UPDATE ON HORMONE REPLACEMENT THERAPY LEIGH S. WALSH, M.D.

• I have no disclosures

- Guidelines for Prescribing Hormone Replacement Therapy Including Bioidentical Hormones - Treatment Options for Menopausal Symptoms

- Risks and Benefits of Hormone Replacement Therapy

CURRENT GUIDELINES FOR PRESCRIBING HRT Background: - WHI published in 2002 - prior to this HRT thought to prevent CHD in women - 2 arms in the study Estrogen + placebo Estrogen/Progesterone + placebo - 160,000 women enrolled between the ages of 50-79 - average age 63 - One hypothesis was that HRT would result in decrease CHD

Background cont. - Study in fact found that women on HRT were 29% more likely to have CHD However - Out of 160,000 women entered, only 3.5% were between the ages of 50-54 - Perimenopausal or symptomatic menopausal women were excluded - A big criticism of WHI has been the high average age and lack of symptomatic women entered - When the data were re-examined and stratified by age there was no significant increased risk of CHD in HRT users aged 50-59. - In HRT users aged 50-59 mortality decreased by 30% compared to placebo

CURRENT RECOMMENDATIONS FOR PRESCRIBING HRT IT IS USUALLY SAFE IN YOUNGER MENOPAUSAL WOMEN.

What are the current recommendations?  There is insufficient evidence to recommend HRT for the prevention of chronic disease  Women who are at low risk, recently menopausal or less than 60 can safely use HRT  Start with the lowest effective dose for the shortest needed time  Long term therapy is not contraindicated in low risk patients who are symptomatic

Current Recommendations Cont.  Vaginal estrogen is a good option for women whose primary symptoms are genitourinary ( minimally absorbed into the bloodstream)

 Women with an intact uterus should not be given unopposed systemic estrogen because it increases the risk of endometrial cancer  In women with a history of low risk endometrial or breast cancer vaginal estrogen may be an option in consultation with the patient’s oncologist.  Transdermal estrogen does not increase the risk of VTE due to first pass effect

Bioidentical Hormones  Many women are turning to hormones that are compounded, either because they are not getting relief from standard FDA approved HRT, or because they perceive them as being more natural to what is produced by the human body  There are FDA approved bioidentical hormones including estradiol and micronized progesterone  There are safety concerns with compounded HRT.  Some preparations not regulated by the FDA  Unregulated preparations have no requirement for package labeling or warnings for potential risks  Wide variations in bioavailability, making under and over dosage possible

Bioidentical Hormones cont. - Dosages for patients are often managed by salivary hormone levels. There is no scientific evidence that these are meaningful. - When counseling patients who have decided to use compounded HRT it is important to inform them that ACOG recommendations are to use an FDA approved preparation. It is also important to ensure awareness of the potential risks of compounded preparations.

TREATMENT OPTIONS FOR MENOPAUSAL SYMPTOMS – SYSTEMIC ESTROGEN Oral estrogens Conjugated equine estrogen

(Premarin)

Transdermal estrogens Avoid first pass effect – especially useful for women with moderate CHD risk factors, thrombophilia

Esterified Estrogens

(Menest)

Patches

Micronized 17-beta estradiol

(Estrace)

Synthetic conjugated estrogens

(Enjuvia)

(Alora,Climara,Menostar ,Minivelle,Vivelle,Vivelle Dot)

Topical Gels, Emulsions (Divigel, Elestrin, Estrasorb)

TREATMENT OPTIONS FOR MENOPAUSAL SYMPTOMS – COMBINED SYSTEMIC THERAPY Oral Estrogen + Progesterone

Transdermal Estrogen + Progesterone

CEE x 14 days, CEE + MPA x 14 days

(Premphase)

Estradiol/levonorgestrel

(Climara Pro) (Combipatch)

CEE + MPA

(Prempro)

Estradiol/norithindrone acetate

Estradiol, estradiol/norgestimate alternating

(Prefest)

Estradiol/norethindrone acetate

(Activella)

Norethindrone acetate/ethinyl estradiol

(Femhrt)

Estradiol/drosperinone

(Angelique)

TREATMENT OPTIONS FOR MENOPAUSAL SYMPTOMS – VAGINAL ESTROGENS • Useful for relief of genitourinary symptoms • Vaginal dryness • Vaginal itching, burning • Dysparunia • Dysuria • Urinary urgency and/or frequency

• Nocturia  Stress or urge urinary incontinence  All preparations have been shown to be equally effective

VAGINAL ESTROGENS 17 B estradiol

(Estrace vaginal cream)

Conjugated estrogens

(Premarin vaginal cream)

estrone

(Estragyn vaginal cream)

17 B estradiol

(Estring)

Estradiol acetate

(Femring)

Estradiol hemihydrate

(Vagifem)

OPTIONS FOR TREATMENT OF MENOPAUSAL SYMPTOMS – PROGESTERONES • Prevents increased risk of endometrial hyperplasia and malignancy in women with an intact uterus who are on systemic estrogen. • Available progesterones include: • Medroxyprogesterone Acetate or MPA (Provera)

• Micronized progesterone (Prometrium) • The Levonorgestrel- releasing IUD (Mirena) has also been used off label to prevent endometrial hyperplasia in women on systemic estrogen

OTHER OPTIONS FOR TREATMENT OF MENOPAUSAL SYMPTOMS • Duavee – Conjugated estrogens + bazedoxifene, a selective estrogen receptive modulator (SERM). An option for women who have severe symptoms from progesterone. Prevents endometrial hyperplasia. • Osphena – Option for dysparunia due to vaginal atrophy • Paroxitene – indicated for moderate to severe vasomotor symptoms

RISKS AND BENEFITS OF HRT  HRT is a safe option for symptomatic, healthy women within 10 years of menopause or younger than age 60 without contraindications to treatment  Common contraindications- history of breast cancer, CHD, previous VTE, stroke, active liver disease  WHI showed total mortality was reduced by 30% in women under 60 on HRT vs. placebo when analyzed separately. Other studies since then have shown similar findings.

RISKS AND BENEFITS OF HRT (WHI) E2/P2 vs. Placebo per 1000 women aged 5059 per 5 yrs HRT use

With E2/P2

E2 vs. Placebo per 1000 women aged 50-59 per 5 yrs HRT use

With E2

CHD

2.5 additional cases

CHD

5.5 fewer cases

Invasive breast cancer

3 additional cases

Invasive breast cancer

2.5 fewer cases

Stroke

2..5 additional cases

Stroke

.5 fewer cases

PE

3 additional cases

PE

1.5 additional cases

Colorectal cancer

.5 fewer cases

Colorectal cancer

.5 fewer cses

Hip fracture

1.5 fewer cases

Hip fracture

1.5 additional cases

All cause mortality

5 fewer events

All cause mortality

5.5 fewer events

SUMMARY • Thoroughly counsel women about risks, benefits and options, carefully assess risk factors • Do not be afraid of HRT in healthy postmenopausal women • For symptomatic women under age 60 you may be decreasing overall mortality and substantially improving quality of life.

REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

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