Menopause
Pooja H. Patel, Pharm.D.
Clinical Assistant Professor of Pharmacy Practice
PHAR 712 – IPT III
Learning Objectives
1. Define menopause and menopausal transition
(perimenopause).
2. List the common causes of menopause.
3. Identify the clinical presentation and diagnosis of menopause.
4. Compare and contrast the various medications used for
management of menopausal symptoms including, but not
limited to, their mechanisms of action, dosing regimen,
important adverse effects, and clinically important drug
interactions.
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Learning Objectives
5. Evaluate the risk and benefit of different hormone
replacement therapies as well as the non-estrogen therapies.
6. Summarize appropriate counseling (pharmacologic and non-
pharmacologic) for patients diagnosed with menopause.
7. Given a clinical situation, design an appropriate treatment
regimen for a patient experiencing menopausal symptoms
(including drug choices, drug doses, treatment duration, and
monitoring parameters).
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Menopause
Menopause:
• Permanent cessation of menses (12 consecutive months of
amenorrhea) following the loss of ovarian follicular activity
• Median age of onset ~51 years
Menopausal transition (or Perimenopause):
• Onset of irregular menses → 12 months after last menstrual period
• Late reproductive years ~late 40s
• Develops over a span of 4 to 7 years
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Etiology of Menopause
• Normal process of aging
• Ovarian surgery – hysterectomy ± oophorectomy
• Medications
• Pelvic irradiation
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Clinical Presentation of Menopause
• Vasomotor symptoms
• Genitourinary syndrome of menopause (GSM)
• Vulvovaginal atrophy (VVA)
• Urinary tract dysfunction
• Mood changes, anxiety, depressive symptoms
• Arthralgia
• Bone resorption → fractures
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Diagnosis of Menopause
 Clinical presentation
 Labs:
 FSH elevated (> 40 IU/L)
 Serum estradiol >90% decrease
 Other diagnostic tests:
 Thyroid function test
 Iron stores
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Goals of Treatment
 Natural process of aging – NOT a disease
 Improve quality of life → Symptom relief
 Vasomotor symptoms
 Urogenital symptoms
 Decrease long term risks
 Osteoporosis
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Treatment of Menopause
Treatment
Vasomotor
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Pharmacologic
NonPharmacologic
Genitourinary
Osteoporosis
Non-Pharmacologic Treatment of Menopause
 Layered clothing
 Lowering room temperature
 Exercise
 Decrease intake of hot spicy food, caffeine, and hot beverages
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Treatment of Menopause
Treatment
Vasomotor
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Pharmacologic
NonPharmacologic
Genitourinary
Osteoporosis
Pharmacologic Treatment – Vasomotor
 Hormone replacement therapy (HRT)
 estrogen alone or in combination with progestin
 Non-estrogen therapy
 SSRI
 SNRI
 clonidine
 gabapentin
 Alternative medicine
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Vasomotor – Hormone Replacement Therapy
General:
 Estrogen – mainstay of therapy
 Biological estrogens: estradiol > estrone > estriol (potency)
 Synthetic estrogen: ethinyl estradiol
 No uterus: Estrogen alone recommended
 Intact uterus: Estrogen + Progesterone (Progestin helps to avoid 5-to8-fold risk of endometrial adenocarcinoma)
 Progesterone ONLY for females that have a history of VTE
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Routes: oral or transdermal – patch, gel, cream, emulsion, spray
HRT– Agents
Drug
Brand name
Initial dose
Oral estrogens
CEE
Premarin
0.3 – 0.45mg
estradiol acetate Femtrace
0.45mg
micronized 17β Estrace
1mg
estropipate
Ortho-Est, Ogen 0.75mg
Synthetic CE
Enjuvia
0.3mg
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Usual dose
range
0.3 – 1.25mg
0.45 – 1.8mg
1 – 2mg
0.75 – 6mg
0.3 – 1.25mg
HRT– Agents
Drug
17β-estradiol
Brand name
Initial dose
(daily)
Transdermal estrogens
Vivelle, Alora,
0.025mg
Climara,Estraderm
Other topical forms of estrogen
Estrasorb
0.05mg
17β-estradiol
emulsion
17β-estradiol gel EstroGel, Elestrin
17β-estradiol spray Evamist
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0.5 – 1mg
3.06 – 4.59mg
Usual dose
range (daily)
0.025 – 1mg
HRT– Agents
Drug
Brand name
Dosage (daily)
Oral progesterone
medroxyprogesterone acetate Provera
5 – 10mg
micronized progesterone**
Prometrium
200mg
norethindrone acetate
Aygestin*
5mg
Combination – estrogen + progesterone (DiPiro)
*Not approved for postmenopausal hormone therapy in the US
**Use of micronized progesterone is considered safer alternative
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HRT – Considerations
Considerations:
 Standard dose vs. low dose vs. ultra-low dose
