Highlights from the Menopause Society 2023 Annual Meeting

Forging new frontiers with "Precision Medicine"

Last week the Menopause Society - formerly known as the North American Menopause Society (NAMS) - wrapped up the 2023 Annual Meeting in Philadelphia, PA. This meeting was full of some great science and clinical pearls, hanging with my friend and Feisty colleague, Selene Yeager (check out her awesome blog post 8 Hot Takes from the Menopause Society 2023 Annual Meeting), and reconnecting with the city where my career began.

There was a lot of heavy science at this meeting, so my goal today is to try to make sense of it all and translate it into actionable measures for me, as a clinician, and for the women I care for.

Opening Symposium - Precision Oncology for Midlife Women

Precision Medicine is the most recent evolution in clinical practice. With the advances in genome analysis technology, clinicians have tools that can analyze genetic sequences and methylation patterns that regulate these sequences and provide a profile of an individual’s disease risk and metabolic patterns. These findings guide specific recommendations for prevention, training, and nutrition unique to that individual. My colleagues at Wild Health have been doing this for years and excel at it!

But Precision Medicine goes beyond genetic analysis. It refers to utilizing all the clinical tools available to assess a patient’s risk and craft holistic treatment plans specific to their circumstances and their goals. Here are some of the discussion points raised during this symposium:

• Cancer prevention: Use of gene analysis technology and hereditary cancer gene screening panels to identify those at high risk.

• Risk stratification: Traditionally, screening has been less effective for low-risk individuals with a higher incidence of false positive results leading to additional procedures, risk, and patient anxiety. Advances in knowledge about cancer risk factors and gene analysis technology that can identify those with hereditary risk factors can better identify higher-risk populations and thus make screening more effective for these individuals.

• Early diagnosis: Use of cell-free DNA found in the bloodstream, tumor biomarkers, advanced “radiomics” such as PET/MRI scanning, high-resolution mammography, and analysis of the data using artificial intelligence (AI) to help to fully characterize cancer and identify them early.

• Individualized treatment: Using these tools to characterize a cancer with greater detail and precision can help oncologists tailor treatments that are most effective for that specific type of tumor.

• Detection of residual disease post-treatment: Cell-free DNA and gene analysis technology allow for the detection of tumor DNA and circulating tumor cells (CTCs) in the blood stream. The presence of these cells and tumor DNA in the bloodstream are associated with disease recurrence and allows targeted therapy to be initiated before the disease recurs or metastasis (spread) to other organs.

These general concepts were reviewed for breast, ovarian, cervical, and colon cancer. Each has its own limitations and effectiveness of screening.

• Ovarian cancer: No effective screening test. Depends more on identifying patients at high risk and strategic surveillance or in some cases, prophylactic surgery.

• Cervical cancer: Pap smear cytology and HPV continue to be the mainstay of screening and are effective. Decisions for treatment depend on risk stratification: HPV subtypes, length of time with abnormal screening tests, smoking status, etc.

• Breast cancer: Traditional mammography has limitations in low-risk populations with variability relative to the radiologist reading the images, increased false positive rate resulting in additional procedures and patient anxiety. False negative results also occur particularly in women with increased breast density. As a result, researchers are focusing on risk stratification using traditional models, such as the Gail Model, as well as higher-resolution breast imaging and image analysis using AI to reduce the false positive and false negative rates of mammographic screening.

• Colon cancer: Again, risk stratification is a primary focus. For low to average-risk individuals, there is a trend toward using less invasive screening modalities such as Cologuard, fecal occult blood gFOBT or immunochemical tests (FIT) first, then proceeding to colonoscopy in the event of a positive test.

New Kid on the Block - Estetrol (E4) for Contraception and Relief of Menopausal Symptoms

Estetrol is a type of estrogen that is naturally occurring and exclusively produced by the human fetal liver and is only seen during pregnancy in adult life.

E4 is a NEST: Natural/Native Estrogen with Selective Action on Tissues, meaning that the action of the estrogen is different from one tissue to the next. E4 has a favorable effect on the vagina, endometrium, bone, and cardiovascular system. It has a neutral effect on the liver with little impact on triglycerides, blood clotting factors, and sex hormone binding globulin, unlike estradiol (E2)derivatives. E4 has anti-estrogenic effects on breast tissue inhibiting the stimulatory effects on breast tissue proliferation seen with E2 derivatives.

In 2021, the FDA approved Nextstellis, an effective, oral contraceptive pill that contains 3mg of drosperinone (synthetic progestin) and 14.2mg of Estetrol (E4) for 24 days of active pills and 4 days of inactive pills. This presents a favorable alternative to traditional estrogen/progestin oral contraceptive pills for those women who may have specific risk factors.

Studies are underway evaluating the safety and efficacy of E4 for the treatment of menopausal symptoms such as hot flashes and vaginal dryness in menopausal women. So far, results have been favorable, however, there is not yet an FDA-approved formulation for menopausal HT.

Both Estetrol (E4) and estradiol (E2) derived contraceptive pills carry a similar risk for venous thromboembolism (VTE) or deep venous blood clots at 3.6 events per 10,000 women-years.

