Menopause Care 101

2026 Ogden Surgical-Medical Society CME Conference

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Camille Moreno, DO MSCP

University of Utah Health

Financial Disclosure

This presentation has no ineligible company content, promotes no ineligible company, and is not supported financially by any ineligible company. I receive no financial remuneration from any ineligible company related to this presentation.

Agenda

Terminology

E + P = EPT = Estrogen + Progestogen

E = ET = Estrogen alone

 Stages of Reproductive Aging Workshop (STRAW) +10 Staging System

Menopause Matters

• Median age of natural menopause is 51-52^�
• In US (based on 2020 Census):
• ~63 million women are > 50 or 20% of the US population
• ~6000 enter menopause daily

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• 70-80% of with symptomatic menopause lasting a median of 7-10 years

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Menopause Matters

• Vasomotor symptoms – 70-80%
• Genitourinary syndrome of menopause – 40-60%
• Sleep disturbances
• Depression
• Sexual dysfunction
• Pelvic floor dysfunction
• Cognitive difficulties
• Joints aches/pain

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Menopause Matters

• ↑Cardiovascular and metabolic Risk
• ↑ LDL, ↓ HDL
• ↑ visceral fat
• ↓ lean mass
• ↑ insulin resistance
• ↑ met syndrome
• ↑ atherosclerosis
• ↑MASLD risk
• ↓ Bone mineral density

Reference 7.

Menopause Matters

• Faubion et. al 2023 survey of 4440 women 45-60
• Annual loss of $1.8B
• 11% missed work in year
• 13.% adverse work outcomes
• 6% reduced work hours
• 1% retired/quit/changed jobs

Landmark Trial: Women’s Health Initiative (WHI)

Ref 21.

Ages 50-59: Risks and Benefits of CEE or CEE + MPA per 10,000 Women per Year

Dashed red line:

WHO rare event (≤10/10,000PY)

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Pros and Cons of WHI Pros HT Studies

PROS

• 1^st large scale RCT to assess long-term risk and benefits of HT in postmenopausal women for primary prevention.
• Led to careful consideration of appropriate HT candidate.

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CONS

• Relative risk highlighted over absolute risk with lasting fear of HT
• Lacks external validity for use in young women with symptoms
• avg age 63, 2/3 > 60, 25-50% with prior HT, 60% without VMS, higher E doses
• Assumptions for all HT rather than specific formulation/route
• Inappropriate extrapolation to premature menopause or POI.

Current Guidelines on MHT

For women < 60 years or within 10 years of menopause and have no contraindications,

the benefit-risk ratio is favorable for treatment symptomatic menopause.

MHT = Menopausal Hormone Therapy

Post-WHI Landscape

• Despite updated guidelines, screening, evaluation, and treatment for symptomatic menopause remain low.

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• Most patients feel unprepared for menopause, feel dismissed, and are often not offered clear management options for symptoms.

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• Providers lack training to effectively support patients experiencing menopausal symptoms.
• Duke-Utah provider survey:
• Leading barrier to menopause care: provider education (62%)
• Leading means to improve care: provider education (92%)
• 3 Primary Care and OB/GYN trainee surveys:
• most trainees felt inadequate in menopause management

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Treatments for Symptomatic Menopause

Indications for MHT

• VMS management
• First line therapy for relief of VMS
• Most effective treatment, reduction of symptoms by 75%.
• Prevention of bone loss
• Reduction of bone loss based on RCT
• Reduced fracture risk in postmenopausal women (WHI)
• Genitourinary symptoms
• Restoration of genitourinary anatomy
• Reduction in vaginal pH and symptoms of GSM
• Increase in superficial vaginal cells

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• HRT indicated for premature menopause (age < 40) or early menopause (age < 45).

Contraindications to MHT

• Abnormal genital bleeding
• Breast cancer
• Prior estrogen-sensitive cancers (breast/ovarian/endometrial)
• History of coronary artery disease, stroke, myocardial infarction (MI)
• History of or inherited high risk for VTE
• Severe active liver disease.
• Peanut allergy (Micronized Progesterone)

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Case: VMS

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• Daily estrogen and progestogen
• Higher rates of amenorrhea
• Breakthrough bleeds common at 3-6 months. If bleeding > 6 months, evaluation warranted.

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• Daily estrogen with progestogen added cyclically for 12-14 d each month (or 14d q2-6 months).
• 80% of women will experience bleeding with progestogen withdrawal
• Higher progesterone doses needed for cyclic dosing with potential side effects (ex: mood, bloating).

