You are on page 1of 55

Menopause / Hormone Replacement

Disclosure Statement

Jennifer Keehbauch, MD is a trainer for Merck Nexplanon

Learning Objectives
1. Counsel post-menopausal women regarding the risks and
benefits of pharmacologic and non-pharmacologic options for
the relief of menopausal symptoms.
2. Assess patients’ current use of nutritional, herbal or dietary
supplements for the relief of menopausal symptoms and
provide counseling to encourage safe and effective use.
3. Educate patients regarding their increased risk of coronary
artery disease and osteoporosis following menopause and how
to take preventive measures, including diet and exercise.
4. Differentiate specific issues, disease processes, and treatments
based on ethnicity, gender and genetics.
• Menopause is a natural event defined as 12 months of amenorrhea with no
obvious pathologic cause.

• Perimenopause is the lay term encompassing the menopause transition and the
first 12 months after the final menstrual period (FMP).

• Estrogen Therapy (ET) is unopposed estrogen for postmenopausal women without

a uterus.

• Estrogen-Progestogen Therapy (EPT) is a combination of estrogen and

progestogen (either progestin or progesterone).

• Hormone Therapy (HT) encompasses both ET and EPT.

Stages of Menopause Highest prevalence of
menopausal Menopause

Journal of Clinical Endocrinology and Metabolism, Executive Summary of the Stages of Reproductive, April 2012, 97(4):1159-1168,
What is the most common age range for US women to
experience menopause?

A. Age 38 to 45 years
B. Age 55 to 60 years
C. Age 52 to 59 years
D. Age 45 to 55 years
E. Age 42 to 48 years
Menopause would most likely occur at an earlier than
average age in which woman?

A. One who smokes 2 packs of cigarettes per day

B. One who has had 3 children
C. One who has a 10-year history of oral contraceptive use
D. One whose mother entered menopause at age 56
E. One whose body mass index is 30 kg/m2
Risk factors for Earlier Menopause
• Smoking (up to 2 years)
• Nulliparous
• Hysterectomy
• Fragile X carrier
• Autoimmune disorder
• Living at high altitude
• Exposure to chemo/radiation
Premature or Early Menopause
• Menopause before age 40-45 years
• Less than 1% of women
• Etiologies:
◦ Most commonly idiopathic
◦ Fragile X
◦ Radiation Exposure: > 500 rads
• Treatment: HRT until age 51 for bone preservation
BMJ 2012;344:e763
Decreasing Estrogen Levels
• Thermoregulatory set point lowered
• Serotonin levels decreased
• Thinning of vaginal epithelium
• Thinning of urethral epithelium
• Decreased blood flow to vagina/vulva

Psychiatr Clin N Am 33 (2010)

Symptoms of Menopause
Physical Changes Intangible Changes
• Vasomotor symptoms • Depression
• Vaginal dryness • Breast Pain
Common in early menopausal transition
• Sexual dysfunction
• Sleep disturbances
• Urinary incontinence
• Memory loss
• Bone loss
• Skin changes
Racial/Ethnic Differences in Menopausal
•Caucasian women report more psychosomatic symptoms
•African American women report more VMS
•Japanese and Chinese women report fewer symptoms

Soc Sci Med 2001;52(3):345–356

• History:
– 12 consecutive months of amenorrhea
– Average age 51

• Diagnostic labs not indicated

A 51-year-old woman has frequent and
distressing hot flushes that interfere with her
work and sleep, and vaginal dryness that makes
sexual intercourse with her husband
uncomfortable. She is otherwise healthy. How
should her case be managed?
Menopause Treatment Discussion
• incorporate the woman’s health and QOL priorities
• personal risk for VTE, CHD, CVA , and breast ca
• Hormone therapy (HT)
• Non-hormone therapy
• “Bioidentical HT”

With Hormone Therapy,

a woman’s “breasts and
genital organs will not
shrivel. She will be much
more pleasant to live with
and will not become dull
and unattractive.”

The Evidence in the 1990’s
Can start HRT at any time:
◦ Cardioprotective
◦ Delayed Alzheimers
◦ Reduced Colon Cancer
◦ Prevented Macular
USPSTF Recommendation
• USPSTF recommends against routine use of Estrogen
or Combined HT for prevention of chronic conditions
• Based on meta-analysis of 9 studies, primarily from: the
Women's Health Initiative (WHI) and the Heart and
Estrogen/Progestin Replacement Study (HERS) LOE:1A
Ann Intern Med 2012
USPSTF Absolute Numbers
per 10,000 users per year
Combined HT Estrogen Only
Fractures 46 less 56 less
Breast cancer 8 more none
Stroke 9 more 11 more
DVT/PE 21 more 7 more
Dementia 22 more none
Death none 2 less
Criticism of HERS and WHI trials
• HERS – average age 67, with known CHD
◦ 75% new users to hormones
• WHI – average age 63
◦ 36% on anti-hypertensives, 20% on aspirin

