HRT for Menopause

Symptoms of menopause

*Vasomotor symptoms* Irregular menses Episodic amenorrhea Sleep disturbances Mood swings *Vaginal dryness* Depression

MenoPro Steps

1. Asks Age 2. Asks if patient has Vasomotor Symptoms that impair QOL 3. Asks if patient has tried behavioral/lifestyle modifications for at least 3 months 4. Asks if patient is interested in considering HT and free of contraindications 5. Asks if woman is less than 10 years past onset of menopause 6. Asks if patient has had hysterectomy 7. Asks Patient's race/ethnicity 8. Asks if patient is current smoker 9. Asks if patient has been treated for high blood pressure 10. Asks systolic blood pressure 11. Asks if patient has diabetes 12. Asks if patient has cholesterol lowering medication 13. Asks total cholesterol level 14. Asks patient hdl

Steps for HRT Selection

1. Determine indication/goal of therapy 2. Determine if patient is interested in HRT Therapy 3. Determine if patient has any contraindication to HRT Therapy 4. Determine Appropriate HT type, dose, formulation, route of administration, duration

General Statements in Guidelines

1. Hormone therapy is the most effective treatment for VMS and GSM and has been shown to prevent bone loss and fracture. 2. *Benefits are most likely to outweigh risks for symptomatic women who initiate HT when aged younger than 60 years or who are within 10 years of menopause onset.* 3. Hormone therapy should be individualized 4. The risks of HT in the WHI and other studies differ overall for Estrogen Therapy and Estrogen-Progestogen Therapy, with a *more favorable safety profile for Estrogen Therapy* 5. *Practitioners should use:* 6. Assessment of risk for estrogen-sensitive cancers, bone loss, heart disease, stroke, and VTE is appropriate when counseling menopausal women 7. Decision making about HT should be incorporated into a broader discussion of lifestyle modification to manage symptoms and risks for chronic diseases of aging.

Menopause Treatment Guidelines

2017 Hormone Therapy Position Statement of The North American Menopause Society Considered WHI but also balanced this data with newer information from other randomized controlled trials enrolling younger women

How long should non pharm therapy be used for hot flashes?

3 months

Metabolic syndrome criteria

3 or more of the following: - Abdominal obesity (waist circumference > 35 inches - TG >150 mg/dL - High Density Lipoproten <50 mg/dL - Blood pressure >130/85 mmHG - Fasting Glucose >110 mg/dL

FSH and menopause

An elevated FSH level may indicate a woman is experiencing menopause FSH > 30 mIU/mL

What do the guidelines suggest practitioners should use?

Appropriate HT type, dose, formulation, route of administration Appropriate duration of use to meet treatment objectives Periodic reassessment of changes in a woman's health, and anticipated benefits, risks, and treatment goals over time.

Observational studies in early menopausal women

Benefits outweigh the risks for effects on bone, heart, cognition, GSM, sexual function, and mood

What are the risks of HRT?

CHD Stroke VTE Breast cancer Endometrial cancer Ovarian cancer Lung cancer Gallbladder and Liver

What should you do if compounded bioidentical HT is prescribed?

Concerns about safety should be discussed Indication for prescribing compounded rather than government approved bioidentical HT should be documented (allergy, medical need for lower-than-available dose, different preparation).

Women with early endometrial cancer who have completely successful treatment (including hysterectomy)

Consideration may be given for low-dose vaginal ET for relief of GSM if nonhormone options are not successful, based on limited short-term safety trials.

Duration of HRT Women starting menopause early (before 40)

Continued use at least until the median age of menopause (52) is recommended

Treatment in women who are survivors of breast cancer

Decisions about low-dose vaginal ET should involve the woman's oncologist, particularly for women using AIs who have lowered overall estradiol levels.

Duration of HRT Beer's Criteria

Discontinue systemic HT in women aged 65 years and older is not supported by data

What are relative contraindications of systemic hormone therapy?

Elevated blood pressure Hypertriglyceridemia Impaired liver function and past history of cholestatic jaundice Hypothyroidism Fluid retention Severe hypocalcemia Ovarian cancer Exacerbation of endometriosis Exacerbation of asthma Diabetes mellitus, migraine, systemic lupus erythematosus, epilepsy, porphyria, and hepatic hemangioma

What SSRIs can be used in menopause?

Fluoxetine Citalopram Paroxetine Sertraline

Early Menopause

For women with POI or premature surgical menopause without contraindications, HT is recommended until at least the median age of menopause (52 y) Observational studies suggest that benefits outweigh the risks for effects on bone, heart, cognition, GSM, sexual function, and mood.

