1. Post menopausal Hormone replacement
Dr. Jonathan Ruby
Assistant Residency Director
Lake Cumberland Family Medicine Residency Program

2. Nothing to disclose unfortunately

3. Theresa W. Patient is 49 year old who comes in to establish care.
She is experiencing nightly hot flashes that interfere with sleep.
Patient requests “hormones”
Her last menstrual period was over a year ago.
She has no chronic medical conditions.
No history of hypertension/VTE/migraines
She smokes 1 ppd
Last PAP was in 2005, normal with no history of dysplasia
She has never had a mammogram

4. Diagnosis of menopause
Mean age is 51 with 95% of women menopausal at years
Women > 45 years
Irregular menstrual cycles
Menopausal symptoms (hot flashes, mood changes, sleep disturbances, etc)
No further diagnostics necessary
FSH may be misleading if still having irregular menses
However, if patient is looking for reassurance or sexually active with no reliable birth control use or clinical features of thyroid disease or hyperprolactinemia consider:
FSH (>25 IUL/ml indicative of menopause)
TSH, prolactin, HcG may also be reasonable

5. Diagnosis of menopause
Women between years of age
If patients are having irregular menstrual cycles, with or without menopausal symptoms
Recommend checking:
FSH
TSH
Prolactin
Women less than 40
Will need workup for premature ovarian failure

6. Diagnosis of menopause
Special considerations:
Contraception use
OCP’s in non-smoking women have been found to be safe up to age 50
Recommend checking FSH. If >25 IU/L, highly suggestive of menopause. But no value diagnostic
Post hysterectomy/endometrial ablation
FSH > 25 IU/L suggest transition to menopause

7. Theresa W. Patient is 49 year old who comes in to establish care.
She is experiencing nightly hot flashes that interfere with sleep.
Patient requests “hormones”
Her last menstrual period was over a year ago.
She has no chronic medical conditions.
No history of hypertension/VTE/migraines
She smokes 1 ppd
Last PAP was in 2005, normal with no history of dysplasia
She has never had a mammogram

8. Indications for Hormone Replacement therapy (HRT)
Management of menopausal symptoms
Vasomotor symptoms (hot flashes)
Mood liability/depression
Vaginal atrophy
AKA-Genitourinary syndrome of menopause
Joint aches and pains

9. NOT Indications for HRT
Not for prevention of cardiovascular heart disease (CHD)
Not for prevention of osteoporosis
Not for treatment or prevention of cognitive decline/dementia

10. Contraindications for HRT
Breast cancer
CHD
Previous thromboembolic event
Active liver disease
Unexplained vaginal bleeding
High risk endometrial cancer
Transient ischemic attacks

11. Theresa W. Patient is 49 year old who comes in to establish care.
She is experiencing nightly hot flashes that interfere with sleep.
Patient requests “hormones”
Her last menstrual period was over a year ago.
She has no chronic medical conditions.
No history of hypertension/VTE/migraines
She smokes 1 ppd
Last PAP was in 2005, normal with no history of dysplasia
She has never had a mammogram

12. Benefits of hormone replacement
Decrease in mortality of nearly 30%
for women age 50-59
Decrease osteoporotic fractures
Reduce the risk of Type II diabetes
Moderate improvements in mental health and well being
60% reduction in cataract formation

13. Risks for hormone replacement
Women’s health Initiative clearly demonstrated increased risks in the older menopausal patient > 60 years of age
Coronary Heart disease
related to progestin
no increase seen in unopposed estrogen
risk is less if <60years

14. Risks for hormone replacement
Stroke
30% increased risk of ischemic stroke
Venous thromboembolism (VTE)
Gallbladder disease
Breast cancer
No increase and possible a decrease with unopposed estrogen
felt to be related to progestin

15. Risks of HRT-combined estrogen/progesterone
•Coronary heart disease (CHD) – 2.5 additional cases
•Invasive breast cancer – 3 additional cases
•Stroke – 2.5 additional cases
•Pulmonary embolism – 3 additional cases
•Colorectal cancer – 0.5 fewer cases
•Endometrial cancer – no difference
•Hip fracture – 1.5 fewer cases
•All-cause mortality – 5 fewer events
Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015