 Use the lowest dose for the shortest amount of time
 Continuous cycle vs. continuous long cycle vs. continuous combined
vs. intermittent combined
 Discontinuation of HRT
 Duration of treatment
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HRT – Adverse Effects
 Estrogen: nausea, breast tenderness, vaginal bleeding, and
headaches, stomach cramps, bloating, and hair loss
 Progestins: weight gain, irritability, depression, dizziness, bloating,
headaches, and fatigue
 Endometrial cancer
 Breast cancer
 Thromboembolic risk
 Cardiovascular events
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HRT – Contraindications

↑
 Undiagnosed abnormal genital bleeding
 Breast cancer, known, suspected or h/o
 Estrogen-dependent neoplasia
 Venous thromboembolism
 Arterial thromboembolic disease
 Liver dysfunction or disease
 Pregnancy
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Vasomotor – Non-Estrogen Therapy
SSRI/SNRI
 Paroxetine – only agent FDA approved for vasomotor symptom treatment
(7.5mg once daily)
 Adverse effects: nausea, dizziness, dry mouth, nervousness, constipation,
somnolence, sweating, sexual dysfunction
Clonidine: 0.1 to 0.2mg once daily
 Adverse effects: Dry mouth, insomnia, drowsiness
Gabapentin: 300 – 1200mg once daily
 Adverse effects: dizziness, somnolence, peripheral edema
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Complementary Medicine
 Phytoestrogens
 Herbal medicine
 Black cohosh, ginseng, St. John’s Wort, ginkgo biloba, Chinese
herbal medicine
 Vitamin E
 Alternative techniques
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Treatment of Menopause
Treatment
Pharmacologic
Vasomotor
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Genitourinary
NonPharmacologic
Osteoporosis
Pharmacologic Treatment – Genitourinary
 Hormone replacement therapy (HRT)
 estrogen (systemic or local)
 Non-estrogen therapy
 ospemifene
 vaginal lubricants
 vaginal moisturizers
 Herbal remedies
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HRT – Agents
Drug
estradiol acetate ring
CEE vaginal cream
17β estradiol cream
17β estradiol ring
estradiol vaginal insert
estradiol hemihydrate
tablet
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Brand name Initial dose Dose range
Vaginal estrogens
Femring
0.05mg
0.05 – 0.1mg
Premarin
0.5 – 2g
Estrace
0.1mg
Estring
0.0075mg
Imvexxy
2 – 4g
Vagifem
10mcg
10 – 25mcg
Vasomotor – Non-Estrogen Therapy
Ospemifene
 Estrogen agonist and estrogen antagonist
 Dose: 60mg once daily
 Adverse effects: hot flashes, vaginal discharge, muscle spasms, genital
discharge, excessive sweating
Vaginal lubricants
Vaginal moisturizers
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HRT – Considerations
Considerations:
 Local estrogen therapy – preferred over systemic therapy
 Other menopausal symptoms – consider systemic estrogen therapy
 Consider non-estrogen therapy with vaginal lubricants/moisturizers
prior to hormone therapy for patients with only genitourinary
symptoms
 Patient specific therapy
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Treatment of Menopause
Treatment
Pharmacologic
Vasomotor
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Genitourinary
NonPharmacologic
Osteoporosis
Summary
 Menopause is the permanent cessation of menses for 12
consecutive months following the loss of ovarian follicular activity
 Vasomotor symptoms are best managed with systemic hormone
therapy
 Vaginal symptoms are best treated with systemic or topical hormone
therapy, but topical methods are preferable d/t fewer adverse
effects.
 Systemic hormone therapy should be given at lowest dose for
shortest time to decrease the risk of serious adverse events
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References
 Kalantaridou SN, Dang DK, Calis K. Chapter 65. Hormone Therapy in Women. In: DiPiro JT,
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Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds.Pharmacotherapy: A Pathophysiologic
Approach, 10e New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com.libezproxy.tamu.edu:2048/content.aspx?bookid=689&sectionid=45310518.
Cobin RH and Goodman NF. American Association of Clinical Endocrinologists and American
College of Endocrinology Position Statement on Menopause – 2017 Update. Endocrine Practice
2017;23(7):869-880.
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(11):3875-4011.
Clinical management guidelines of robstetrician-gynecologists. Management of menopausal
symptoms 2014;123:202-216.
Goodman NF, Cobin RH, Ginzburg SB, et al. American association of clinical endocrinologists
medical guidelines for clinical practice for the diagnosis and treatment of menopause
2011;17(6):1-17.
Hill DA and Crider M. Hormone therapy and other treatments for symptoms of menopause. Am
Fam Physician 2016;94(11):884-89.
Questions?
Pooja H. Patel, Pharm.D.
Clinical Assistant Professor of Pharmacy Practice
phpatel@tamu.edu