2025_9_17_SHARE_DG.pptx

Gynecologic Cancer and Menopause: Understanding and Managing Health KEY INSIGHTS INTO WOMEN'S HEALTH CHALLENGES AND CARE

Melissa Frey, MD MS

Deanna Gerber, MD

Associate Professor Division of Gynecologic Oncology Department of Obstetrics and Gynecology Director of Genetics and Personalized Cancer Prevention Program

Assistant Professor Division of Gynecologic Oncology Department of Obstetrics and Gynecology

Gynecologic Cancer and Menopause • Overview of gynecologic cancer • Overview of menopause • Menopause management options for gynecologic cancer patients

Gynecologic Cancer and Menopause • Overview of gynecologic cancer • Overview of menopause • Menopause management options for gynecologic cancer patients

Ovarian cancer • Prevalence and Mortality • 21,000 new cases yearly in the US • 13,000 deaths • Risk Factors • Age • Genetic factors • BRCA1/2 pathogenic variants (highest known risk) • Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM) • Moderate-penetrance genes (RAD51C, RAD51D, BRIP1, PALB2) • Family history of ovarian, breast, or colorectal cancer

• Reproductive and hormonal factors • Early menarche / Late menopause / Nulliparity • Endometriosis • Polycystic ovary syndrome (PCOS)

Ovarian cancer • Signs/symptoms • Abdominal or pelvic symptoms • Persistent bloating or increased abdominal size • Pelvic or abdominal pain or discomfort • Early satiety (feeling full quickly when eating)

• Gastrointestinal symptoms • Indigestion, nausea, or upset stomach • Constipation or changes in bowel habits • Loss of appetite

• Urinary symptoms • Urinary urgency (feeling the need to urinate immediately) • Urinary frequency (needing to urinate more often than usual)

• Constitutional symptoms • Fatigue or low energy • Unexplained weight loss

Ovarian cancer • Treatment Approaches • Surgery to remove ovaries, uterus, cervix • Chemotherapy • Targeted therapies for personalized care.

• Challenges and Research • Early detection is difficult • Lack of effective screening

Uterine cancer • Prevalence and Mortality • 66,000 new cases yearly in the US • 12,5000 deaths • Protective Factors • Oral contraceptives (combined estrogen-progestin pills reduce risk) • Progestin-containing IUDs • Multiparity • Regular physical activity

Uterine cancer • Risk Factors • Hormonal and Reproductive Factors • Unopposed estrogen exposure (without progesterone) • Early menarche / Late menopause / Nulliparity • Infertility or anovulatory cycles (often due to conditions like PCOS) • Metabolic and Lifestyle Factors • Obesity • Diabetes • Hypertension • Metabolic syndrome • Physical inactivity • Genetic and Family History • Lynch syndrome • Cowden syndrome (PTEN mutation) • Tamoxifen

Uterine cancer • Signs/symptoms • Abnormal uterine bleeding • Postmenopausal bleeding (most common presentation) • Heavy, prolonged, or irregular menstrual bleeding in premenopausal women • Other Symptoms • Pelvic pain or pressure • Pain during intercourse (dyspareunia) • Difficulty or pain with urination • Enlarged uterus or abdominal mass (less common, often later stage)

Uterine cancer • Treatment Approaches • Surgery to remove ovaries, uterus, cervix • Radiation • Chemotherapy • Targeted therapies for personalized care.

Cervical cancer • Prevalence and Mortality • 13,000 new cases yearly in the US • 4,000 deaths

Cervical cancer • Risk factors • Sexual and Reproductive Factors • Early onset of sexual activity • Multiple sexual partners • History of sexually transmitted infections (e.g., chlamydia, HIV) • Immunologic and Medical Conditions • Immunosuppression (HIV infection, organ transplant recipients, chronic immunosuppressive therapy) • Lifestyle and Environmental Factors • Smoking (increases risk of squamous cell carcinoma of the cervix) • Reduced access to screening and vaccination

Cervical cancer • Treatment Approaches • Surgery (excision of part o cervix for early disease vs. removal ovaries, uterus, cervix) • Radiation • Chemotherapy • Targeted therapies for personalized care • HPV vaccination for prevention

Side effects from gynecologic cancer treatment Common physical side effects Fatigue, pain, and sexual dysfunction are frequent physical side effects impacting daily life after treatment

Emotional and psychological impact Emotional distress such as anxiety and depression commonly affect women, requiring professional support

Fertility concerns Infertility is a significant concern for younger women undergoing gynecologic cancer treatment

