The Latest in Menopause: Part 1

By: Rachel Novik, DO • Madeline Cohn, DO • Posted on October 11, 2023

Highlights From The Menopause Society Annual Meeting: Part 1

New Medications

1. Estetrol for Contraception and Menopause

There are four different types of naturally occurring human estrogens:

Estrone (E1)
Estradiol (E2)
Estriol (E3)
Estetrol (E4)

While much is known about E1, E2, and E3, with E2 being the most potent, more research is focusing on the role that E4 can play in both contraception and menopause symptom management.

E4 is produced in the fetal liver, only found in the adult body during pregnancy at which point levels can be detected in the maternal urine as early as nine weeks. Unlike E1, E2 and E3, E4 does not convert to any other form of estrogen. Unlike other forms of estrogen, E4 is deemed a Natural Estrogen with Selective action on Tissues (NEST) with higher activity on estrogen receptor alpha (ERa) than estrogen receptor beta (ERb). This means it has agonist or positive effects on the ERa in the vulva, endometrium, bone and cardiovascular system with weak or minimal effect on the ERa in the breast and liver.

When combined with drospirenone, E4 has been shown to be an effective form of contraception with <1% chance of pregnancy and good cycle control without evidence of decreased effectiveness in obese patients. It has also shown to have a low side effect profile with a very low rate of blood clot and limited effects on lipid and carbohydrate metabolism.
In menopause, E4 has been shown to reduce frequency and severity of vasomotor symptoms, improve the health of vaginal tissues without impact on coagulation markers and possible benefits on good cholesterol and blood sugar levels.

Nextsellis® with estetrol and drospirenone is available for hormonal contraception. We are still waiting for oral estetrol to be approved for hormone therapy use.

2. Bazedoxifene + CE, Tissue Selective Estrogen Complexes (TSECs)

A medication class called tissue selective estrogen complex (TSEC) is a combination medication that combines a selective estrogen receptor modulator, or SERM, and conjugated estrogen to provide relief of menopausal vasomotor symptoms, provide bone protection, and allow for additional endometrial safety without the use of a progestin.

Bazedoxifene is a SERM medication used to treat osteoporosis. Studies assessing the efficacy and benefit of bazedoxifene showed improvement in lumbar bone mineral density at both 20 and 40 mg doses.

The SMART trial evaluated the safety and efficacy of a TSEC by pairing bazedoxifene with conjugated estrogen. The study found the following:

A significant reduction in the frequency and severity of vasomotor symptoms.
Increased bone mineral density and decreased bone turnover compared to placebo.
Lower rates of endometrial, hyperplasia and higher rates of amenorrhea.
Patients also reported improved vaginal dryness and less painful intercourse.

Note: Duavee® a TSEC combining conjugated estrogen and bazedoxifene is back on the market.

3. NK3 Receptor Antagonists (Fezolinetant) for Treatment of VMS

The new, non-hormonal drug to treat hot flashes and night sweats, Veozah®, is one many physicians are excited about. Veozah®, or fezolinetant is an NK3 receptor agonist that blocks NKB, which triggers vasomotor symptoms such as hot flashes.

Studies found that patients taking the medication had a significant decrease in frequency and severity of vasomotor symptoms as early as week four and additionally at week 12.

Common side effects include:

Abdominal pain
Diarrhea
Insomnia
Back pain
Hot flashes

Patients with significant kidney or liver disease and patients taking other CYP inhibitor medications should avoid Veozah®. Physicians should monitor baseline, liver enzymes at three, six, and nine month intervals. Those who are eligible, and with commercial insurance, can visit veozah.com for a savings card.

The FDA also added new recommendations for patients and health care professionals about increasing the frequency of liver function testing, adding monthly testing for the next 2 months after starting Veozah and then at months 3, 6, and 9 of treatment as already recommended. The updated prescribing information also instructs patients to stop the medicine immediately and contact the health care professional who prescribed the medicine if signs and symptoms of liver injury occur.

Cancer Screening

Cell-Free DNA for Cancer Screening

Cell free DNA is a blood test that looks for genetic variations associated with different diseases.

It can test for circulating tumor DNA and has the potential to be used for cancer screening.
It is minimally invasive and low cost.
It may eventually allow for the detection of cancer, treatment, selection, monitoring of disease, burden, patient, prognosis, and disease surveillance. However, more data is needed at this time.

Cancer Screening Guidelines: Cervical, Ovarian and Colon

Cervical

Cervical cancer screening guidelines have changed significantly over the past several years.

As per current 2020 ACS guidelines, cervical cancer screening should begin at age 25 and be continued until age 65, at which point patients can discuss with their clinician when to discontinue screening based on their prior results.
The preferred screening method based on these new guidelines is primary HPV testing every 5 years.
Management of abnormal results should be based on the patient's risk factors and prior screening results.

Colon

Colon cancer screening saves lives, but more and more people are being diagnosed with colon cancer younger than in the past.

As per the most recent 2021 USPSTF guidelines, colon cancer screening should begin at age 45 until the age of 75, at which point it is recommended to discuss with your clinician when to discontinue screening.
The two most common categories of screening are the stool based tests and colonoscopy.
Discuss with your clinician which of these tests is the best option for you.

