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Ovulation Disturbances with Emma Sutherland and Dr. Jerilynn Prior

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Ovulation Disturbances with Emma Sutherland and Dr. Jerilynn Prior

Ovulatory disturbances pose significant challenges to women's reproductive health, making it crucial that practitioners have a comprehensive understanding of this complex topic.

In this episode, Professor of Endocrinology and Metabolism Dr. Jerilynn Prior and our Ambassador Emma Sutherland provide clinicians with essential insights into the causes, diagnostic indicators, hormonal balance, and potential interventions associated with ovulatory disturbances. 

Together they discuss why ovulatory disturbances are not diseases but adaptive responses to a variety of factors –both biological and environmental, including work-related stress, lack of close relationships, time-related pressures, and feeling undervalued. Dr. Prior shares some clinical pearls to assess ovulation and relative hormone levels through cervical mucus observations and breast tenderness as well as compelling research surrounding the impacts of COVID and the importance of resilience.  

Recognising ovulatory disturbances as adaptive responses and educating patients about their reversibility are key steps towards effective management strategies. 

Covered in this episode

[00:34] Welcoming Dr. Jerilynn Prior
[01:43] What is ovulation?
[02:43] Ovulatory disturbance is usually silent
[04:00] Is basal body temperature an accurate measure of ovulation?
[07:09] The inaccuracies of Day 21 progesterone testing
[11:10] Common causes of ovulatory disturbances 
[13:48] How stoping the OCP impacts ovulation
[15:22] Ovulation disturbances are adaptive and preventative measures
[18:54] Determining an non-ovulatory cycle
[22:32] Long-term issues associated with ovulatory disturbances
[27:12] How many women are experiencing ovulation disturbances?
[28:32] Ovulatory disturbances and risk of early heart attack
[29:47] Impacts of COVID on ovulation and the menstrual cycle
[34:33] Treatment for ovulatory disturbances
[36:19] Cyclic progesterone therapy
[42:06] Resources for practitioners
[43:47] Final remarks and thanking Dr. Prior


Key takeaways

  • Ovulation is the release of an egg from the ovary; however, a regular normal-length cycle does not guarantee ovulation is occurring. 
  • Ovulatory disturbances are not ‘diseases’; they are adaptations that can be reversed and modified. Ovulation and menstrual cycles naturally adjust to the circumstances and stages of our lives. These changes serve as a protective mechanism, although they may not be ideal. 
  • Urine progesterone levels vary due to genetic factors, with East Asian women metabolising and excreting this hormone faster than Caucasians. 
  • Common – and likely unrecognised causes of ovulatory disturbances - include feeling undervalued, lacking close relationships, work-related stress, and time-related pressures. 
  • To accurately test for blood progesterone levels or luteinising hormone , observing mid-cycle cervical mucus can provide helpful indicators. Stretchy and clear mucus with the ability to create a longer thread between the thumb and index finger suggests higher oestrogen levels. Breast tenderness can serve as an indicator of elevated oestrogen levels in the body.  
  • Instead of focusing solely on oestrogen deficiency, clinicians must consider progesterone as an equally important hormone and both need to be in balance. The imbalance between these hormones is often a protective response to the environment so it's important we educate our patients that this is not a disease state and can be corrected. 
  • Women who experience ovulatory disturbances may lose cancellous spinal bone. This is because during the menstrual cycle, when oestrogen levels drop, bone loss occurs. Opposing this effect with progesterone can stimulate new bone formation and prevent net bone loss.  
  • Studies indicate that the impact of COVID on ovulatory disturbance is countered by increased resilience. Women with higher resilience levels tend to maintain normal ovulation. 
  • Cyclic progesterone can be used temporarily until the menstrual cycle normalises. Cyclic progesterone therapy: can be utilised for as long as required, and improves many symptoms of hormonal imbalance, helping to build resilience, reinstate the ovulatory cycle and most importantly, safe. 

