7.3 Menopausal Psychosis and Hormone Therapy: Basics of Menopause and Menopausal Psychosis

[00:00:00] Here, Dr. Wood kicks us off by explaining what perimenopausal psychosis is, then Dr. Gratter

[00:00:06] gives us the OB/GYN perspective on what menopause is, what women can expect during this transition,

[00:00:13] and talks about some of the basic hormones that fluctuate.

[00:00:17] Before we dive in, I want to give you all a little more historical background about hormones,

[00:00:22] and the evolution of HRT or hormone replacement therapy as a medical treatment.

[00:00:41] So in the last decade of the 1800s, a British oncology surgeon George Beatson successfully

[00:00:48] treated two cases of breast cancer by removing his patient's ovaries.

[00:00:53] In 1906, it was discovered that ovaries produced estrogen, but it wasn't until 1929 near the

[00:01:01] onset of the Great Depression that US researchers Edgar Allen and Edward Doisey successfully

[00:01:08] isolated estrogen.

[00:01:10] Just four years later, fellow Americans Willard Allen and George Washington Corner, at University

[00:01:16] of Rochester in Minnesota, discovered another pivotal hormone, progesterone.

[00:01:22] Estrogen and progesterone are the two most significant fluctuating hormones in the roughly

[00:01:27] month-long female menstrual cycle, and also undergo major variations during pregnancy,

[00:01:34] postpartum, and menopause.

[00:01:36] In 1931, prominent American gynecologist Robert Frank published "The Hormonal Causes of Premenstrual

[00:01:44] Tension", hypothesizing that fluid retention from excess estrogen caused headaches and

[00:01:50] bloating around the bleeding phase of the menstrual cycle, but these symptoms did not

[00:01:55] improve with estrogen reduction therapy.

[00:01:58] Around a decade later, building off of Frank's work, a pregnant 32-year-old British medical

[00:02:04] student, Katarina Dalton, began consulting with endocrinologist Raymond Green after realizing

[00:02:11] her monthly migraines had disappeared with her pregnancy.

[00:02:15] Dalton subsequently dedicated her life's work to investigating the effects of progesterone

[00:02:20] on physical and mental symptoms caused by hormonal fluctuations, and her and Green coined

[00:02:27] the term "premenstrual syndrome" or PMS in 1953.

[00:02:33] She opened a PMS clinic in London in 1957 and directed it for 30 years.

[00:02:40] She challenged the use of high doses of vitamin B6, or pyridoxine, which was the standard

[00:02:46] of care for treating PMS at the time due to linking B6 with sensory neuropathy, and she

[00:02:54] helped countless patients get normal sensation back.

[00:02:58] She also worked with incarcerated females and discovered a correlation between when they

[00:03:02] committed their crimes and the proximity to menstruation, testifying as an expert witness

[00:03:09] in dozens of legal cases.

[00:03:11] As Dr. Greider educated me on, as female gynecologist age, they're in a unique position

[00:03:17] of pairing their personal experiences with their clinical experiences, and later in Dalton's

[00:03:23] life, she worked more with using progesterone and menopause to help alleviate symptoms.

[00:03:30] Some believe her work on hormone replacement therapy was suppressed in the 1980s and 1990s,

[00:03:36] which coincidentally coincides with the timing of many SSRI antidepressants going on patent

[00:03:43] and becoming first-line for treating menopausal psychiatric symptoms during this time.

[00:03:49] As Dr. Dalton was gaining influence for her work on PMS and monthly cycles, in 1963 a

[00:03:56] Brooklyn gynecologist Robert Wilson and his wife, Thalba, published a paper in the Journal

[00:04:02] of the American Geriatric Society urging physicians to use hormones to treat menopause, stating

[00:04:09] that untreated menopause robbed women of their femininity and ruined their quality of life.

[00:04:15] In 1966, Dr. Wilson published a best-selling book titled "Feminine Forever" that split

[00:04:23] the feminist movement, but overall popularized HRT, now just called HT, or hormones.

[00:04:29] In 1975, it became apparent that unopposed estrogen increased the risk of endometrial cancer, leading to a brief reduction in HRT use. But within a few years, it was discovered that combining estrogen with progesterone decreased the risk of endometrial cancer and revitalized the use of HRT.

[00:04:52] In 1988, HRT gained FDA approval for a huge new indication, osteoporosis prevention, a common effect of diminishing estrogen production and menopause, making HRT more popular than ever before.

[00:05:08] In 1991, the NIH launched the Women's Health Initiative study to better understand the safety and efficacy of HRT during menopause. We'll talk more about its flaws and negative impact on HRT use more in the next segment.