Ovarian

Ovarian cancer is the 2nd most common gynecologic cancer behind uterine/endometrial cancer, but is the #1 cause of mortality among gynecologic cancers. Unfortunately, there is no screening for ovarian cancer, and this lack of early screening and detection methods make it difficult to diagnose ovarian cancer in early stages. Early ovarian cancer is not a silent disease. It usually presents with symptoms such as abdominal pain, abdominal fullness, increased abdominal girth, bloating, and sometimes vaginal bleeding, urinary or GI symptoms.

While there are many exciting novel approaches to screening and early detection on the horizon, nothing yet has been shown to be truly effective.

Use of combined oral contraceptive pills as well as bilateral salpingectomy, or tubal removal for the purposes of sterilization, have been shown to be effective at reducing the risk for ovarian cancer.
This is especially true for patients at high risk, such as BRCA1 and BRCA2 mutation carriers.
While not all patients are candidates for oral contraceptives or bilateral salpingectomy, these methods can be considered for women who want to reduce their risk.

Osteoporosis and Bone Quality

Osteoporosis is a lifelong disease that warrants lifelong attention and treatment decisions should be individualized with consideration of all available clinical information, including bone mineral density, age, fracture risk, and patient preference. Fracture risk stratification can guide selection of initial therapy. The FRAX score uses epidemiologic risk factors that are independently associated with poor bone quality and fractures. For example, it can help clinicians identify women with osteopenia who are at high risk of fracture and should be started on treatment to prevent bone loss and fractures.

Osteoporosis Medications

Consider medication to prevent rapid bone loss in women who are perimenopausal or menopausal. The menopause society recommends:

Hormone therapy, or Duavee®, for younger healthy menopausal women
Bisphosphonates if estrogen is contraindicated, or not tolerated
Raloxifene if breast cancer risk is a concern

Osteoporosis Screenings

DXA

Dual Energy Xray Absorptiometry (DXA) is the gold standard for assessing bone mass and fracture risk. But there are some newer technologies clinically available, which may improve risk stratification.

VFA

Vertebral Fracture Assessment (VFA) assesses vertebral fractures using DXA densitometry. Analyzing vertebral fractures in conjunction with bone mineral density may lead to diagnostic information on fracture risk and augment treatment.

TBS

Trabecular bone scoring (TBS) measures bone quality. It uses DXA spine images to assess microarchitecture and independently predicts fracture risk.

IMI

Impact microindentation (IMI) is a direct measure of bone material properties. A fine probe driven into the surface of the tibia. The bone material strength index (BMSI) is the distance probe extends. The lower the BMSI, the greater the risk of fracture.

FEA

Finite Element Analysis (FEA) uses HRpQCT (High Resolution peripheral Quantitative Computed Tomography) to create a 3-D stack of high-resolution slices. This allows for non–invasive evaluation of bone stiffness and strength at the tibia and radius. The Integrates all HRpQCT parameters into a single measurement. The FEA most predictive imaging option, more so than DXA, but it is neither FDA approved, nor widely available.

Markers of bone turnover such as collagen breakdown products and other molecules released from osteoclasts/blasts during the process of bone resorption and formation measured in the blood and urine. This testing can provide insight into remodeling, it is noninvasive, and can be correlated with fracture risk. However, it is not diagnostic and has been shown to have significant variability with results.

Stay tuned for Part 2 of this column series, where we will share updates on cardiovascular health, cognitive health, sexual health, menopause treatments, and combating medical misinformation in menopause.

Be Strong, Be Healthy, Be in Charge!

Rachel Novik, DO and Madeline Cohn, DO

About Rachel Novik, DO

Rachel Novik, DO is a Board Certified Family Medicine physician. She is a first year clinical Specialized Women’s Health Fellow at the Cleveland Clinic Center for Specialized Women’s Health.

Dr. Novik graduated from New York University with a Bachelor’s Degree in Social Work and a minor in Child and Adolescent Mental Health. She then completed a post-baccalaureate degree for pre-medical sciences at John Carroll University and ultimately attended Ohio University’s Heritage College of Osteopathic Medicine, at their Cleveland campus.

Dr. Novik graduated from University Hospitals St. John Medical Center’s Family Medicine Residency program, where she served as chief resident and helped create a women’s health curriculum. She has a passion for working with women at all stages of their lives. During residency, she developed a desire to focus her practice on women in their middle and later decades, where care gaps often exist.

About Madeline Cohn, DO

Madeline Cohn, DO is a Board Certified Family Medicine physician. She is a first year clinical Specialized Women's Health fellow at the Cleveland Clinic Center for Specialized Women's Health.

Dr. Cohn graduated with her Bachelor's degree in Psychology and Cellular and Molecular Biology from Austin College in Sherman, Texas. She attended medical school at the University of North Texas Health Science Center Texas College of Osteopathic Medicine in Fort Worth, Texas. Dr. Cohn completed her residency at Case Western Reserve University MetroHealth in Cleveland, Ohio, where she served as chief resident.

Dr. Cohn is passionate about becoming an educator and leader within the field of women's health, and she hopes to empower her patients to become advocates for their own health.

women's health, the menopause society, estetrol, contraception, menopause, hormones, estrogen, osteoporosis, Bazedoxifene, bone, cancer screening, cancer, cervical cancer, colon cancer, ovarian cancer, hormone therapy

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