• Both trials used 0.625 mg conjugated estrogens alone or

with 2.5 mg medroxyprogesterone acetate per day for less
than 5 years
JAMA 1998; 280: 605-613
JAMA 2002;288:321–33.
Hum. Reprod. (2003) 18 (10): 1992-1999
Effect of HRT on CV Events in Recently Post-
Menopausal Women
• 10-year randomization on 2016 healthy women with
mean age of 49.7
• Reduced risk of death with up to 10 years use (RR 0.61
• NO increase risk of thromboembolism or breast cancer
(RR 0.90, p=0.72) or other cancers (RR1.21, p=0.35)
BMJ 2012 344e763
Summary of Evidence for
All-Cause Mortality
Meta-analysis of
Observational data
0.60 0.40-0.80

HERS 1.10 0.92-1.31

WHI (ERT) 0.63 0.32-1.24
WHI (HRT) 1.08 0.75-1.55
DOPS 0.61 0.39-0.94
An App for Menopause
•The North American Menopause
Society (NAMS) has released a free
mobile app
•For Physicians or Patients
•Input patient data and preferences and
it recommends hormonal and non-
hormonal options
Management of VMS
• HRT is the most effective treatment for severe hot
flushes (LOE=1A)
– Transdermal or transvaginal route should be considered

• Therapy with progestins, SSRIs, or gabapentin is

suggested as alternatives
Complementary and Alternative Medicine (CAM)
•80% of women in the SWAN study used CAM

•Common forms of CAM: vitamins, dong quai, soy, black

cohosh, red ginger, acupuncture, and relaxation

Menopause. 2007 Jul-Aug;14(4):612-23

Contraindications for HRT
• Unexplained vaginal bleeding
• Hormone sensitive cancers
• Past history of thromboembolus
• Hypertriglyceridemia
• Chronic liver disease
• Active or Recent Stroke or AMI
What is the most prevalent menopausal symptom
reported by US women?

A. Genitourinary atrophy
B. Depression
C. Insomnia
D. Hot flush
E. Headache
Vasomotor Symptoms
•Moderate to severe VMS affects 50% of women
•VMS typically last 7.4 years
–Range 3.4-11.8 years
–Lasts longer in African American women (10.1 yrs)
–Symptoms persist in 10-15% women

JAMA Inter Med 2015;175(4):531-539

NEJM 2006;355:2338-47
North American Menopause Society (NAMS)
Recommends Lifestyle Changes
◦ Avoid Triggers: spicy food, alcohol, caffeine
◦ Keeping core body temperature cool
◦ Lower AC, light clothing, fan at night
• Weight loss
• Exercise, relaxation therapy & stress management
alone not effective
NAMS Menopause Practice, A Clinician’s Guide 2010;
Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD006108
Candidates for Nonhormonal Therapies
•Treatment Naïve
•OTC remedy failures or minimal effect
•Cannot or choose to not use HT
•Desire or need to discontinue HT
Which of the following is effective for post-menopausal hot
A. Dong Quai
B. Venlafaxine
C. Soy
D. Clonidine
E. St John’s Wort
Treatment of Hot Flushes
Most Possibly NOT effective or not
Effective Effective indicated
Estrogen Venlafaxine Clonidine Dong Quai
(85-95%) (60-65%) Black Cohosh SERMS(NI)
Progesterone Phytoestrogens
Paroxetine (soy)
Gabapentin Red Clover
St John’s Wort

Obstet Gynecol 2014 Jan;123(1); 202-216

Which of the following conditions is an absolute contraindication
to hormone replacement therapy?

A. Poorly controlled hypertension

B. Undiagnosed genital bleeding
C. History of thromboembolic disease
D. Migraines
E. Gallbladder disease
Estrogen-Only Preparations for Women
Without a UTERUS
Estrogen Medication Route
Standard doses: Conjugated Premarin PO, Vaginal
0.625 mg conjugated equine est Synthetic Enjuvia PO
1 mg micronized 17-beta estradiol Esterified Menest PO

50 mcg/day transdermal 17-β-est

1.25 mg piperazine estrone sulfate Estrace PO/Vaginal
Climara Patch
Consider starting at lower doses
Vivelle/dot Patch
(0.3 mg conjugated estrogens or 0.5 17-β Estradiol Estrogel Gel
Divigel Gel
mg estradiol) Evamist Spray
Depo-Estradiol Injectable
Estrogen-Progestin Combinations for Women Who Have a Uterus
Estrogen/Progestin Medication Route
Femhrt, Jinteli,
Ethinyl Estradiol & Norethinedrone PO Transdermal
Activella, Lopreeza,
17-β Estradiol & Norethinedrone PO
17-β & Levonorgesterol Climara Pro Transdermal
Premphase PO
Prempro PO
Estrogen/SERM Medication Route