Resources discussed and further reading

Dr. Jerilynn Prior
The Centre for Menstruation and Ovulation Research
Clinical tool: The Daily Diary: Menstrual Cycle Tracking (CeMCOR)
Clinical tool: Documenting Ovulation with Quantitative Basal Temperature (QBT) (CeMCOR, 2014)
Article: Ovulatory Disturbances: They Do Matter (Prior, 1997)
Opinion Article: Adaptive, reversible, hypothalamic reproductive suppression: More than functional hypothalamic amenorrhea (Front. Endocrinol., 2022)
Article: Progesterone is NOT a Progestogen/Progestin— It’s Estrogen’s Unique Biological Partner (CeMCOR, 2016)
Article: Cyclic Progesterone Therapy (CeMCOR, n.d.)
Article: Why Is “The Pill” Harmful for Bones in Adolescent Women? (CeMCOR, 2019)

Abstract: Epidemic of Subclinical Ovulatory Disturbances During SARS-COV2 Pandemic—an Experiment of Nature (Prior, et al., 2022) 


Emma: Hi, and welcome to fx Medicine, where we bring you the latest in evidence-based, integrative, functional, and complementary medicine. 

I'd like to begin by acknowledging the traditional owners of the land on which we record today. I would also like to pay my respects to elders, past and present. 

With us today is Professor Jerilynn Prior, professor of endocrinology and metabolism at the University of British Columbia in Vancouver. She has spent her career studying menstrual cycles and the effects of the cycles changing oestrogen and progesterone levels on women's health. 

In 2002, Professor Prior founded the Centre for Menstrual Cycle and Ovulation Research, which is the only centre in the world that focuses on ovulation and the causes for and health consequences of ovulation disturbances. Today, we're going to take a deep dive into ovulation disturbances. 

Welcome to fx Medicine, Jerilynn, and thank you so much for being with us today.

Jerilynn: Oh, I'm happy to be here.

Emma: Now, as clinicians, we hear our female patients describing their menstrual periods, and what astounds me is the variability within them. And I feel like the menstrual cycle is like a woman's fingerprint, no two are the same. 

Now, Jerilynn...it's true. Can we start with ovulation itself? How is ovulation officially defined?

Jerilynn: I think that's controversial. You'll find apps that tell you with great seriousness that they can do it, and doctors will say the same, and women who will say the same, but really it's not an easy thing to do. And ovulation is the actual release of an egg, but most of the time women don't know and clinicians don't know when and whether that has happened.

Emma: Okay. This does make it confusing for everyone, doesn't it?

Jerilynn: It does.

Emma: So, what are the signs and symptoms of ovulatory disturbances, and what are actually the most accurate methods to diagnose them?

Jerilynn: The problem with ovulatory disturbances, and I use that term because I don't want us thinking about them as a disease. They're adaptations, they're reversible, they're changeable like a finger...well, our fingerprints don't change within a person, but ovulation and cycles do change and adapt to whatever circumstances we're experiencing in our lives or where we are in our life cycle. So, think of the changes as protective, but not optimal. 

Okay so, the problem with ovulatory disturbances is that they're usually silent, or as we say in medicine, subclinical. In other words, we don't know. If we're having a perfectly regular cycle, and it's about a month apart, we don't know when we don't ovulate normally, and that's a problem.

Emma: It is. How useful, in your opinion, is basal body temperature charting also called quantitative basal temperature for highlighting ovulation disorders? Because often we do ask our patients to track their temperatures.

Jerilynn: Okay. There's a big difference here. So, the typical kind of use of the first-morning oral temperature, or BBT as it's sometimes called, is unfortunately not very scientific, not reproducible. Different experts will grade the same data differently. 

So, what I did a long time ago when I didn't have money to measure progesterone or oestrogen or other hormone levels, and women didn't want to come in and get the blood tests, was I took the old-fashioned basal temperature and made it into something quantitative and valid.

Emma: Okay.

Jerilynn: So, we compared it, for example, in a blinded manner versus the serum LH peak in women who are having a blood test at the middle of the month daily, and showed there was a comparison about 0.9, which was very good. And we later compared it with the...I don't know if you're familiar with the urine method of assessing pregnanediol, the excretion of progesterone or the excretion of oestrogen in the urine. And in fact, the quantitative basal temperature method we have was more reliable than the urine method. The urine method was more likely to say a cycle was ovulatory when it wasn't.

Emma: Oh, that's interesting. And so, how does a woman actually do quantitative basal temperatures?

Jerilynn: Well, what we've done is to put a place on the menstrual cycle diary at the bottom for writing the temperature in. And we've now made it so in studies that women can do that online, they don't have to do it on paper. And then at the end of that cycle, all of the temperatures in that given menstrual cycle are averaged, and where the temperature goes above and stays above the average temperature until the next flow is called the luteal phase.

