10 years and they’re generally doing very well. I think this is just the research has to be done.

Speaker 3:                         Thank you.

Dr. McCulloch:                   Yeah. When I graduated school, there was doctors doing HRT in our city and they have had patients on it for decades doing well. So, yeah.

Speaker 3:                         Thank you.

Dr. Weitz:                          What about, is there value in tracking the estrogen metabolites through the urine testing to see how they’re metabolizing it and then using particular supplements to try to influence that to make sure that they’re metabolizing it along the safest possible pathways?

Dr. McCulloch:                   Yeah, exactly. So, I think you can do the DUTCH test, take a look at what’s happening there, if there’s anything risky. Breast cancer is complex. It’s not estrogen. It’s the entire situation and then estrogen just feeds it, but that can be done. Then just the dose is generally so small in these groups. We don’t use large doses. The older people get, the less these large doses are ever going to be needed. So, it’s like a tiny baseline just to prevent the receptors from going away and give that little bit of stimulation. So, there’s probably lots of ways to make it very much safer.

Dr. Weitz:                          I mean, I know there’s a concern that as women go through menopause, there’s an increased risk of bone density. Do you recommend particular strategy, supplements during that period to maximize bone density or limit bone loss?

Dr. McCulloch:                   Yes, 100%. So, the HRT definitely is a huge thing that is the top thing. Then a really good bone mineral formula, something that has the whole array of nutrients, something like we have here, Ortho Bone, but there’s so many other products like this out there. I know we have a lot of Canadian products, but one of those bone formulas that has a good quantity. Then exercise is critical. I recommend exercise for everybody. Even if someone isn’t that mobile, there’s also whole body vibration that’s been shown to have a lot of effect on osteoporosis.  Anyone can do that really. You can get the plates at home. Even somebody who’s disabled can do that. So, there’s lots of things like that that can be done and phytoestrogens might help, but it’s not a lot not compared to estrogen.

Dr. Weitz:                            Rosita asked about using DIM for estrogen dominance or PMS symptoms.

Dr. McCulloch:                   DIM is a really good supplement to lower high estrogen. So, somebody consistently has high estrogen and perimenopause, it can be really good. It can also direct it down a less harmful pathway to be eliminated. Making sure no constipation is very important too, so that it doesn’t get reabsorbed back in the gut. You can use calcium D-glucarate to make sure that that happens too, because it keeps it from breaking down basically in the gut and getting reabsorbed. So, someone has a gut issue, high estrogen, you probably want to deal with constipation and add D-glucarate with the DIM too.

Dr. Weitz:                          Now, I have talked to some doctors who say every time they put women on HRT, they automatically give them DIM and calcium D-glucarate and iodine or something like that.

Dr. McCulloch:                   Yeah. I don’t tend to do that because DIM lowers estrogen. So, sometimes that can be not a good thing and that you’re giving it and it’s going out. So, you have to know what’s the reason for that. Because DIM as a concentrated supplement is very different than eating those vegetables that have I3C. So, I usually do that in a response to something very specific I’m seeing.

Dr. Weitz:                          Right, yeah. Treat each case specifically. Allison is asking about AMH levels in perimenopause.

Dr. McCulloch:                   So AMH levels in perimenopause are always low. They’re never going to look good unless someone has PCOS. In some cases, they actually still have really good AMH, so they tend to go through menopausal later. But for most people past age 40, there’s really not a lot of point of testing AMH because it’s just going to look low. You can already tell from their age and their pattern of their cycles if they’re in perimenopause, but in a younger woman, sometimes you can’t tell that’s what’s going on. It might be they have stress, they lost weight or something else.  It’s causing the cycle irregularity. In perimenopause, it has a pattern like it’ll shorten and it’s consistent. It doesn’t go back. It just continues that way, marching along towards the end. So, you can do it and it just depends on the situation. If you’re really not sure, you can definitely do it, but it should be very low.

Dr. Weitz:                          Okay. So, I think we’ll conclude. Thank you so much, Fiona. It was awesome.

Dr. McCulloch:                   Thanks. I’m glad it was helpful.



Dr. Weitz:                            Yes, absolutely. Thanks, everybody, and we’ll see you next month. Thank you for making it all the way through this episode of the Rational Wellness Podcast. For those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcasts or Spotify and give us a five-star ratings and review. That way, more people will discover the Rational Wellness Podcast. I wanted to let everybody know that I do have some openings for new patients so I can see you for a functional medicine consultation for specific health issues like gut problems, autoimmune diseases, cardiometabolic conditions, or for an executive health screen and to help you promote longevity and take a deeper dive into some of those factors that can lead to chronic diseases along the way.  That usually means we’re going to do some more detailed lab work, stool testing, sometimes urine testing, and we’re going to look at a lot more details to get a better picture of your overall health from a preventative functional medicine perspective. So, if you’re interested, please call my Santa Monica Weitz Sports Chiropractic and Nutrition office at (310) 395-3111, and we can set you up for a new consultation for functional medicine. I’ll talk to everybody next week.


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