HoldsUp

DavidPerlmutterMD · 2021-11-15 · Stephanie Estima, David Perlmutter (host)

Make Your Menstrual Cycle Your Superpower - with Dr. Estima | The Empowering Neurologist EP. 137

24 research-tied claims examined: 3 overstated 4 context 15 supported 2 unverified

15

Supported by research

0:00:30David Perlmutter (host)supportedmoderate

Medication development and testing have historically been male-centric despite medications frequently being prescribed to women.

"We look at medications, for example, and recognize that while medications are often prescribed for women, their development and testing really is male-centric, and that is inappropriate." (said at 0:00:30)

Historical drug development and clinical trial testing have well-documented male bias and female underrepresentation across multiple therapeutic areas, despite high prescription rates among women. Systematic evaluations demonstrate that while women make up a substantial proportion of patients requiring and receiving medications (such as cardiovascular drugs and antibiotics), they have historically been underrepresented in pivotal clinical trials, often resulting in limited sex-stratified safety and dosing data and a higher incidence of adverse drug reactions.

0:12:13Stephanie Estimasupportedmoderate

In the days leading up to menstruation, a sharp drop in estrogen and progesterone cuts off blood supply to the endometrial lining, causing tissue ischemia and subsequent shedding.

"here, you know, in the couple of days leading up to your cycle, we see a pronounced drop in progesterone, a pronounced drop in estrogen. And so what's happening now is that the endometrial lining, which was building up expecting that fertilized egg, is now becoming ischemic. There's no oxygen that is now being relayed to it, the blood supply is being cut off, and then it dies. Those cells die, and that's what your period is: it's the shedding of that endometrial lining." (said at 0:12:13)

The speaker accurately describes the classical physiological mechanism of menstruation. In the late luteal phase, the regression of the corpus luteum causes a steep decline in circulating estradiol and progesterone. This withdrawal of steroid support triggers intense vasoconstriction and vasospasm of the endometrial spiral arterioles, causing severe ischemia, local hypoxia, and tissue breakdown in the functional layer of the endometrium, which culminates in menstrual shedding and bleeding.

0:17:34Stephanie Estimasupportedhigh

Early perimenopause often features a shortening of the menstrual cycle, whereas late perimenopause is characterized by lengthened cycles and frequent anovulatory cycles.

"As we begin to move into perimenopause, those early stages of perimenopause, you may see a shortening of your cycle. So what once was 29 maybe now is 27. And then of course, in later perimenopause, we see that extension; we see, you know, many, many cycles, many anovulatory cycles, where they will go months without a period, for example." (said at 0:17:34)

The speaker accurately describes the characteristic menstrual patterns across the stages of perimenopause. According to the Stages of Reproductive Aging Workshop (STRAW + 10) criteria and longitudinal cohort studies of reproductive aging, the early transition is often marked by cycle variability and shortening (primarily due to an accelerated follicular phase), whereas the late transition is defined by skipped cycles (amenorrhea lasting 60 days or more) and an increased frequency of anovulatory cycles.

0:20:00Stephanie Estimasupportedhigh

During the bleed week of the menstrual cycle, estrogen and progesterone levels are low while follicle-stimulating hormone stimulates the developing follicle.

"So in that bleed week, as I mentioned, when we look at the hormonal composition of the female during that week, typically everything is quite low. So we see estrogen is very low, progesterone is not in the picture at all. The only hormone that we really do see that's working to hold down the fort, if you will, is follicle-stimulating hormone, which is doing just what it says: it is stimulating the follicle which houses the egg." (said at 0:20:00)

During menstruation (the early follicular phase), circulating levels of estrogen and progesterone are at their basal nadir following the regression of the corpus luteum. In response to the withdrawal of these sex steroids, pituitary secretion of follicle-stimulating hormone (FSH) rises across the luteal-follicular transition to stimulate the recruitment and growth of a cohort of ovarian antral follicles.

0:23:38Stephanie Estimasupportedhigh

Males have between 10 and 80 times more testosterone than females.

"there's, you know, 10 to 80 times more testosterone in a male versus a female" (said at 0:23:38)

The claim is supported. Reference intervals established via mass spectrometry (LC-MS/MS) show that circulating total testosterone levels in healthy adult males typically range from approximately 10 to 35 nmol/L (~300 to 1,000 ng/dL), whereas in adult females they range from approximately 0.4 to 2.0 nmol/L (~10 to 60 ng/dL). On average, men have about 15- to 20-fold higher circulating testosterone than women, and comparing reference boundaries across adult populations yields differences spanning approximately 10-fold to over 80-fold.

0:26:45Stephanie Estimasupportedhigh

Luteinizing hormone surge triggers the release of the egg from the ovarian follicle during ovulation.