Emma: Right. Okay.

Jerilynn: That's a method that we have reported and is accessible to women on the CeMCOR website, the Centre for Menstrual Cycle and Ovulation Research site. It's sort of in the middle of the page, just below the daily diary forms.

Emma: We will link to that directly so that we can all access that information because I think it's really pertinent. For all the clinicians that are working with women on their cycles, this is a validated method for determining ovulation. This is a great resource for us.

Jerilynn: Yeah, I think so.

Emma: You mentioned before about the urinary progesterone and working out, I think there's some correlation with the threefold increase between follicular and luteal. 

Do you still think progesterone is a valid marker? Because, especially here in Australia, most of the time it's a day 21 blood test for progesterone, which we know is wildly inaccurate for a lot of women. But what sort of guidelines would you recommend on this progesterone side of things?

Jerilynn: Yeah, it's a problem. It's a real problem. The issue that we found with urine progesterone is that because it requires....you have to excrete it in the urine, which means that it has to be linked with glucuronide, and there are different genetic characteristics that lead to different urine output of this pregnanediol glucuronide. For example, East Asian women, Chinese, Japanese, Korean, etc., will metabolise and excrete progesterone, oestrogen, and some drugs much more quickly than Caucasians will.

Emma: Okay.

Jerilynn: And having a test that's different by race and, unfortunately most people don't realise that, is just not okay.

Emma: Yeah, and this is incredibly problematic because depending on the woman sitting in front of you, the urine level could be very different. And then the blood levels are often very different as well because women aren't explained when they should go and get that test done. They're just simply told on day 21, which is not always the right time for a woman to have her blood progesterone checked.

Jerilynn: That's true. Quite true. And in one cycle she can ovulate on...well, in perimenopause, for example, one time, I ovulated on day 10 of my cycle, and the next cycle after that, I ovulated on day 29.

Emma: Right. Yeah. Very tricky.

Jerilynn: So, one of the ways that I found that's helpful in telling women if you're going to use either the LH test or a blood test is to try to pay attention to the mid-cycle cervical mucus. The stretchiness of it, it should be egg white and clear. And the longer a thread you can make if you put some on your finger and put your thumb and your finger together, the longer the thread you can make, the higher the oestrogen level. Actually, that was John Brown, who's an Aussie guy who first observed that.

Emma: And then to wait seven days and then do their blood test?

Jerilynn: Yeah.

Emma: Yeah.

Jerilynn: Or from the maximum of the stretchy mucus. Sure.

Emma: Yeah.

Jerilynn: And the same is don't start testing for your evening LH pee test until you've had stretchy mucus for a few days.

Emma: There you go. They're really good guidelines for us to be sharing with our clients and making sure that they're doing these tests on the right time. I mean, what about those...

Jerilynn: Because it's so frustrating to take a day of the cycle and say, from day 10 until I get a positive LH test, I'm going to keep doing it every night. And it's so frustrating for women and expensive.

Emma: Yes, exactly. That's right. And I think, from my point of view, when you're working with women, they tend to start losing faith in their body because it's not acting as they feel it should, the same every single month. And that's...

Jerilynn: That's because we're not teaching them properly.

Emma: Yeah, exactly. We need to be highlighting this. 

What do you think are the sort of most common physical or psychological drivers for ovulatory dysfunction?

Jerilynn: That totally varies depending on the person and also depending on their reproductive maturity. So, in the adolescent, the main reason is that they haven't yet developed the connections between the brain and the pituitary and the ovary that need to be connected before ovulation becomes routine. In women who are into their early 20s, predominantly depends on whether they're adequately nourished, and their social, emotional sense of support and health.

Emma: Yeah.

Jerilynn: The most common causes for ovulatory disturbances, in general, nowadays, are simply not feeling valued, or not having people that you're close to, or under work-related, or time-related stressors, things like that.

Emma: Yeah, and in this current day and age and climate, that is many women. And I love the fact that you pointed out with adolescents, they've not yet developed that HPO axis, and these are the young patients that we often see coming in to see us that have just been told to go on the pill to regulate their cycle. And I think...

Jerilynn: That's taking a sledgehammer to fix a problem with a tiny screw.

Emma: Yes.