Considerations if HRT is for endometrial protection

For women with a uterus if using systemic estrogen: - Endometrial protection requires an adequate dose and duration of a progestogen or use of the combination CEE with bazedoxifene - Progestogen therapy is not recommended with low-dose vaginal Estrogen Therapy, but appropriate evaluation of the endometrium should be performed if vaginal bleeding occurs, given the limits of safety data.

Hypoestrogenism and HRT

For women with hypoestrogenism caused by hypogonadism, POI, or premature surgical menopause without contraindications, HT is recommended until at least the median age of menopause (52 y)

What's the big deal about about HRT?

Go to therapy for years Most effective treatment option for alleviating moderate and severe vasomotor and vaginal symptoms

What are the 2 modes of MenoPro

Health care provider Woman/patient

Purpose of MenoPro

Help clinicians and women/patients work together to personalize treatment decisions based on the patient's personal preferences

Vasomotor symptoms and HRT

Hormone therapy is recommended as first-line therapy for bothersome VMS in women without contraindications

Prevention of bone loss and HRT

Hormone therapy may be considered as a primary therapy for prevention of bone loss and fracture in postmenopausal women at elevated risk of osteoporosis or fractures, primarily for women aged younger than 60 years or who are within 10 years of menopause onset.

What are examples of vasomotor symptoms?

Hot flashes Night sweats

HRT and Ovarian Cancer

If an association between HT and ovarian cancer exists, the absolute risk is likely to be rare and more likely with longer durations Limited observational data have not found an increased risk of ovarian cancer in women with a family history or a BRCA mutation who use EPT.

Duration of HRT Estrogen Progesterone Therapy

Increase duration has potential of increased (rare) risk of breast cancer

Women's Health Initiative (WHI)

Increase the risk in women with underlying CHD risk factors. Increase Risk of breast cancer was also increased after a woman was on combination estrogen and progestogen for approximately 3 years *Should not be initiated or continued for the primary prevention of CHD*

VTE and HRT

Increased risk of VTE w/ oral CEE alone and CEE w/ MPA therapy (highest risk in first 1 - 2 years) For women who initiated HT when aged younger than 60 years, the absolute risk of VTE was rare but significantly increased Higher absolute risks of VTE (with risk of PE) in women initiating HT more than10 years from menopause onset Transdermal HT as well as lower doses of oral or transdermal HT have less effect on risk of VTE There is no evidence of increased risk of VTE with low dose vaginal ET used for genitourinary symptoms

How do the guidelines suggest therapy should be individualized?

Indication(s) or evidence-based treatment goals Woman's age and/or time since menopause in relation to initiation or continuation, Woman's personal health risks and preferences, Balance of potential benefits and risks of HT versus nonhormone therapies or options

Decisions regarding whether to continue systemic HT is women aged older than 60 should be made on ....

Individual basis - QOL - Persistent vasomotor symptoms - Prevention of bone loss and fracture

What does MenoPro provide?

Information needed to determine each step - Lifestyle modifications - Contraindications/ precautions of HT Calculates CVD risk Gives list of products that are optional with doses Helps to determine what is best for patient based on characteristics

WHI: Overall

Landmark trial enrolled few women younger than 60 years and few women who were within 10 years of menopause onset

Breast and endometrial cancer survivors: Treatment of bothersome GSM symptoms

Low-dose vaginal ET used for the GSM has minimal systemic absorption (blood levels in the postmenopause range) and, on the basis of limited observational data, appears to hold minimal to no demonstrated risk for recurrence of endometrial or breast cancer

Lowering doses or hanging to transdermal HT

May be appropriate as women age or in those with metabolic syndromes (hyperTG with a risk of pancreatitis or fatty liver)

What app does Dr Juengel care about?

MenoPro App\\By the North American Menopause Society

Stroke and HRT

No increased risk of stroke in women aged younger than 60 years or who were within 10 years of menopause onset Increased risk of stroke in women who initiate HT when aged older than 60 years and/or who are more than 10 years from menopause onset Lower-dose oral as well as lower-dose transdermal therapy has less effect on risk of stroke, although RCT data are lacking.

Who is a candidate for hormone replacement therapy?