Gynecologic Cancer and Menopause • Overview of gynecologic cancer • Overview of menopause • Menopause management options for gynecologic cancer patients

Surgical menopause

Gynecologic cancer

Removal of uterus, ovaries, fallopian tubes

Chemotherap y

Menopause

Symptoms of menopause • Vasomotor symptoms • Hot flashes (sudden feeling of heat in face, neck, chest) • Night sweats (hot flashes during sleep, often causing awakening) • Genitourinary symptoms • Vaginal dryness • Pain with intercourse (dyspareunia) • Recurrent urinary tract infections • Urinary urgency or incontinence • Sleep and cognitive symptoms • Insomnia • Difficulty falling or staying asleep • Memory lapses or difficulty concentrating (“brain fog”)

Symptoms of menopause • Mood and emotional symptoms • Mood swings • Irritability • Anxiety or depression • Physical changes • Weight gain, especially central (abdominal) • Joint or muscle aches • Skin and hair changes (dryness, thinning)

Long-term health consequences

Bone health

Cardiac health

Neurologic health

Gynecologic Cancer and Menopause • Overview of gynecologic cancer • Overview of menopause • Menopause management options for gynecologic cancer patients

Quality of life considerations • Physical symptoms: Hot flashes, vaginal dryness, insomnia, fatigue • Psychological impact: Anxiety, depression, body image concerns • Sexual health: Decreased libido, dyspareunia, relationship strain • Social functioning: Return to work, family roles, social engagement

Survivorship plans and multidisciplinary Care Holistic survivorship care Menopause management is integrated into care plans to provide coordinated support for gynecologic cancer survivors Multidisciplinary team approach Involving oncologists, gynecologists, primary care, and mental health experts improves care quality and continuity Communication and decision-making Regular meetings and shared electronic health records facilitate effective communication and patient-centered decisions Patient empowerment Survivorship plans provide clear guidance and resources, empowering women on their healthcare journey

Lifestyle interventions Physical activity benefits Regular exercise reduces hot flashes, improves mood, and enhances sleep quality during menopause Healthy diet importance A balanced diet rich in fruits, vegetables, and whole grains supports overall health and eases menopausal symptoms Mind-Body therapies Yoga, meditation, acupuncture, and tai chi promote relaxation and reduce stress during menopause

Complementary & integrative therapies Acupuncture benefits Acupuncture can reduce hot flashes and improve sleep quality during menopause, providing relief from vasomotor symptoms Herbal supplements use Herbal supplements like black cohosh and soy isoflavones are used for menopausal symptom relief but require cautious use Psychological interventions Cognitive behavioral therapy helps manage mood disturbances, anxiety, and insomnia by changing negative thought patterns

Patient preferences and counseling OPTION

PREFERENCE (%)

Lifestyle

30

Pharmacologic

40

Mind-Body

20

Complementary

10

To use hormones or not?

Non hormonal options2 • SSRI/SNRI • Paroxetine • Venlafaxine • Citalopram/escitalopram

• Gabapentin • Oxybutinin • Clonidine • NK3 Receptor antagonists

Systemic Options • Transdermal (non oral) estradiol • Oral estradiol • Oral conjugated equine estrogens • Progestin • Oral micronized progesterone • LNG IUD • Medroxyprogesterone acetate

• No progestin needed • Conjugated equine estrogen + bazedoxifene

1

Preferred; 2 Practice Bulletin #141: Management of Menopausal Symptoms. Obstet Gynecol 2016; 127: 166; 3 FDA approved

Hormone replacement therapy and cancer

Hormone replacement therapy after cancer

Managing menopause after cancer. The Lancet

Endometrial cancer Hormone-Dependent Cancer Endometrial cancer is largely dependent on estrogen and progesterone, influencing treatment approaches and contraindications historically.

Surgical Treatment and Menopause Early-stage endometrial cancer is commonly treated surgically, often causing premature menopause

Evolving HRT Safety Emerging evidence suggests HRT can be safe for select early-stage patients, improving symptom management and quality of life.

Is HRT use safe in endometrial cancer?