Jerilynn: It's really silly and it does not assist that young woman's cycle to develop normally. In fact, it may delay it or prevent it.

Emma: Yes, and then we can see future fertility issues in that woman as well. Yeah. A lot to be said for counselling our young patients around those decisions, isn't there?

Jerilynn: You didn't ask me the question, but I'm going to tell you that the evidence that using the pill in teenagers is not good for bones is pretty strong because it's a high enough dose of oestrogen that it interferes with development of peak bone mass.

Emma: Wow.

Jerilynn: We showed that in a meta-analysis published in 2018, I think.

Emma: I think that's quite astounding, and I don't think that people are aware of that.

But how does coming off the pill impact ovulation?

Jerilynn: Oh, that's a good question. We know from a study that was done in Germany of women who were keeping track of their fertility and natural fertility type cycle tracking, and it appeared that it took about nine months from stopping the birth control pill before the average woman became pregnant, who was looking for pregnancy, obviously.

Emma: Yeah.

Jerilynn: And it took only about three cycles for someone stopping something like barrier methods.

Emma: Oh, wow. That's a big difference.

Jerilynn: Yes, it is.

Emma: What do you think mechanistically, what is going on there?

Jerilynn: Well, I think of oestrogen as a huge and powerful medicine. And it obviously has to be higher than physiological in order to stop our body from ovulating and prevent pregnancy. But it basically just puts this huge weight on the coordinating system in the hypothalamus and the pituitary.

Emma: Yeah. And I think nine months, that is a good amount of time to be telling women, "Look, it can take this long. Maybe there's not something sinister or anything else going on, we just need some time to nourish your body and really help support the communication channels there in the brain."

Jerilynn: Mm-hmm.

Emma: Now, you have just written an opinion piece that I've read this morning. You wrote it in an endocrinology journal on this topic of ovulatory disturbances. And I found it, I have to say, just an incredible read and we will link directly to that in the show notes. But can you talk us through that opinion piece and what you discussed in there? Because I think it's information that people are not aware of, Jerilynn.

Jerilynn: Okay. What has often bothered me is that we talk about missing periods or amenorrhea or long cycles or oligomenorrhea as though they were diseases, and we consider them to be oestrogen deficiency. But we forget that they also don't have enough progesterone or they don't have any progesterone, and we totally ignore the disturbances of ovulation that happen within a regular cycle. Like, not having a normal length of the ovulatory or luteal phase or insufficient progesterone production or not ovulating at all. And we don't recognise, as we've been talking about, that those are even occurring because they often occur or almost always occur in perfectly regular cycles. 

So, what I was trying to do is to say, let's stop thinking about oestrogen deficiency, let's start thinking about the two hormones, oestrogen and progesterone, as being partners and needing to be in balance and think about the reasons why they may not be. And those reasons aren't usually diseases, they're sort of protective responses to an environment that's not happy for the person.

Emma: Okay.

Jerilynn: So, thinking of them as adaptive and as preventative, the body isn't doing things wrong, it's doing things very right to try to make sure that as an individual you can manage during this tough time.

Emma: And I think that's a profound shift of thinking for us to then recategorise things like, amenorrhea, oligomenorrhea, normal cycle without ovulation, or normal cycle with a short luteal phase to then categorise them as, this is the body trying to protect itself from a stressor of some kind.

Jerilynn: Yes. And thinking of them as adaptation also takes away this sort of idea that women are particularly vulnerable, that women are weak. Well, that's a strong and positive response. It's protecting us from becoming pregnant at a time when we should not, for the sake of not only our own health, but in terms of family, or in terms of a clan, or a band of people. It would be hard on everyone if that woman became pregnant.

Emma: Yes. It's the ultimate protective event, isn't it? When you take it back to that tribal level about how we are still hardwired in this same way.

Jerilynn: Yeah. It's a long-established and very fine-tuned process. It's just we who've been a little stupid and calling it things like the female athlete triad or something like that.

Emma: Yes, interesting. But I'm curious, a little bit confused, but also so curious, how do we determine a non-ovulatory menstrual cycle compared to an ovulatory menstrual cycle? I mean, as clinicians, what are the things that we need to be looking for to tell us, "Okay, this was ovulatory or this was non-ovulatory?"