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MHT ≠ contraception

Does Estrogen Formulation Matter?

17-beta-estradiol (bioidentical)

Compared to CEE

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• ↓Cardiovascular risk

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• ↓VTE risk

Does Route of Estrogen Matter?

Transdermal Estradiol

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Pros

• Avoids first pass effect -- limited effect on clotting factors, lipids, SHBG, TBG, CRP, gallbladder disease.
• No risk of VTE compared to non-users
• Lower CV risk compared to oral

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Cons

• Can be expensive compared to oral
• May have skin irritation
• Risk for transfer within 2 hours

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Does Progestogen Formulation Matter?

Micronized Progesterone (bioidentical)

Compared to MPA

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• Neutral HDL
• ↓ VTE risk
• ↓ breast cancer
• Has a sedative effect
• Most experts prefer micronized progesterone

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How about SERMs?

Bazedoxifene

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• Agonist at bone
• Antagonist at uterus
• Antagonist at breast
• VTE risk

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Ref 44-45

What about Combined Products?

Case: VMS

Case: VMS in a patient with hysterectomy and hypothyroidism

Cardiovascular and Breast Cancer Risk Stratification

HT and Cardiovascular Risk: Timing Hypothesis

HT associated cardiovascular risk is dependent upon timing of HT initiation as it relates to menopause.

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• When initiated early in healthy women < 60 or <10 yrs from menopause, safe/appropriate and potential benefit.

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• When initiated in the setting of advanced atherosclerosis, can have plaque-destabilizing effects.

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ASCVD Risk Consideration

MHT and Breast Cancer Risk

Collaborative Group on Breast Cancer

Meta-analysis of 58 observational studies of > 500K women; nested case-control

All forms, dosages, regimens of E and P combined

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E alone: 0.25 additional cases per 1000 PY

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E + P cyclic: 0.7 additional cases per 1000 PY

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E + P daily: 1 additional case per 1000 PY

RELATIVE Risk increased breast cancer risk form E&P therapy (WHI).

ABSOLUTE attributable risk of MHT

*WHO definition of RARE occurrence 1 cases per 1000 PY

Paradoxical Effect of Estrogen Alone

• Chlebowski et al (Breast Cancer Research and Treatment, April 2024) meta-analysis of 10 randomized trials with a total of 14,282 participants and 591 incident breast cancers.
• RR 0.77 (95% CI 0.65-0.91) indicating a significant reduction in breast cancer incidence.
• CEE and oral estradiol
• “The totality of RCT data supports the conclusion that estrogen alone significantly reduces breast cancer risk”

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Breast Cancer Risk Stratification

When to discontinue MHT?

Systemic Therapy:

• Decision should be individualized on the basis of severity of symptoms and risk-benefit ratio considerations
• Approximately 50% of women will experience recurrence of symptoms with discontinuation

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Topical Therapy:

• Low-dose, local ET may be continued as long as vaginal symptoms are present

Case: VMS & GSM with Breast Cancer History

Non-Hormonal Pharmacological Options for VMS

Physiology of Vasomotor Symptoms

• Disruption of tightly-controlled temperature circuit results in exaggerated heat-loss responses
• Likely involves complex interplay between central nervous system and peripheral physiologic processes
• Thermoregulation affected by loss of estrogen post menopause as well as serotonin, and sympathetic and parasympathetic nerve activity

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How does lack of estrogen cause hot flash?

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The KnDY Neurons

• Thermoregulatory center is altered after menopause by an increase in kisspeptin-neurokinin B-dynorphin (KNDy) neurons
• KNDy neurons inhibited by estrogen
• KNDy Neurons stimulated by neurokinin B
• antagonist of NK receptor would modulate KNDy neuron and reduce VMS

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Neurokinin Inhibitor��Fezolinetant (Veozah®)

• Antagonist that blocks NKB binding on KNDy Neuron
• Oral non-hormonal therapy approved May 2023
• Reduced the frequency of symptoms by more than 50% in most patients
• Improved quality of life scores at 4 and 12 weeks
• Well-tolerated
• Monitor LFT’s
• Magnitude of the effect seems to be on the order of estrogen
• Works in as little as 1-2 weeks

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Non-hormonal Pharmacological Treatment of Vasomotor Symptoms

Case: VMS & GSM with Breast Cancer History

Treatment of Genitourinary Syndrome of Menopause

Genitourinary Syndrome of Menopause (GSM)