Hormone Therapy on the Molecular Level - Selective Targeting of Estrogen Action on Cells and Tissues

The general theme of “precision” therapy continued with this lecture series on selective estrogen receptor modulators (SERMs) and tissue-selective estrogen complexes (TSECs)

What is a SERM? A SERM is a compound that has differing effects on estrogen receptors of different tissues. For example, Tamoxifen, a common medication used for breast cancer treatment stimulates estrogen receptors in the uterus but has the opposite effect on estrogen receptors in the breast.

• The development of SERMs with different tissue and receptor characteristics is at the forefront of breast cancer research. Another type of compound, SERD’s (selective estrogen receptor “degraders") are also showing promise for targeted breast cancer treatment.

What is a TSEC? A TSEC is a combination of a SERM and an estrogen that creates a tissue-selective molecular complex that affords protection of a given tissue by the SERM but also provides the power of symptom relief afforded by the estrogen.

• Duavee (conjugated estrogen 0.45mg / bazedoxifene 20mg) is an FDA-approved medication for the treatment of menopausal hot flashes. Unlike traditional hormone therapy, a progesterone is NOT needed in combination with estrogen in women who have a uterus. The SERM (bazedoxifene) affords protection to the endometrial lining while the estrogen provides relief for menopausal symptoms.

• Bazedoxifene alone and in combination with estrogens have also been studied with favorable effects on breast and vaginal tissue, bone, and lipid parameters in a series of well-done randomized trials. (Selective Estrogens, Menopause and Response to Therapy (SMART) Trials).

• Bazedoxifene and conjugated estrogens may also be effective in the treatment of endometriosis, a common disorder that causes pelvic pain and is associated with infertility. More study is needed in this area.

Bone Health

Again, precision therapy is the theme. Osteoporosis and associated fracture is a leading cause of morbidity and mortality in aged women. More attention is being paid to identifying risk factors and early detection of bone loss so that interventions can occur earlier before bone loss becomes severe and fracture risk is high.

• FRAX tool - considers lifestyle factors, medical history, and other parameters in addition to bone mineral density (BMD) assessed by DEXA scan to assess risk.

  • A score of >/= 20% risk of major osteoporotic fracture or >/= 3% risk of hip fracture is diagnostic of osteoporosis even in the absence of a DEXA scan T score of -2.5

• Vertebral (spine) imaging to assess a “trabecular bone score (TBS)” as a measure of bone microstructure which can be coupled with the DEXA scan to provide an “adjusted” T-score.

• High-resolution peripheral quantitative CT scan (HRpQCT): Another measure of bone architecture that is more predictive of fracture than DEXA, but is not FDA-approved or widely available.

Treatment of osteroporosis - The “Step therapy” (fail first) method involves starting with the least expensive, widely available anti-resorptive medications and considering anabolic treatments only after the anti-resorptive medications have failed is a one-size-fits-all approach that managed care companies love. But in reality, this is not supported by the current research.

• Care should be individualized and the woman’s life stage considered when prescribing treatment. For example, younger women whose bone turnover rates are still high (due to cycling estrogen) can benefit more from anti-resorptive medications (bisphosphonates like Fosamax) whereas older, menopausal women whose bone turnover is lower can benefit more from anabolic therapy (such as Forteo or Prolia).

Miscellaneous “Pearls”

Premature Menopause - Although there is no FDA-approved testosterone product for women, the expert consensus is that testosterone can be considered for women with premature menopause who suffer from hypoactive sexual desire disorder (HSDD) or “low-libido”.

The “Statins” story - Treatment of high cholesterol with statins may be beneficial for intermediate to high risk for experiencing a cardiovascuar event such as heart attack or stroke in the next 10 years. A helpful risk assessment tool is the 10 year ASCVD risk calculator : <5% is considered low risk, 5-20% is considered intermediate risk and >20% is high risk.

Review of the 2023 Non-Hormone Therapy Position Statement - This statement received a lot of attention when it was released earlier this year following the FDA-approval of Fezolinetant, a non-hormonal, first in class treatment for hot flashes. You can find a review of this position statement in the Athletic Aging Archived Medical Updates. There are two FDA-approved, prescription non-hormonal options that are effective for freducing hot flashes:

• Paroxetine salt 7.5mg once daily

• Fezolinetant 45mg once daily

Disinformation and Misinformation in menopause - We have all seen some crazy stuff circulating on social media, TV news, and other outlets and it’s sometimes enough to make one’s head explode. I applaud the Menopause Society for approaching this head-on, however, everyone who publishes on this topic - including the Menopause Society - should be held to account through the exchange of respectful and constructive dialog.

• Bring back the microphones. Participants can no longer directly ask a speaker questions following a presentation. All questions were entered via an app and then filtered and pre-selected by the session moderator. There were topics raised by various presenters that were overlooked by the moderator and deserved a respectful exchange between participant and speaker.

• Get the word out. The Societies, to their credit, realize the need to utilize social media and other resources to better to reach women and connect with them so that they can deliver their message with credibility.