Jerilynn: I wish I could say. The closest guess that I can make at the moment is that if someone notices that kind of mid-cycle stretchy mucus mixed up with her menstrual flow, it's likely she didn't ovulate that cycle.

Emma: Okay.

Jerilynn: Okay. The reason is, as you know, the stretchy mucus is made by the effective oestrogen on the cervical glands. But progesterone inhibits that creation of cervical mucus. So, if progesterone's around, you shouldn't see stretchy mucus before flow.

Emma: Okay. That right there is an excellent key takeaway for us all, and to be specifically asking that question of our patients and getting them to start tracking their cervical mucus. Yes. That is fantastic. Thank you.

Jerilynn: I think another probable one is, so, again, another sign that women can use is if you push the flat of your hand, the palm of your hand into your breast, right over your nipple, push it toward the back of your spine, it shouldn't hurt at all. And if it hurts at all, the oestrogen level is higher than the mid-cycle peak.

Emma: Okay.

Jerilynn: So, if you had breast tenderness, and so, again, oestrogen increases breast tenderness, progesterone probably inhibits it, so, if you had breast tenderness right before flow, you're probably not ovulating or ovulating normally.

Emma: Okay. So, could that also mean that somebody is ovulating but having a short luteal phase?

Jerilynn: Sure.

Emma: Yes.

Jerilynn: Yeah. So, somebody with a short luteal phase has ovulated, they just didn't make enough progesterone for long enough.

Emma: Okay. Fantastic. So, two clinical pearls there is mid-cycle type mucus within the menstrual flow, as well as breast tenderness before the menstruation are key signs that a woman may not be ovulating.

Jerilynn: That's right.

Emma: Okay. Thank you.

Jerilynn: That's the best we can do at the moment. I don't know if I told you, but we had a group of women who were perfectly normally ovulatory and normally cycling, two consecutive in a row, normal body weight, non-smokers, years ago whom we followed for a year. And they kept the basal temperature, they also kept the diary. And so, we're now individually analysing those data to try to get from that information to learn more about how women and clinicians can use these experiences, and also, what do you expect in a normal cycle?

Emma: We would be fascinated to see that information come out when it's all been collected and analysed, Jerilynn.

Jerilynn: Yeah. Yeah, I think it's important.

Emma: Yeah. It's pivotal. It's absolutely pivotal. 

What are the long-term problems associated with ovulatory disturbances? And what is the mechanism here? Obviously, we are not making enough progesterone in relation to oestrogen, but what's wrong with that?

Jerilynn: Okay. Well, have to go back to square one here.

Emma: Yeah.

Jerilynn: Oestrogen is a powerful hormone and its primary and continuous effect is to make cells proliferate, or grow, or get larger, or more of them. And that, as you would suspect, runs the risk of genetic errors and cancers. Now, progesterone, it turns out, in most cells and most tissues, may have a very short time in which it causes cell growth, but its primary job is to inhibit proliferation. And therefore, it needs to slow and stop oestrogen's unwanted or persistent proliferative or growth-stimulating effects.

Emma: Okay.

Jerilynn: So, the two are meant to be balanced, and they both have actions everywhere in our body. So, we think about oestrogen as affecting the brain and the heart, and breasts, obviously, but we don't often think about progesterone as having similar effects, but it does. So, we know already that if you don't have enough progesterone, that you're not likely to get pregnant. That's the number one. And there are so many women who are having trouble getting pregnant now. Many of those are unrecognised ovulatory disturbances.

Emma: Okay.

Jerilynn: Okay, that’s the first one. Then the original study that I told you about, I did it in the mid-80s and published the article in The New England in 1990 showed that women could have perfectly regular cycles, be stable in weight, have enough calcium, exercise properly, etc., and still be losing spinal bone.

Emma: Right.

Jerilynn: Actually, this was before DEXA. We were using the quantitative computed tomography, in other words, an ordinary CT machine, but using it to look at the centre of the vertebral body where cancellous bone is.

Emma: Okay.

Jerilynn: So, why would women who have enough oestrogen be losing bone? And we found there was a direct relationship with progesterone. If they had ovulatory disturbances, so a short luteal phase twice in a year or more, or any non-ovulatory cycles in that year, they were losing this cancellous spinal bone. 

So, the question is, why would that happen? Well, oestrogen - if you can picture the typical menstrual cycle in your head - oestrogen makes it a peak at the middle of the cycle, that's to trigger the LH peak and then trigger ovulation. And then it decreases about half during the luteal phase, and then it decreases down to a quite low level during flow.

