Latest / UF Health MedEd Cast / Understanding the Link Between Obesity and Endometrial Cancer

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Understanding the Link Between Obesity and Endometrial Cancer · UF Health MedEd Cast

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  Melanie Cole (Host): Welcome to UF Health Med EdCast with UF Health Shan's Hospital.
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  I'm Melanie Cole, and today we are highlighting obesity
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  associated endometrial cancer.
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  And joining me is Dr.
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  Caitlin Nicholson.
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  She's a clinical assistant professor of gynecologic oncology in the Department
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  of Obstetrics and Gynecology at the University of Florida College of Medicine.
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  Dr.
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  Nicholson, thank you so much for joining us today as we're learning more and more.
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  About obesity-related cancers and diseases.
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  Describe a little bit about the current landscape of endometrial cancers and
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  how the obesity epidemic has shifted that epidemiology of this disease.
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  Do we know about the causal link between obesity and these types of cancers?
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  Dr Kaitlin Nicholson: Absolutely.
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  Thank you so much for having me.
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  I'm, really happy to be here today.
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  so, we know that endometrial cancer is the fourth common cause of cancer in
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  females in the United States, And we know that the incidence of endometrial
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  cancer is increasing, And we think that This is probably related to a variety
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  of factors, but sort of at the forefront is the increasing obesity prevalence.
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  and with this, diabetes and other comorbidities.
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  possibly changes in reproductive behaviors.
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  but it has been shown that patient's with obesity have higher levels of estrogen
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  due to the conversion of the active form of estrogen, estradiol in our fat cells.
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  Melanie Cole (Host): Well, This is such an interesting relationship.
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  We're learning so much more about, and one of the things I think that
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  so many people wonder about is the hormonal and metabolic pathways.
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  As we know Dr.
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  Nicholson, that obesity.
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  Can cause metabolic disorders of many different types.
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  Also, so many shifts in our hormones, so particularly estrogen insulin resistance.
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  We know diabetes type two has been on the rise, inflammation.
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  So tell us a little bit about our latest understanding of how adipose
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  tissue influences that tumor development and progression based on some of the
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  hormonal and metabolic pathways that we're learning more and more about.
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  Dr Kaitlin Nicholson: Sure So, it all is sort of related to excess estrogen.
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  And so we know that, as I said, our, fat cells convert androgens into estradiol.
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  And so patient's with increased fat cells related to obesity will.
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  Therefore have increased levels of circulating estrogen at the same time,
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  patient's with insulin resistance or diabetes, they will have, impaired
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  ability to bind this active estrogen.
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  So it's sort of a twofold, mechanism of increasing circulating estro.
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  And so the way I sort of describe it to patient's is I use a lawnmower
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  and, fertilizer analogy And so, during a normal menstruation and, before
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  menopause, there's sort of this, ebb and flow of estrogen and progesterone
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  that are responsible for ovulation.
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  and, subsequent onset of menses.
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  And so estrogen acts as the fertilizer on the lining of the uterus and
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  progesterone acts like the lawnmower.
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  And so really after menopause, the ovarian production of estrogen and progesterone
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  is almost entirely diminished.
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  And so the lining of the uterus really should be thin without the estrogen
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  or the fertilizer acting on it.
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  And so because we have this peripheral version of the, active form of estrogen
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  in our fat cells, women with excess fat cells have this unopposed estrogen
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  acting on the lining of the uterus without the progesterone to sort of act
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  as the lawnmower to keep an I balance.
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  therefore, patient's can have overgrowth of the lining of the uterus and
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  overgrowth in the form of pre-cancer cells or cancer cells in the endometrium.
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  Melanie Cole (Host): Wow, that's so interesting and I love the
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  way that you described that.
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  And I think in this day, And we think of hormone replacement, we think of all
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  the different ways that women approach.
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  Perimenopause and post menopause.
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  How is the presence of obesity influencing how you clinicians
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  approach that risk stratification and certainly early detection, but also
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  in our comorbid situations that we think about in post-menopausal women.
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  As we lose our estrogen.
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  Tell us how that all ties together and how clinicians are putting
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  that together to work with us.