CEE/Bazedoxifene Duavee PO
Role of Transdermals
• Transdermal estrogen may have a lower risk of VTE and
◦ Doesn’t increase triglycerides or HDL
◦ Have less nausea
• May be preferred for women with:
◦Gallbadder disease
BMJ 2012;344:e763
Climacteric: J of InternMeno Soc: 2010;13:429-32.
Perimenopausal Women
• Low dose OCPs can be used in lean, healthy,
non-smoking women
• Benefits:
◦ Decrease vasomotor symptoms
◦ Restore predictable bleeding pattern
◦ Enhance BMD
• Once 50-yo, discuss stopping OCP
◦ consider changing to postmenopausal regimen if necessary for sx
BMJ 2012;344:e763
Summary: HRT for Hot Flashes
• The lowest effective dose of ET should be prescribed
• Duration of treatment dictated by clinical needs and
safety monitoring
• Stopping or tapering of HRT will cause recurrence of
symptoms in 50% of women
• Vaginal bleeding within 6 months of initiating HRT
does not need investigation
BMJ 2012;344:e763.
Vaginal Symptoms
Esrogen Treatment Most Effective for Vaginal
Symptoms (1B)
•Local vaginal therapy highly effective for treating atrophy
– Success rates > 80%
•Controversial in women with hx of breast cancer
•NO concomitant progestogen therapy required
– But no long-term safety trials
•Formulations vary: Beware FEMring (estradiol acetate) delivers
systemic dose

2012 Mar;19(3):257-71.
Atrophic Vaginitis Treatment Options
Creams Ring Vagitories Vaginal Tablets

Premarin Estring Ortho Gynest Vagifem

Conjugated Releases Vaginal estriol (Estradiol) vaginal
equine estrogens estradiol in a suppositories estrogen tablet
(CEE) consistent
manner over 90
Estrace days Not currently
Estradiol cream available in the
United States
Retail ~ $300 Retail ~ $300 Retail ~ $200
Affordable Topical Estrogen ~ $4
• Vaginal Estrogen needed is ~ 0.1mg
• Can use compounded doses at Walgreens 0.075 or 0.15
• Can use ¼ tab of Estrace 0.5 mg (0.125 mg) PV qhs for 2
weeks, then 1-3 times a week
SERM for Vulvar Vaginal Atrophy
• Ospemifene (Osphena) 60 mg po daily
• Selectively stimulates vaginal tissue, bone
• Does not stimulate endometrium
• Does not stimulate breast tissue
• Side effects may include hot flashes and thrombosis

Prescriber's Letter. June 2013; 29

Int J Womens Health. 2013 Sep 25;5:605-611
Non-Hormonal Treatment Options for Vaginal Symptoms
• Lubricants:
◦ Water-based: Slippery Stuff, Astroglide, KY Jelly
◦ Silicon-based: ID millennium, PINK
◦ Oil-based: Elegance Women’s Lubricant (not compatible
with condom)
• Moisturizers: intended for use one or more times per week
not just during sexual activity
◦ Replens, Me Again, Vagisil Feminine Moisturizer,
Feminease, KY SILK-E
Does testosterone increase libido in postmenopausal women?
• Transdermal Testosterone increases libido in women (LOE=1b)
• No medication approved by the FDA
• Canada/UK approved 300 mcg patch daily
• Long-term safety unknown

“We continue to recommend against making a diagnosis of androgen deficiency

syndrome in healthy women because there is a lack of a well-defined syndrome,
and data correlating androgen levels with specific signs or symptoms are
unavailable.” Endocrine Society

J Clin Endocrinol Metab. 2014 Oct;99(10):3489-510; AAFP Essentials 2012;

Hormone Therapy for Sexual Function in
• HT with estrogen alone or combined
estrogen/progesterone produces small to moderate
improvement in symptomatic women within 5 years of
• Unable to assess effect of SERMS or synthetic steroids

Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD009672.

Filbanserin (Addyi) – pink Viagra
To be able to prescribe Addyi, prescribers must be trained, successfully complete a
knowledge assessment, and enroll to be certified in the Addyi REMS program.
Does it work?
◦ No difference in reported sexual desire
◦ 0.5-1 more “satisfactory” sexual events per month

Side-effects: hypotension, fatigue and somnolence

Contraindications: Alcohol, liver disease, P450 inhibitors

JAMA Intern Med. 2016 Feb 29
“Bioidentical Hormones” or
Compounded Hormones
• No scientific or medical evidence supports the use of non-
FDA “bioidentical hormones”
• NOT subject to FDA oversight
– Inconsistent dose and purity
• Salivary hormone levels do not correlate with plasma levels
DHEAS for Peri- or Postmenopausal Women
• Does not improve quality of life
• Associated with increased acne 15% vs 3%
• Slightly improves sexual function compared to placebo
• DHEA was not superior to HT for sexual function

Cochrane Database of Systematic Reviews 2015, Issue 1. Art. No.:


Use of SERMS for Treatment
• Tamoxifen for prevention and treatment of breast
• Raloxifene (Evista) for prevention and treatment of
osteoporosis and invasive breast cancer
• Ospemifene for dyspareunia
• Bazedoxifene with CEE to prevent breast or endometrial
J Steroid Biochem Mol Biol. 2013 Dec 25
Summary for HRT Use
• Individualize therapy based on patient’s unique benefit
and risk profile
• Safe in healthy, perimenopausal women
(50-60 years)
• Hormones should be prescribed at the lowest effective
doses and shortest duration
• Do not use for the prevention of chronic disease
• Reevaluate annually
Thank you!