Emma: Okay.

Jerilynn: So, it's dropping from the middle of the cycle all the way down until flow. Well, oestrogen stops bone loss when it's steady or high, but it causes bone loss when it's dropping.

Emma: Okay.

Jerilynn: So, in the time when it's dropping, you need progesterone to stimulate new bone formation, which it does by acting directly through the osteoblasts in order to prevent there being net bone loss.

Emma: Okay. So, there's probably a lot of women walking around out there that are at risk for osteoporosis and are not aware of it.

Jerilynn: Exactly. Thankfully, most women have a few the odd anovulatory disturbed cycle and then the rest are fine. And that, in fact, one of the things that we're learning is that we need at least two-thirds of our cycles, and preferably, three-quarters of our cycles to be normally ovulatory, to not be at risk of these problems with bone and infertility, etc.

Emma: And, Jerilynn, do you know of women that, healthy women, what is the percentage of these women that are getting ovulatory disturbances? Do we know that yet?

Jerilynn: There aren't very many long studies, but we did a meta-analysis of all the ones we could find a few years ago, and that's the data that shows that, by DEXA, about 1% bone loss happens in women within each cohort who had a higher than the average for the whole cohort percentage of ovulatory disturbed cycles.

Emma: Right.

Jerilynn: So, I would guess that about a quarter of us at any one time are having an ovulatory disturbed cycle.

Emma: Yeah, okay.

Jerilynn: I say of us, and I'm well past that now, but I mean of menstruating women.

Emma: Yeah. That actually really shocks me, but it also horrifies me a little about this unknown epidemic that is going on without the awareness of clinicians and women themselves.

Jerilynn: I know. And unfortunately, it is not helped by gynaecology, at least here. They say, "If you've got a regular cycle, don't worry, dear."

Emma: Yeah. It's similar here, Jerilynn.

Jerilynn: That's false reassurance, unfortunately.

So, we were talking about the consequences of having more than the average of ovulatory disturbed cycles, and I mentioned infertility and I mentioned bone loss. In addition, there's pretty strong evidence that there's a risk for early heart attack.

Emma: Oh, okay.

Jerilynn: This was a big population-based... Actually, it wasn't. It was a mammogram study, and they asked women to collect their urines for three cycles in a row on day 22 of their cycle. And then they followed all the women for heart attacks as they got closer to menopause and into menopause, and then checked and found that the ones who had heart attacks early, some were not menopausal, others were early in menopause, that they were less likely to have ovulatory cycles or to have low progesterone excretion in the urine.

Emma: Okay. So, the importance of...and it's no wonder you have established a whole centre focused on this, and I can hear and feel the passion in this topic for you. It's astounding. It's something that we all need to be talking more about. 

I wanted to talk to you about COVID. And as clinicians, we've all seen changes in our patients, and possibly, even our own menstrual cycles over the last couple of years. And in June this year, you presented a paper titled ‘Epidemic of Subclinical Ovulatory Disturbances During SARS COVID-2 Pandemic and Experimented Nature.’ And in the paper, which we will link to, you compared two data sets, one from 2007 and one from over the pandemic time.

This is fascinating information. I would love it if you could discuss for us what you documented, and what you uncovered here.

Jerilynn: Okay. The bottom line of the story is that during the pandemic, most women, 91% - and the number that we had originally was 124, but we have complete data for 108. So, 91% of the cycles were normal length, but 63% were not normally ovulatory.

Emma: Okay.

Jerilynn: And I haven't yet gotten that published. It's complicated data set. We had a whole bunch of information on living alone, whether they ever had children, how many years of education, their ethnicity, etc., all kinds of things, whether they used the birth control pill, when they started it, at what age, etc. Anyway, basically, almost everything we looked at was not related to whether they ovulated normally or not.

Emma: Okay.

Jerilynn: Eventually, we found that if they had a normal body weight, they were more likely to ovulate normally. We also found that women who reported that they had a regular exercise program despite the pandemic were more likely to normally ovulate. And ironically, those with fewer years of education, but let me quickly say that this whole cohort, 80% had a university degree.

Emma: Okay.

Jerilynn: So, it was a pretty well-educated group of women. But those were the only things we could come up with, that related to ovulation, it explained only 17% of the variance. 