Clinical study findings Studies show HRT does not raise recurrence rates in stage I endometrial cancer survivors

Patient selection criteria HRT benefits those with low-risk histologies and no residual disease after surgery

Individualized decision-making Treatment decisions consider patient preferences, symptom severity, and oncologic risk

Hormone use in ovarian cancer Hormonal profile of ovarian cancer Ovarian cancer is generally not driven by hormones, allowing safer consideration of estrogen replacement therapy Impact of oophorectomy Removal of ovaries causes abrupt menopause and significant symptoms in ovarian cancer survivors Role of hormone replacement therapy HRT improves quality of life by relieving vasomotor symptoms and preventing osteoporosis in survivors

Clinical evidence and recommendations Study findings on HRT No significant difference in survival or recurrence rates found in ovarian cancer survivors using HRT versus those not using it

Symptom improvement HRT improves vasomotor symptoms, bone density, and overall quality of life in disease-free ovarian cancer survivors

Clinical guidelines Current guidelines recommend considering HRT for ovarian cancer survivors when non-hormonal treatments are insufficient

Balancing safety and relief Effective symptom control with HRT must balance quality of life and oncologic safety

Cervical cancer and hormones Hormonal neutrality of cervical cancer Cervical cancer is not generally not estrogen-dependent, allowing safe use of HRT for survivors

Treatment effects on menopause Surgery and radiation often cause premature menopause with symptoms needing management through therapy

Informed treatment decisions Understanding hormonal profile guides safer, effective treatments enhancing survivorship quality of life

What are the indications for hormone therapy?

• • • • • • •

Hot flashes Night sweats Genitourinary syndrome of menopause (GSM) Poor sleep Adverse mood Prevention of postmenopausal bone loss Premature hypogonadism

NIH Consens State Sci Statements. 2005 July 2022.

HRT modalities and risk stratification HRT administration methods HRT can be given systemically or locally, with transdermal patches preferred for lower thrombotic risk and vaginal estrogen for GSM treatment

Risk stratification importance Risk stratification guides HRT eligibility, ensuring low-risk endometrial cancer survivors can use HRT safely while high-risk patients avoid it

Guideline-based individualized care Clinical guidelines recommend personalized treatment based on cancer type, age, symptoms with shared decision-making

Pharmacologic therapies THERAPY

SYMPTOM REDUCTION (%)

SSRIs

45

SNRIs

40

Gabapentin

35

Clonidine

25

Nonhormonal pharmacologic options • Gabapentin: effective for hot flashes at night • Clonidine: used for hot flashes • Ospemifene: SERM for dyspareunia, acts on estrogen receptors • SSRIs/SNRIs: • Modulate serotonin/norepinephrine to reduce vasomotor symptoms • Also useful with mood swings • Paroxetine: Only FDA-approved nonhormonal treatment for hot flashes

Fezolinetant (Veozah) • Mechanism of Action: Neurokinin 3 receptor antagonist that modulates thermoregulatory center in hypothalamus • Indications: Moderate to severe vasomotor symptoms associated with menopause • Side Effects: Elevated liver enzymes, abdominal pain, diarrhea, insomnia • Clinical Considerations: • Monitor liver function before and during treatment • Nonhormonal option for patients with contraindications to estrogen • Approved by FDA in 2023 as first-in-class therapy

Hormone replacement therapy after cancer

Managing menopause after cancer. The Lancet 2024.

Comprehensive approaches to vaginal symptoms Lifestyle Modifications Lifestyle changes such as regular sexual activity and pelvic floor exercises help maintain vaginal health and elasticity Non-Hormonal Treatments Use of vaginal moisturizers and lubricants with hyaluronic acid provides hydration and tissue repair without hormones.

Hormonal Therapies Local estrogen therapies offer targeted symptom relief with minimal systemic effects, essential for moderate to severe cases Emerging Interventions CO2 laser treatments and SERMs provide innovative options, stimulating tissue repair with fewer risks than traditional hormones.

Bone and cardiovascular health Menopause and bone health Estrogen deficiency during menopause decreases bone density, increasing fracture risk in survivors Managing bone health Bone health is managed with calcium, vitamin D, weight-bearing exercise, and bisphosphonate medication Cardiovascular risks post-menopause Menopause alters lipid profiles and vascular function, increasing cardiovascular disease risk Lifestyle and prevention Lifestyle changes including diet and physical activity are vital to prevent bone and heart diseases

Psychosocial and sexual health support Emotional impact and challenges Cancer diagnosis and menopausal symptoms cause anxiety, depression, and changes in self-esteem in survivors Changes in body image and sexual function Survivors face altered body image and sexual health issues, affecting intimate relationships

Access to support services Counseling, support groups, and sexual health specialists provide essential care for survivors

Tailored interventions and communication Cognitive-behavioral therapy and sexual rehabilitation improve resilience and quality of life

Take home points Personalized treatment approach Customized treatment and shared decision-making are essential for managing menopausal symptoms safely

Quality of life considerations We need to consider sexual health, mood, and sleep quality

Clinical consensus Gynecologic oncologists widely support HRT for managing menopausal symptoms in this population

Thank you!

Questions?