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  Dr Kaitlin Nicholson: Well, I say, menopause is having a moment and I think
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  there's more and more providers every day, who are certified by the National
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  Menopause Society, to really feel comfortable about talking to patient's
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  about hormone replacement therapy.
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  And so, the big.
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  Take-home is that, patient's with a uterus should not have unopposed estrogen.
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  And so if you are thinking about giving hormone replacement therapy to a patient
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  with a uterus, you really need to give them, some sort of progesterone, whether
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  it's, oral or, in the form of an IUD, to protect them from that excess estrogen.
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  so in terms of risk stratification and early detection of endometrial
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  cancer, really the first clinical indicator, to, alert a provider
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  about, possible endometrial cancer or pre-cancer is postmenopausal
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  bleeding or abnormal uterine bleeding.
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  And a lot of patient's will say, well, there's just a little, pink
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  spot or, it happened once and I really didn't think anything of it.
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  so it's really something that patient's.
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  After menopause should be asked about, at every primary care visit.
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  it's a great way to screen for, endometrial cancer and sort of
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  trigger any, additional imaging or, endometrial sampling.
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  And then for premenopausal women it's a little bit more challenging
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  because a lot of women, especially in that per menopause, phase, can
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  have abnormal uterine bleeding.
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  so, Really having a low threshold to screen patient's with a transvaginal
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  ultrasound and or an endometrial biopsy, especially if these
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  patient's have, increased risks for endometrial cancer, such as obesity.
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  Polycystic ovarian syndrome or anovulation, never being pregnant,
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  having their periods early or going through menopause at a later age
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  or having a strong family history.
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  Those all play into, the risks of endometrial cancer.
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  Melanie Cole (Host): When we think of the treatments, Dr.
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  Nicholson and obesity, I mean, we know that if.
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  Somebody who is living with obesity has any kind of surgical needs, whether it's
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  a knee replacement or a hip replacement.
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  There's always gonna be just a little bit of extra thinking and
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  planning on the surgeon's part.
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  So how does that impact surgical management, both in terms
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  of that technical difficulty and postoperative outcomes?
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  When we think of hysterectomies, when we think of tumor removal, tell us a little
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  bit about what goes into that planning.
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  Dr Kaitlin Nicholson: the standard care of, surgical management.
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  Typically involves a total hysterectomy and removal of the
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  ovaries, fallopian tubes, uterus, cervix, and lymph node sampling.
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  And we try to do this when possible through small incisions, minimally
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  invasive surgery, robotically or traditional laparoscopy.
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  patient's with obesity often, will have.
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  Multiple medical comorbidities, heart disease, kidney disease, liver
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  disease, maybe structural issues like large hernias that may make them
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  less ideal candidates for surgery.
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  And some patient's might not be eligible at all for this sort of standard of
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  care And we may need to pivot to, other.
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  clinically proven, efficacious, but not standard of care.
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  alternatives such as hormonal therapy with, either oral or
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  intrauterine progesterone, or sometimes even primary radiation.
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  but in those patient's that, we are, going to try to get to surgery, we typically
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  have to put them in deep trendelenberg in order to get, all of the bowel out
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  of the pelvic field, in order to be able to operate safely in the pelvis.
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  And, adding that excess adiposity onto the patient's chest can make
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  it really difficult to ventilate.
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  And so, oftentimes they'll have a hard time with anesthesia and, may
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  not being able to complete the case.
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  postoperatively they could have, increased risk of bleeding, infection, delayed
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  wound healing blood clots, especially if they're sedentary, and possibly
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  even cardiovascular complications.
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  Melanie Cole (Host): Wow.
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  So much to think about.
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  Now, when we talk to our patient's weight loss lifestyle interventions
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  are always certainly recommended, but how effective do you see that they
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  might be in reducing that risk or recurrence in endometrial cancers?
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  What do we know about the role of certain.
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  Loss interventions such as bariatric surgery or medical interventions.
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  You know, there's ozempic, there's all these things.
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  Now do, we put that association in a lower risk now?
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  Dr Kaitlin Nicholson: clinically, absolutely, scientifically there's
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  not as much, robust research in this area, but it's, very much
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  a research interest of mine.
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  And so there are some prospective studies looking at this.
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  I think the long of the short of it is that yes.