So, it's been a puzzle to try to sort out what is related to ovulation disturbances, and we've come down to using the data from the diary and women's self-reported health to create a kind of resilience-like scale. And it seems like those who are more resilient, and this includes things like perseverance, equanimity, feeling calm, self-reliance, a sense of meaning in life, and also a feeling of being okay to be alone, okay with yourself, if you're by yourself, those kinds of things are associated with resilience. And the women who were normally ovulatory since I presented this we've discovered have higher resilience.

Emma: Yeah. I find that fascinating because COVID was the ultimate stress for many people and a time of great uncertainty.

Jerilynn: Oh, yeah.

Emma: And when you said initially that it's an adaptive and protective mechanism of the body, but to find that 63% of women were having these non-ovulatory cycles during COVID in your research, I think it explains a lot to us as clinicians of why women were saying that their cycles were a little all over the place.

Jerilynn: Yeah. Yeah, exactly. It's just the beginning of trying to understand what's going on. I'm hoping that it will catch the attention of the powers that be so we stop ignoring progesterone and stop ignoring ovulation.

Emma: Yeah. Ultimately, COVID was a big stress test for everyone, and your study was the first piece of evidence that ovulatory disturbances without cycle length changes can be associated with stresses. And this was sort of put under the microscope during a pandemic, but I guess the silver lining is, hopefully, the insights and information from this will come to light and help in other ways.

Jerilynn: I hope so.

Emma: Yeah.

Jerilynn: Yes, because it's too important to ignore.

Emma: Yes. Absolutely. What about treatments? What kind of treatments are available for ovulatory disturbances?

Jerilynn: Okay. That's again something that requires collaboration between a woman and her healthcare provider. So, understanding for some person, it's going to be a conflict with their boss. For another person, it's going to be an unruly child. For another person, it's going to be the worry about money. In other words, each person is likely to know for herself what it is that she's susceptible...what's really stressful for her. And so that's one of the things that keeping the menstrual cycle diary does is that it helps her to sort out for herself how she reacts to various things...

Emma: Good point.

Jerilynn: ...both physiologically and emotionally. And so, once she knows that, you can help her to have better nutrition if she's really stressed with a due date or something and doesn't eat normally, or if she's getting up at night because she's worried about something, someone to talk with about it, ideally, also, some kind of friend, community support. And then if you've worked on that, nutrition, emotion, illness, whatever those variables, then if it's still not becoming right, then you can use cyclic progesterone as a way of replacing the luteal phase until that woman's cycle returns to normal.

Emma: Okay. Because this I find very interesting because you have coined the term ‘cyclic progesterone therapy.’ So, what is this exactly? I know there's a lot of research on micronised progesterone, for example, for IVF or birth outcomes, but what is this? How is it used? How do women access it?

Jerilynn: Okay. So, first of all, it's prescribed and it's ideally oral micronised progesterone, which usually comes in little round balls, each 100 milligrams. I guess now there's a 200-milligram one. And the dose that keeps the progesterone in the luteal phase range for 24 hours is 300 milligrams, but you can only take it at bedtime, so once every 24 hours. So, you need a higher dose than you would if you could give it twice a day or whatever. So, 300 milligrams taken on the way to sleep, basically, starting on cycle day 14 if the person has a 28 to 30-something-day cycle, or day 12 if their cycle is shorter, and repeating.

And I've spent many years trying to refine that because some women will have bleeding early. They start taking it, and on nine days into taking it, they get their period. So, what happens normally if you don't understand what you're trying to do here, is that when most stop their pill, say, "Oh, my period came now." But in fact, what you need to do is continue the full 14 days, but start the next cycle based on when the flow began. So, in other words, you would start taking the next cycle of progesterone earlier than you would've before, 14 days after the beginning of flow. So, you might be only off the progesterone for eight days, say.

Emma: Okay.

Jerilynn: And then, see what happens when you have bleeding while you're taking progesterone is that your oestrogen was too high, or the lining of the uterus was too thick. The progesterone that you're taking now is a normal dose, but it's trying to catch up for several months before that when it wasn't normal.

Emma: Okay. So, a woman would take the dose of 300 milligrams in the evening for a 14-day period of time.

Jerilynn: Right.

Emma: And that simulates or supports the progesterone, that then will help to regulate and normalise everything.