[00:05:25] Before we move on, I do want to provide a couple of relevant statistics to emphasize the importance of this topic. While there isn't great data on menopause, it's generally associated with a roughly 20% risk of experiencing psychiatric symptoms.

[00:05:41] In a period with more data, occurring prior to menopause is postpartum, when many women have major hormonal fluctuations and risk getting depressed or even psychotic, in the 1-6 week period following delivery of a child.

[00:05:56] In the general population, mom's risk of experiencing mild subclinical depressive symptoms, or the baby blues, is as high as 75%, while clinical postpartum depression occurs in 10-20% of women, and psychosis in 0.2%, or 2 out of every thousand births.

[00:06:18] Suicide is the leading cause of maternal death during the postpartum period, and in women experiencing postpartum psychosis, about 5% will attempt suicide via much more lethal means than the general population, and 4% will actually commit infanticide, killing their baby.

[00:06:39] Prior to the advent of ECT, or shock therapy, in the early 1940s, which is an effective and safe treatment for pregnant and/or postpartum women with severe symptoms, one study following 39 women with postpartum psychosis showed that 9 out of 14 women with the condition died during psychiatric admissions compared to only one death in 23 women after ECT was introduced.

[00:07:08] Look, the thing is, the symptoms women experience during these hormonal transition periods in their lives can be extremely severe and even life threatening.

[00:07:21] The goal of discussing this topic is not to convince any patient or provider to take or prescribe hormone therapy, it is to present information, evidence, and provide professional discourse on the topic, so ultimately, women can make their own decisions about what they do with their own bodies and brains.

[00:07:48] What is perimenopausal psychosis?

[00:07:52] Well, by very broad psychiatrist answer to what is menopause, the years towards the end of a woman's reproductive life in which a lot of hormone changes are starting to happen, menses are becoming less regular, and eventually that culminates in a final menstrual period, and you are considered to be post-menopausal about 12 months after the last menses.

[00:08:15] During this time, we know that the body is going through a lot of different changes, specifically endocrine changes, hormonal changes, that can be experienced in a lot of different ways, so we have the physical, vasomotor symptoms, we have effects on things like anxiety, mood, thought processes.

[00:08:32] When a person develops depressive symptoms around the period leading up to menopause, typically in that transition phase, depressive symptoms can look like low mood, sleep changes, reduced appetite or increased appetite, difficulty motivating yourself, low energy, decreased interest in things, and even suicidal thoughts.

[00:08:54] thoughts, a woman who might be experiencing perimenopausal depression, that might be her first

[00:09:00] ever time having a mood episode like that. It could be brand new or it could be someone who has a

[00:09:05] known history of depression or bipolar disorder who's now having a new episode in the setting of

[00:09:09] this menopausal transition. And as far as perimenopausal psychosis goes that can look like a variety of

[00:09:16] things but sometimes delusions, hallucinations, changes in thinking like not being in touch with

[00:09:23] reality and it really can affect people's functioning in a pretty severe way. And again with perimenopausal

[00:09:29] psychosis that can be brand new, first time episode never had any kind of psychosis before,

[00:09:35] or it may be in the case of someone who has a known diagnosis of schizophrenia or bipolar that

[00:09:39] they do have a new episode around the time of the menopausal transition. One thing I didn't realize

[00:09:44] of course my man brain is just like okay well menopause yeah it just happens right? No I mean

[00:09:51] it can be a pretty lengthy transition for several years. One of the questions that I've always had

[00:09:58] is does the length of that transitional period does that matter? AKA does the change in hormone

[00:10:06] levels happening over a more rapid timeframe? Does that lead to more risk? I don't think I really

[00:10:12] could find a great answer to that. Yeah we'd be there. The one thing I did find a pretty consistent

[00:10:19] answer to is the longer a woman has in childbearing age from the time they have their first period to

[00:10:27] the time they have their last period, that is protective against these conditions. So if you had

[00:10:33] 35 years of childbearing age compared to somebody who only had 20 or 25 then you would have a lower

[00:10:42] risk of developing depression or any psychotic symptoms. That transition period when the hormones

[00:10:48] are fluctuating and we know that hormones specifically estrogen doesn't just like steadily decrease in

[00:10:54] the perimenopausal transition but it can go up and down. It's not always consistent with time or what

[00:11:00] we might expect. Something about the change in the levels, the drop, the withdrawal if you will that

[00:11:05] probably has more of an effect on these symptoms than just the pure absence of it. You and I have

[00:11:10] described a condition that affects a woman's memory that affects a woman's insight and if those

[00:11:17] are affected by this condition and postpartum depression we may be evaluating perimenopausal

[00:11:24] women and they may not be able to reliably report what happened after the birth of their children.