16. Risks of HRT-Estrogen only
•CHD – 5.5 fewer cases
•Invasive breast cancer – 2.5 fewer cases
•Stroke – 0.5 fewer cases
•Pulmonary embolism – 1.5 additional cases
•Colorectal cancer – 0.5 fewer cases
•Hip fracture – 1.5 additional cases
•All-cause mortality – 5.5 fewer events
Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015

17. Theresa W. Patient is 49 year old who comes in to establish care.
She is experiencing nightly hot flashes that interfere with sleep.
Patient requests “hormones”
Her last menstrual period was over a year ago.
She has no chronic medical conditions.
No history of hypertension/VTE/migraines
She smokes 1 ppd
Last PAP was in 2005, normal with no history of dysplasia
She has never had a mammogram

18. Starting Estrogen Route Oral
Greater effect on liver due to first pass effect
More favorable effect on lipid profile - EXCEPT triglycerides
Increases Sex Hormone Binding Globulin (SHBG)/Triglycerides/HDL/clotting factors
Preparations
Conjugated equine estrogens (Premarin)
17-beta estradiol (micronized)
Esterified estrogens (Menest)
Ethinyl estradiol (OCP’s)
Estropipate (Ortho-Est)

19. Starting Estrogen Route Transdermal
Lower incidence of VTE and stroke (compared or oral route)
More favorable lipid profile (compared to oral route)
50 mcg/day equivalent to oral conjugated estrogens
Topical
Gel preparations dosed in metered dose pumps (1.25 gm/day, delivers 0.75mg estradiol/day)
Gel packets (estradiol 0.25mg, 0.5mg and 1.0mg / day)
Topical spray (1.53mg estradiol/day)
caution around children/pets

20. Starting Estrogen Route Vaginal
Effective at low doses for management of vaginal atrophy
(now called Genitourinary Syndrome of Menopause, GSM)
Preparations
Vaginal cream (Premarin, Estrace cream)
Vaginal tablet (Vagifem, Yuvafem)
Vaginal rings (Femring, Estring)-good for 3 months

21. Progesterone Must have on board in women with intact uterus
Medroxypregesterone acetat (MPA) is most common
Can dose cyclically (5-10mg a day) or continuously ( mg/day)
Progesterone
Little impact on lipids
Dose Cyclic (200mg/day X 12 days) or continuous (100mg/day)

22. Progesterone Levonorgestrel-releasing intrauterine device
Not approved in US for endometrial protection in menopause
but being used overseas and some are using it off label
Bazedoxifene-Evista
selective estrogen receptor modulator (SERM)
"progestin-free" MHT for women with a uterus
Increased risk for VTE

23. Combination estrogen-progestin
Oral Preparations
Oral conjugated equine estrogen/medroxyprogesteron (Prempro)
Oral conjugated equine estrogen/ bazedoxifene (Duavee)
estradiol/norgestimate (Prefest)
estradiol/norethindrome (Activella, Amabelz, Mimvey)
estradiol/drospirenone (Angeliq)
ethinyl estradiol/norethindrone (FemHRT, Jevantique Lo)

24. Combination estrogen-progestin
Transdermal Preparations
0.045mg estradiol/0.015mg levonorgestrel-Climara Pro
0.050mg estradiol/0.14mg norethindrone - Combipatch

25. References
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.
Worzala K, Hiller R, Sperduto RD, et al. Postmenopausal estrogen use, type of menopause, and lens opacities: the Framingham studies. Arch Intern
Baker VL. Alternatives to oral estrogen replacement. Transdermal patches, percutaneous gels, vaginal creams and rings, implants, other methods of delivery. Obstet Gynecol Clin North Am 1994; 21:271.
Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 100:3975
ACOG Practice Bulletin No. 141: management of menopausal symptoms. Obstet Gynecol 2014; 123:202.
Nelson HD, Walker M, Zakher B, Mitchell J. Menopausal hormone therapy for the primary prevention of chronic conditions: a systematic review to update the U.S. Preventive Services Task Force recommendations. Ann Intern Med 2012; 157:104.