Both Vagina and Bladder/Urethra have estrogen receptors

Role of Estrogen

• Vagina 🡪 stimulate cell proliferation and thickening of tissue
• Bladder/Urethra 🡪 E increase blood supply to bladder neck in patients with SUI
• Later menopausal symptom

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Histologic Changes

Symptoms:

• dryness
• Irritation and itching
• dyspareunia
• urinary urgency, dribbling, burning
• yellow vaginal discharge

Differential:

• Vulvar dermatoses (lichen planus, lichen sclerosus)
• Premalignant or malignant vulvar conditions (VIN)
• Infections (Herpes, yeast, UTI)

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Genitourinary Syndrome of Menopause (GSM)

Low-Dose Topical Vaginal Estrogens

• Estradiol tablet (Vagifem; Imvexxy)
• 10 mcg - 3 to 11 pg/mL serum estradiol
• 4mcg even lower
• Twice weekly
• Low dose estradiol ring (Estring)
• 7.5 mcg/day - 5 to 10 pg/mL serum estradiol
• Q 3 months
• Estradiol cream (Estrace)
• results in a serum estradiol level of approximately 40 pg/mL
• ½ applicator (2g) intravag twice weekly
• Conjugated estrogens cream (Premarin)

(no serum ‘test’ for conjugated estrogens)

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Typical estradiol levels in postmenopausal individuals are

< 20 pg/mL

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• Set expectations (3+ months for effect; maintenance)
• Do not need to use a progesterone
• Likely acceptable in breast cancer patients (unless on aromatase inhibitor)

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Alternatives:

• Moisturizers
• Hyaluronic acid
• Intravaginal DHEA (Intrarosa)

Low-Dose Topical Vaginal Estrogens

Case: “I need testosterone”

The Role of Testosterone in Menopausal Hormone Therapy

Evidenced-Based Use

Testosterone therapy for treatment of low sexual desire in postmenopausal women who have been properly screened and diagnosed with hypoactive sexual desire disorder.

Evidence does NOT support its use for

• Treatment or prevention of any age-related condition, including sarcopenia (loss of muscle mass) or osteoporosis
• Treatment of mood changes, decreased energy, or brain fog or for well-being or other symptoms or concerns

Testosterone’s Regulatory “Journey” in Women’s Health

• 2004 - 2 transdermal T products – a patch and a gel underwent FDA approval
• Patch (Intrinsa 300mcg) did show efficacy
• FDA declined to approve based on safety concerns recently brought about by WHI – despite lack of evidence showing an increase in CV events/breast cancer in RCT of testosterone in PMP women
• Intrinsa was approved in Europe (only for oophorectomized women; no longer available)
• 2020 -Testosterone cream 1% (AndroFeme) approved in Australia

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Testosterone Therapy for Desire Disorder�

• Testosterone significantly increases sexual function (satisfactory sexual event frequency, sexual desire, arousal, orgasm, responsiveness) and self-image and reduces sexual concerns and distress in postmenopausal women
• Meta-analyses show no severe AEs with physiological testosterone use
• Long-term safety of testosterone therapy has not been established
• Total serum testosterone concentration should not be used to diagnose
• Off-label testosterone can be considered for select postmenopausal women with desire/arousal disorder

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Testosterone Therapy for Desire Disorder�

• Testosterone formulations targeting the normal premenopause physiologic range recommended (total T 27-57ng/dL)
• No female testosterone product is currently approved by any national regulatory authority; compounded testosterone preparations not generally recommended
• Male formulations can be judiciously used in female doses with serum testosterone concentrations monitored regularly
• a slight increase in androgenic side effects is seen versus placebo

Safety of Transdermal Testosterone

• No clinically relevant changes in
• Lipids
• Liver function
• Hematologic parameters
• Carbohydrate metabolism
• Small weight gain of 1.7kg (p< .05)
• Breast cancer rate consistent with age expected rate (SEER)

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Summary

• Menopausal hormonal therapy safe and effective for symptomatic menopausal transition in women < 10 years from final menstrual period
• Women with a uterus – preferred regimen of EPT is transdermal estrogen and micronized progesterone in standard doses
• Women without uterus - E alone, favorable risk profile compared to EPT
• If GSM alone, use low dose topical estrogen
• Stopping treatment is individualized
• Testosterone can be added for low libido in postmenopausal patients off-label
• New options for vasomotor symptoms are neurokinin Inhibitors

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Questions?

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