"So ovulation is, you know, the release of the egg from the follicle. That is under, again, the influence of luteinizing hormone, which we haven't mentioned yet... And that's what luteinizing hormone does, right? Comes in kind of out of the blue and then helps with that release of the egg from the follicle." (said at 0:26:45)

The speaker's statement accurately reflects established reproductive endocrinology. Ovulation is triggered by the midcycle surge of luteinizing hormone (LH) released from the anterior pituitary gland, which activates downstream signaling cascades, inflammatory mediators, extracellular matrix remodeling, and proteolytic degradation of the follicle wall, culminating in follicular rupture and the release of the oocyte (egg).

0:27:30Stephanie Estimasupportedhigh

A released human ovum remains viable for fertilization for approximately 24 to 36 hours (at most 48 hours).

"And you are really only—one one thing to really note is that egg is only really viable for 24 hours, maybe 36, you know... So egg is viable 36 hours, let's call it 48 if we're being generous." (said at 0:27:30)

Human reproductive biology and epidemiological studies of the fertile window establish that a released human ovum has a functional lifespan of approximately 12 to 24 hours (rarely up to 24-48 hours) post-ovulation. Epidemiological models of the 6-day fertile window (the 5 days preceding ovulation plus the day of ovulation) demonstrate that the probability of conception drops rapidly to near zero the day after ovulation, reflecting the short 12-24 hour window of oocyte viability. The speaker's statement that an egg is viable for 24 hours, maybe 36 to 48 hours at most, accurately reflects the upper physiological limits recognized in reproductive physiology.

0:28:55Stephanie Estimasupportedhigh

Following ovulation, the ovarian follicle transforms into the corpus luteum, which secretes progesterone to thicken the endometrial lining.

"And then we move into the secretory phase or the luteal phase. So now the follicle, we refer to it now as the corpus luteum, and the corpus luteum is now going to be secreting progesterone, so pro-gestation, pro-pregnancy hormone, and that is going to help to amplify and to build out this endometrial lining" (said at 0:28:55)

The speaker's description of female reproductive endocrinology is well-established textbook physiology. Following ovulation, the remaining ruptured ovarian follicle luteinizes to form the corpus luteum, which secretes high levels of progesterone during the luteal (secretory) phase. This progesterone acts on the estrogen-primed endometrium to drive secretory transformation, vascularization, stromal decidualization, and glandular maturation in preparation for embryo implantation.

  • supports: The normal menstrual cycle in women. (Animal reproduction science 2011) · cited 441x in the literature
    "The corpus luteum secretes progesterone, oestradiol and inhibin A in response to LH pulses, and reaches its peak in terms of size, secretions, and vascularization 6-7 days after ovulation. Luteal regression is passive and independent of the uterus, but can be prevented by hCG, the luteotrophic signal from the trophoblast, from 8 days after conception. Reductions in systemic steroid and protein hormone concentrations may be responsible for the FSH rise characteristic of premenopausal women. The functional layer of the endometrium shows steroid hormone-dependent proliferation, differentiation, and shedding in the absence of the trophoblast." (abstract, results, passage verified)
    pubmedfull study (doi)
  • supports: Luteal phase support in assisted reproductive technology. (Nature reviews. Endocrinology 2024) · cited 56x in the literature
    "Specifically, we outline the physiological luteal phase, which is regulated by progesterone from the corpus luteum, and evaluate how it is altered by the supraphysiological ovarian stimulation used during IVF. Additionally, we describe the effects of the hormonal triggers used to mature oocytes on the degree of luteal phase support required. We explain the histological transformation of the endometrium during the luteal phase and evaluate markers of endometrial receptivity that attempt to identify the 'window of implantation'." (abstract, conclusions, passage verified)
    pubmedfull study (doi)
0:29:30Stephanie Estimasupportedhigh

In a 28-day menstrual cycle, progesterone levels reach their peak around day 21 or 22.

"we will see progesterone reach uh the peak around day 21, 22 if we're talking about a 28-day cycle." (said at 0:29:30)

In a classic 28-day menstrual cycle with ovulation occurring around day 14, progesterone secreted by the corpus luteum reaches its peak during the mid-luteal phase, approximately 7 to 8 days post-ovulation (around day 21 to 22), before declining prior to menses if fertilization does not occur.

0:18:05Stephanie Estimasupportedmoderate

Menstrual blood clots that are the size of a quarter or larger are considered abnormal and indicative of excessive bleeding, whereas dime-sized clots can be within the normal physiological range.

"dime-sized clots are, you know, some of those are considered within the scope of normal, but if they're sort of a quarter size or they're larger, or they're all the time, or your flow is so heavy as I've previously shared, where I was, you know, needing to bring a change of clothes, then that would be considered excessive." (said at 0:18:05)

Clinical hematology and gynecology guidelines recognize menstrual blood clots measuring a quarter in diameter (approximately 1 inch or 2.5 cm) or larger as a key clinical predictor of heavy menstrual bleeding (menorrhagia) or underlying bleeding disorders, whereas smaller clots (such as dime-sized) can occur within normal physiological limits.

0:29:16Stephanie Estimasupportedhigh

Following ovulation, estrogen levels experience a brief decrease before rising again and remaining elevated throughout the luteal phase.