No self history of breast cancer CVD risk < 10% No contraindications

HRT and Breast Cancer

Nonsignificant reduced risk of breast cancer with CEE alone in women with a hysterectomy A rare absolute risk of breast cancer (< 1 additional case/1,000 person-years of use) was seen with daily continuous-combined CEE and MPA in the WHI Duration of HT use may be an important factor in breast cancer risk, because in some studies, risk increased with longer durations of use. Different HT regimens may be associated with increased breast density Breast tenderness, breast density, and breast cancers were not increased with oral CEE plus bazedoxifene compared with placebo. HT use does not further increase risk of breast cancer in women with a family history of breast cancer or in women after oophorectomy for BRCA 1 or 2 gene mutation.

US Preventive Services Task Force

Not all post menopausal women should be prescribed HRT Individualized based on risk factors

Transdermal are better for what women?

Obese Have DM or metabolic syndrom

Safety concerns with bioidentical HT

Possibility of overdosing or underdosing, lack of efficacy and safety studies, and lack of a label providing risks.

Follow Up: WHI

Published data 10 years ago HT has complex pattern of risk and benefits Combination therapy associated with more of increased risks (e.g., myocardial infarction, stroke, deep vein thrombosis, breast cancer, gallbladder disease) (Caused many clinicians and patients to stop using hormone therapy)

CHD Studies with HRT

Reduced risk of CHD in women who initiate HT when aged younger than 60 years and/or who are within 10 years of menopause onset In women who initiate HT more than 10 years from menopause onset, and clearly by 20 years, there is potential for increased risk of CHD The WHI found that both CEE alone and CEE with MPA increased risk of CHD, with potentially greater risk with CEE and MPA, which was significant when initiated in women who were more than 20 years from menopause onset

Duration of HRT Start of HRT

Reduced risk: if started in women aged younger than 60 years or within 10 years of menopause onset Greater risks: if initiated further from menopause onset or in women aged 60 years and older

HRT and Gallbladder and Liver

Risk of gallstones, cholecystitis, and cholecystectomy is increased with oral estrogen-alone and combination HT Observational studies report lower risk with transdermal HT than with oral and with oral estradiol compared with CEE, but neither observation is confirmed in RCTs

What are alternatives to HRT?

SSRIs SNRIs Gabapentin Clonidine Soy Protein OTC

How do you feel about compounded bioidentical HT?

Should be avoided!

Non Pharm Therapy for hot flashes

Smoking cessation Limit alcohol and caffeine Limit hot beverages (e.g., coffee/tea, soups) Limit spicy foods Keep cool, and dress in layers Stress reduction (e.g., meditation, relaxation exercises) Increase exercise Paced respiration

Why do we care about menopause?

The symptoms are bothersome for our patients

HRT and Lung Cancer

There appears to be an overall neutral effect of HT on lung cancer incidence. Smoking cessation should be encouraged, with increased surveillance for older smokers, including current or past users of HT.

Soy protein should not be used in what patients?

Those with a history of estrogen dependent cancers

What are absolute contraindications of systemic hormone therapy?

Undiagnosed abnormal genital bleeding Known, suspected, or history of cancer of the breast Known or suspected estrogen- or progesterone-dependent neoplasia Active deep vein thrombosis, pulmonary embolism, or a history of these conditions Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction) Liver dysfunction or disease

HRT and Endometrial Cancer

Unopposed systemic ET in postmenopausal women with an intact uterus increases the risk of endometrial cancer, which is dose and duration related More risk is seen earlier with higher doses and persisting for several years after discontinuation. *Adequate concomitant progestogen is recommended for women with an intact uterus when using systemic ET.*

Observational evidence in FH of breast cancer

Use of HT does not further alter the risk for breast cancer in women with a family history of breast cancer

HRT FDA Approved Indications

Vasomotor symptoms Prevention of bone loss Hypoestrogenism Genitourinary syndrome of menopause/Vulvovaginal atrophy

What SNRI can be used in menopause?

Venlafaxine

Genitourinary syndrome of menopause/Vulvovaginal atrophy

When isolated genitourinary symptoms caused by menopause are present, low-dose vaginal ET is recommended over systemic ET as first-line medical therapy

Who are considered to not be good candidates for systemic hormone therapy?

Women more than 10 years past menopause

Recommendations for women who are BRCA + w/o breast cancer

Women who are BRCA-positive without breast cancer are at higher genetic risk of breast cancer, primarily ER-negative For those who have undergone surgical menopause (bilateral oophorectomy), benefits of estrogen to decrease health risks caused by premature loss of estrogen need to be considered. On the basis of limited observational studies, consider offering systemic HT until the median age of menopause (52 y). Discussions about longer use should be individualized.

Heart and Estrogen/Progestin Replacement Study (HERS)

Women with established CHD were at an increased risk of experiencing a myocardial infarction within the first year of HT HT should not be recommended for the secondary prevention of CHD