[00:11:32] There's the kind of I'd almost reporting bias if you will by the default of the nature of what

[00:11:39] we're asking them like yes insight and memory was affected so they won't necessarily know.

[00:11:43] A hundred years ago this wasn't a problem that too many women would ever get to and if it's

[00:11:49] like every other health problem or most other health problems that is affected by environmental

[00:11:55] factors, adverse childhood events, socioeconomic status, stress, then the ones who would be affected

[00:12:05] probably weren't going to live as long of a lifespan as some of the others that wouldn't necessarily

[00:12:11] be affected. That's interesting yeah like they're maybe selected out in a way so we just didn't see

[00:12:16] it. And to your point of women not getting the medical or psychiatric attention at that age

[00:12:23] that they deserve like okay well we're gonna let them just go right they're not of value but in the

[00:12:30] last 50 years I mean the average lifespan for a woman is now 80 you're talking about women who have

[00:12:38] 20 to 50 years of life left now my grandma's 93 and she still plays golf.

[00:12:43] What would you say is the typical or most common first sign of menopause?

[00:12:53] Let me back up just a little bit and just define menopause. Menopause is the phase of life for a

[00:12:58] woman where her ovaries shut down and stop making eggs so it signifies the end of her reproductive

[00:13:07] years so she can't get pregnant. And it really is a transition time so we consider somebody

[00:13:14] through menopause when they've been a year without a period because their ovaries are shut down then

[00:13:20] we say they're post-menopausal and then that starts for our life expectancy now that whole

[00:13:26] third of your life, but that perimals...

[00:13:29] Apostle time frame is like puberty number two and for different women for different people it's different links and different

[00:13:37] Saverities just like puberty number one is many women the big things that we're searching for the magic bullet is

[00:13:42] Hormones youth libido and weight loss. Those are the big ones and we'll pay millions and billions of bucks

[00:13:48] They don't really want to hear what the issue is and what the answer is so they get sucked into some of these

[00:13:56] Pretty sales pitches of you know check a hormone here and there and compare and start chasing your tail with that

[00:14:02] But where there's smoke, there's fire

[00:14:05] So the problem that's causing women the angst is the hormones up and the hormones down and you can do hormone levels every few days

[00:14:12] And they're gonna be drastically different and that's the problem

[00:14:14] And it doesn't necessarily mean that the hormones are not right because that's

[00:14:20] Normal for where you are for your phase of life

[00:14:23] But how it makes you feel doesn't feel right to you. And so the hormone swings are what caused many people the angst

[00:14:30] So many women start with some period changes and for most people that really gets going in the early 40s

[00:14:38] You're gonna start noticing that it feels like your hormones are different

[00:14:41] It doesn't mean you're crazy, but there are changes that are happening more PMS more acne more breast tenderness

[00:14:48] Hot flashes and night sweats particularly the week around the period for women who don't have periods because of either a hysterectomy or an ablation or something like that

[00:14:58] Then it's a little bit different if you're technically gonna define where they are for menopause

[00:15:03] It takes consecutive lab work a year apart

[00:15:05] But I don't go checking a bunch of labs because if a woman is having a cycle and I know where she isn't her cycle

[00:15:13] I can either tell you if her hormones are gonna be high or low or at medium range

[00:15:17] I don't necessarily need to check a lab to know that

[00:15:20] I'm so glad you brought that up because I was gonna ask if the hormonal changes always correlate with the symptoms

[00:15:28] Sometimes we go against common sense just if we have a lab value that doesn't match up as a psychiatrist with

[00:15:35] six weeks of OBGYN service experience and a

[00:15:40] comparatively very poor understanding of hormonal feedback loops once I knew that the hypothalamus secrete's

[00:15:47] gonadotropin releasing hormone which stimulates the pituitary to release FSH and LH or

[00:15:55] follicle stimulating and luteinizing hormone

[00:15:58] Which then feeds down to the ovaries to stimulate estrogen

[00:16:02] Production and progesterone gets in there somewhere and oxytocin's another one

[00:16:07] Can you give me a third-year medical student level refresher on the major hormones that are involved in the female menstrual cycle and menopause?