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  We know that, weight loss can lower the risk of endometrial cancer And
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  the risk of recurrence in those who are already diagnosed with it.
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  But it's unclear how effective weight loss and lifestyle interventions are.
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  And which is more effective than the other.
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  but as I mentioned, There are clinical trials there's one, I believe it's out
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  of, Memorial Sloan Kettering looking at the use of GLP one, receptor agonist.
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  in patient's who are undergoing surveillance for endometrial
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  cancer to see if the usage will decrease the risk of recurrence.
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  And so, more to follow on that.
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  Melanie Cole (Host): Well, This is really such an interesting topic
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  and really an exciting time in your field as we're learning so much more.
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  But one of the more important things is that multidisciplinary
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  approach and collaboration.
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  So how do gynecologic oncologists collaborate with primary care,
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  endocrinology team, nutrition, dietetics?
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  There's so many different.
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  Areas of specialties that could work together for these women.
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  Dr Kaitlin Nicholson: oftentimes, especially, where we practice a
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  lot of patient's coming from rural areas, sometimes a new diagnosis
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  of endometrial cancer or pre-cancer is the reentry point into the
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  medical system for some patient's.
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  And so it's really offers a unique opportunity for GYN oncologists.
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  To partner with primary care or endocrinologists to help patient's address
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  other, potential comorbidities associated with obesity and, really help the
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  patient's, in the full spectrum of their health, to get a handle on everything.
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  so I would encourage folks to, seek out, primary care physicians
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  and, obesity specialists.
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  in the area and, really develop a partnership.
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  I've developed a partnership with one of the obesity specialists here at uf, Dr.
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  Amy Sheer, and, we've really established a multidisciplinary approach to addressing
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  both obesity and endometrial cancer.
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  we're starting a clinical trial That is, looking at GLP one.
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  receptor agonist, in patient's who are not candidates for
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  that, standard of care surgery.
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  And, I think through opportunities like this, you really can,
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  reach a lot of patient's.
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  Melanie Cole (Host): I agree and This is such an interesting conversation and
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  there's so much more we could discuss because it's so far reaching as we
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  look at this obesity epidemic, Dr.
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  Nicholson.
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  But as we wrap up.
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  What areas of research do you feel are most promising for
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  unraveling this connection?
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  How do you envision ai, precision medicine, metabolic
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  targeted therapies reshaping the management in the next decade?
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  and if you want other providers to take-home a key message.
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  About reframing obesity, not just as a risk factor, but as a modifiable,
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  biologically active disease process that could intersect with cancer care.
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  What would you tell them?
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  It's a big ask, but I know you can do it.
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  Dr Kaitlin Nicholson: as clinicians we have this opportunity to, move toward a
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  model that treats obesity with the same seriousness, compassion, and scientific
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  rigor that we apply to every other chronic disease, including cancer care.
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  And I think educating patient's and colleagues about how adiposity
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  drives inflammation, hormonal signaling, immune changes, all of
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  which can accelerate carcinogenesis and affect, disease processes.
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  I think acknowledging that, you know.
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  By improving metabolic health, we can enhance treatment tolerance and possibly
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  reduce risk, of recurrence and, really focus on improvements of quality of life.
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  I think we're lucky at this institution to have a lot of really smart scientists
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  who are interested in, you know, exercise physiology and obesity medicine.
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  And so I've reached out to, several colleagues And we, you trying to look
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  at it from multiple different angles.
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  whether it's, exercise interventions And in patient's who are survivors.
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  or as I mentioned before, the partnership with Dr.
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  Sheer.
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  So, there's really a lot of opportunity, with ai.
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  I think, different, modes like apps and things like that to really be
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  able to help, engage patient's, I think, is gonna be huge for this.
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  Melanie Cole (Host): I agree with you, and thank you so much for such
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  an enlightening discussion, Dr.
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  Nicholson, And for joining us today.
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  And to learn more, you can visit uf health.org/gynecological
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  cancer, or to learn more about this in other healthcare topics at UF
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  Health Shans Hospital, you can always visit innovation dot uf health.org.
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  That concludes today's episode of UF Health Med EdCast with
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  UF Health Chance Hospital.
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  I'm Melanie Cole.