"So in week three, we see a drop in estrogen, and then she comes right back up, and then for the next, you know, call it week and a half to two weeks, we see that sustained release of estrogen." (said at 0:29:16)

The claim accurately describes normal human menstrual cycle physiology. Circulating estradiol reaches an initial peak immediately prior to ovulation, drops sharply in the early post-ovulatory period, and then rises again during the luteal phase as it is synthesized and secreted by the corpus luteum alongside progesterone, producing a secondary elevation during the mid-luteal phase before declining prior to menses if fertilization does not occur.

0:30:21Stephanie Estimasupportedmoderate

During the luteal phase of the menstrual cycle, progesterone elevation causes increased water retention, abdominal bloating, irregular bowel movements, disturbed sleep, and increased basal body temperature.

"So you might feel that it's, you know, it's harder to, you know, get your rings on, you may feel like you're retaining more water, you might feel more distended and bloated after, you know, a meal, your bowel movements are not as regular, your sleep is now becoming more disturbed. And this is all under the influence of progesterone, and you're generally your body temperature is also lifting up as well." (said at 0:30:21)

The speaker's statements regarding the physiological effects occurring during the luteal phase of the menstrual cycle under the influence of elevated progesterone are supported by published literature. During the progesterone-dominant luteal phase, progesterone promotes heat conservation leading to a well-documented increase in basal body temperature. Progesterone also exerts a relaxing effect on gastrointestinal smooth muscle, prolonging gastrointestinal transit time and leading to irregular bowel movements (such as constipation) and increased abdominal bloating and distension.

0:30:45Stephanie Estimasupportedhigh

The drop in both estrogen and progesterone prior to menstruation triggers premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) symptoms, including breast tenderness, irritability, and emotional distress.

"And then there's that, you know, that that phase that I talked about just briefly around having progesterone and estrogen drop once, you know, your body's like, "Okay, it's not here, the egg is not fertilized, we have to get rid of it." And this is often when a lot of women who complain about premenstrual syndrome or even more severely PMDD, this is where we start to see um a lot of like the tender, swollen breasts, very like very irritable, crying, emotional, feeling very emotional." (said at 0:30:45)

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are characterized by physical symptoms (such as breast tenderness and swelling) and psychological symptoms (such as irritability, mood swings, and emotional distress) that arise during the luteal phase of the menstrual cycle—coinciding with the post-ovulatory rise and subsequent decline in estrogen and progesterone prior to menstruation—and remit following menses. Clinical and mechanistic studies demonstrate that these symptoms are driven by an underlying sensitivity to normal physiological fluctuations and withdrawal of ovarian sex steroids.

0:48:48Stephanie Estimasupportedmoderate

Berberine mimics the metabolic effects of metformin, and taking 1,500 mg daily divided into three 500 mg doses right before meals blunts postprandial blood glucose spikes.

"So berberine is a really interesting uh natural uh compound that has been shown to mimic uh some of the benefits that metformin um—which is a drug uh for those of you listening that are not familiar, is usually is a drug that's been around for like 80 years, very common in type 2 diabetes to help reduce blood sugar. So berberine, you know, taking 1,500 mg, well, divided into three doses—so 500 mg thrice daily and right before meals—has also been shown to blunt um a very high postprandial, or post-meal, uh glucose spike in the blood." (said at 0:48:48)

Clinical trials and systematic reviews support that berberine exerts metabolic effects comparable to metformin in type 2 diabetes, including lowering fasting and postprandial blood glucose levels. In a foundational randomized trial comparing berberine (0.5 g three times daily) to metformin (0.5 g three times daily) in patients with type 2 diabetes, berberine produced glycemic reductions similar to metformin and significantly lowered 2-hour postprandial blood glucose. Subsequent meta-analyses of randomized controlled trials have confirmed that berberine significantly reduces postprandial plasma glucose, fasting blood glucose, and HbA1c.

0:48:48Stephanie Estimasupportedhigh

Metformin is a type 2 diabetes medication that has been in clinical use for approximately 80 years to lower blood sugar.

"metformin um—which is a drug uh for those of you listening that are not familiar, is usually is a drug that's been around for like 80 years, very common in type 2 diabetes to help reduce blood sugar." (said at 0:48:48)

Metformin is a standard, widely prescribed first-line medication for type 2 diabetes used to reduce blood glucose levels. Chemically synthesized in 1922, it was investigated in humans in the 1940s (around 80 years ago) and formally introduced into clinical practice for the treatment of diabetes in 1957 by Jean Sterne.

  • supports: Metformin: historical overview. (Diabetologia 2017) · cited 1066x in the literature
    "Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes... Metformin was rediscovered in the search for antimalarial agents in the 1940s and, during clinical tests, proved useful to treat influenza when it sometimes lowered blood glucose. This property was pursued by the French physician Jean Sterne, who first reported the use of metformin to treat diabetes in 1957." (abstract, results)
    pubmedfull study (doi)

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.