[00:16:16] Yeah in your reproductive years your brain tells your ovaries to get to work

[00:16:21] estrogen production in the ovaries

[00:16:24] causes the lining of the uterus to build up and then when you ovulate and

[00:16:30] We haven't really cracked that code. I can't really tell you what causes ovulation, but when you ovulate you release progesterone hormone

[00:16:38] That stabilizes that lining of the uterus. So if that egg that's ovulated gets fertilized

[00:16:43] then there is a

[00:16:46] thickened uterine lining for that fertilized egg to implant if a woman doesn't get pregnant that cycle the

[00:16:52] Hormone levels drop and then everything that was built up in the lining of the uterus sheds off and so that your menstrual cycle

[00:16:58] So it builds up sheds off and builds up and it sheds off

[00:17:00] one of the early things that start with the menopause transition is that women are not ovulating regularly

[00:17:08] They're still making estrogen. They're just not making the progesterone hormone because they're not ovulating

[00:17:13] So they may have longer periods of time between their periods and their periods make it heavier and make it more irregular

[00:17:19] as you get a little bit more into menopause transition your ovaries start shutting down so your ovaries aren't making the estrogen or the

[00:17:26] progesterone and so the lining isn't thickened enough periods sometimes are getting lighter and then just when you start getting the hot flashes and night sweats

[00:17:34] During those periods of time that you're missing a period. My basic understanding is that low estrogen

[00:17:40] can lead women to feel depressed and

[00:17:43] have poor

[00:17:45] cognitive function in some areas, but like you said, it's the swinging changes in the level of estrogen not any

[00:17:52] Specific number. I know it's not just mood, but can you talk about the correlation between hormone levels?

[00:17:59] and mood symptoms or going beyond that psychotic symptoms. You know a lot of the physical changes

[00:18:06] that happen when your estrogen levels drop gives you like the headaches, the hot flashes in the

[00:18:12] night sweats, some sleep disturbance. When you are going without proper sleep just night after night,

[00:18:19] that builds up and then people can't focus and then they can't concentrate as well. Their

[00:18:24] memory and those kinds of things are not as good. Progesterone is typically for us known as the

[00:18:31] PMS hormone. Many people in the time right before a period which is that pre-menstrual time,

[00:18:39] they have the increase in their progesterone levels. With that a lot of people get the

[00:18:43] irritability and they're just more cranky and then estrogen is your feel-good hormone and around

[00:18:48] the time of ovulation, the time that you feel the best about yourself, you feel the most receptive

[00:18:54] to your partner from an evolutionary standpoint. Your estrogen levels are high, your testosterone

[00:19:00] is at a better level at that point and then after ovulation the progesterone takes over and then

[00:19:07] it's more rare. You know we see that in the animal world. If you find animal when they're

[00:19:13] ovulating, the only time that they're receptive sexually to their partner and then after that

[00:19:18] they will fight them off. It's interesting you mentioned that because as humans we're very unique

[00:19:23] because we have this big very developed frontal lobe that gives us awareness and consciousness

[00:19:30] levels that other animals don't experience but we also have a mind that operates a lot more like

[00:19:37] in animals and we have thoughts and emotional reactions to things that seem to just come on

[00:19:44] without warning and with the cases that I've seen these women in this transition period it's almost

[00:19:51] like they have this fear and anxiety that they're not going to be able to protect their families or

[00:19:57] support their families and it's this idea that gets into their psyche and it's almost like they

[00:20:04] have a thought about a possibility and a worry. Something that is very animalistically survival

[00:20:11] based. You know our thoughts go through our frontal lobe to then decide whether or not to act

[00:20:17] but it almost seems to bypass that system. I would bring in the patient's family every other day.

[00:20:24] Here they are they're not dead but not an hour or two after they leave back to being convinced

[00:20:30] my family has been irreparably harmed and they're no longer with us. That's interesting that's not

[00:20:36] what I see on a day-to-day basis at all or on really even an infrequent basis but my answer to that

[00:20:44] is if anybody has anything that they think is related to a period or menopause then we replace

[00:20:51] those hormones or we level out those hormones and we see if it helps. Honestly I thought earlier when

[00:20:56] you were talking about your experiences and how you haven't really seen a psychosis but I've seen

[00:21:02] several in a very limited career to this point it's sad. People don't think huh this seems like

[00:21:09] it could be harmonally related and we're pursuing measures like antipsychotics, SSRIs, ECT they just

[00:21:18] don't impact the problem in a clinically significant way. Somebody get this guy some help.

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[00:22:22] provider or other health care provider if seeking medical advice diagnosis or treatment or put

[00:22:26] more simply you need help like this guy call your own doctor