Jerilynn: Yeah. It's giving her back the progesterone her body's not able to make right now. And I actually think, though I can't prove it, I did ask a study before and I tried to, but not enough people. I think it talks back to the hypothalamus and teaches the hypothalamus that's gotten kind of confused to be cyclic again.

Emma: Yes. It's this cyclic pattern that we're trying to support that natural cyclic pattern.

How long can a woman use micronised progesterone for?

Jerilynn: I always say as long as she needs it.

Emma: Okay.

Jerilynn: So, for example, we've done a randomised controlled trial that shows that it improves and effectively treats hot flushes in menopausal women. We've also done a trial that shows that it effectively treats night sweats in perimenopausal women.

Emma: Oh, okay.

Jerilynn: And in both groups, it improves sleep. And in perimenopause, it also improves their ability to cope or their sense of how much disturbed they are by perimenopause. And did not cause depression. We did a depression scale and it did not increase depression. No difference from placebo.

Emma: Okay. Fantastic. So, this is a very fantastic therapy option for many women, not just regular menstruating, but for almost many life stages, this can be a fantastic therapy. And if it's building on resilience, then that then feeds back into the data coming from your COVID research on improving that resilience scale.

Jerilynn: Mm-hmm. So, I should say very clearly that the evidence that it causes serious harm as a drug, which it is, is just non-existent. It doesn't cause clots, as different from both progestins and also from oestrogen. It doesn't make migraines worse. You can use it, in fact, to treat migraines. It doesn't increase breast cancer. It prevents endometrial cancer. So, the things that women normally worry about. We don't know for sure because it hasn't been studied very much in the brain, but it is a calming hormone in the brain, and it may very well decrease the risks for things like dementia, and it may very well decrease the risk for heart attack. We don't know. We just don't know.

Emma: Yeah. I have to say clinically, I have seen it do some fantastic things for women, not just their physical symptoms, but also their mental and emotional health. I've really seen an impact on that side of things. Yeah. 

I would like to just finish up with the fact that on your website you have a series of daily diaries. These are fantastic clinical tools for people out there, so thank you so much for creating those. Are there any other resources you could share with us? Any apps that you actually do think are good? Any other resources in this space?

Jerilynn: I would say, in general that - and I haven't explored the recent Clue app, so I can't speak to that - but most of the apps are not adequately scientific. We've got some really strange data like cycle lengths and ovulation getting better during COVID that were done with the Natural Cycles app using the BBT. And that just muddies the water. If you don't have an accurate tool, how can you get accurate data?

Emma: Yes.

Jerilynn: So, I would not recommend using an app if you don't know for sure that it's accurate.

Emma: Yes. I would agree with you because I can't tell you how many times I've been in clinic with the patient and I ask her, "When do you ovulate?" And she pulls out her phone, she says, "Oh, my app tells me on this day." And I said, "But what else happens around that time? What happens in your body?" So, taking it back to that level I think is critical. It's absolutely critical. 

Any final last points for us, Jerilynn? There's so much information we have already talked about, but any final thoughts?

Jerilynn: I just think that each woman has the tools that she can use free from the CeMCOR website to assess her own, keep the diary herself, keep a morning temperature record as long as she's not working night shifts part of the time, and to see for herself if she's ovulating normally.

Emma: Yeah.

Jerilynn: It's part of self-knowledge. And with self-knowledge, comes self-confidence and that resilience we're talking about.

Emma: Yes. Very, very timely and good point. Thank you so much for joining us today, Jerilynn. I've got some key points that I've taken away. 
First and foremost, a regular normal-length cycle does not guarantee a normal ovulation. Also, there are four different reproductive anomalies, amenorrhea, oligomenorrhea, normal cycle and ovulation, and normal cycle with a short luteal phase, but essentially, all of them are possibly and most likely an adaptive response in the face of stressors, and that treatment absolutely needs to involve addressing those stressors. But we also have cyclic oral micronised progesterone as a treatment option for women as well, which I think is very welcome news.

Jerilynn: I'm glad and thank you.

Emma: It's our pleasure. 

Thank you everyone for listening today. Don't forget, you can find all the show notes, transcripts, and other resources from today's episode on the fx Medicine website, fxmedicine.com.au. I'm Emma Sutherland, thanks for joining us, we'll see you next time. 


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