The Current Pharmacological Treatment of Peri

The Pharmacological Management of
Peri-Menopause and Menopause
Debora Bear, FNP, MSN, MPH
University Of New Mexico Hospital
Hormones and other Treatments
Disclosure Statement
•  I have no real or perceived vested interests that relate to this
presentation nor do I have any relationships with pharmaceutical
companies, biomedical device manufacturers, and/or other
corporations whose products or services are related to pertinent
therapeutic areas.
Objectives:
1. Describe the most common medical issues associated with
menopause
2. Apply the scientific evidence regarding the risks and
benefits of medical therapies as well as risks and benefits of
alternative treatments
Case study:
63 year old woman requests a refill of her “bio identical
hormone” prescription. She takes this for her duodenitis,
tendon pain, urinary incontinence, skin, hot flashes (she has
tried EVERYTHING else and it is the ONLY thing that
works), memory, leg swelling, varicose veins, bloating (had
terrible IBS prior), osteopenia, and vaginal dryness.
Does not get mammograms due to concern for “radiation
exposure”.
Describe the most common medical issues associated with
peri-menopause and menopause
When is menopause
Premature
< 40 (1%),
•  For women who miss three or more consecutives menses, measure
HCG, FSH, estradiol, prolactin, TSH
•  Consider AMH level, vaginal ultrasound, Karyotype and testing for
fragile x permutation, thyroid peroxidase antibodies, adrenal
antibodies, fasting glucose, serum calcium and phosphorus levels
•  If not contraindicated: consider estrogen treatment
early
< 40 < 45 (5%)
median age 52
Describe the most common medical issues associated with
peri-menopause and menopause •  Contraception
•  Need for use until 12 months after FMP
•  Vasomotor Symptoms/
•  60%-85% (varies by culture): treat with
hormone replacement, SSRIs and SNRIs, CBT
•  Mood
•  Vaginal
•  Bone
•  Systemic replacement may not impact
•  Estrogen & decreased risk of hip fracture
•  Other: cardiovascular, memory,
cancer
•  Estrogen & stroke risk, memory not improved
with HRT?
•  Unopposed estrogen associated with endometrial
cancer, Selective Estrogen Receptor Modulators
decrease breast cancer
Contraception During Peri-Menopause
Methods
Key Points:
-CHC (Pills/Patch/Ring)
•  Review Medical Eligibility Criteria
-Progestin Only
•  Option to treat hot flashes
•  When to use/when to remove
-LARC
-Barrier Methods
•  Femcap, Diaphragm, condoms
Other Benefits from
Hormonal Contraception
•  Treats irregular uterine bleeding, reduce
vasomotor symptoms, decrease ovarian
and endometrial cancer, maintain bone
mineral density
Contraception: Case Study
A Fifty two year old woman presents for
her “annual”. She is on a CHC and has
menopause questions.
Treatments for Vasomotor Symptoms
•  Hormones
• 
Estrogen most effective treatment
•  Contra-indications (heart disease, breast cancer, active liver
disease, thromboembolic disease)
•  Shortest duration (< 4 yrs)
•  Low dose: < 0.3mg CE, < 5mg oral micronized estradiol < 0.25
µg transdermal estradiol, or < 0.25 µg ethinyl estradiol
•  Progestogen required for women with a uterus
• 
FDA-Paroxetine(SSRI) 7.5mg-25mg (not w/Tamoxifen)
• 
Venlafaxine XL(SNRI) 37.5, 75, 150mg
• 
900mg
• 
0.05-0.15mg
• 
Studies are poor to good showing these are not effective more
than placebo
Acupuncture
• 
May help some women
Behavioral
• 
May provide relief when done for 20min 3xa day
•  SSRI/SNRI
•  Gabapentin
•  Clonidine
•  Others:
Isoflavones
Botanicals
Beliefs about what is “Natural”
•  Natural= Believed to be
plant derived, not
synthesized. Made
without chemicals.
•  Associated with fewer or
no risks or adverse
effects. It is equally or
more effective than
conventional hormone
therapy
•  Treats & prevents
osteoporosis & has no
heart disease risk
•  Fewer than 1 in 3 women choose
to take conventional hormone
treatment
•  At least 36% of Americans use
some form of complementary/
alternative medicine (> 60% if
prayer & megavitamins for
health factored in)
•  The media, and not women’s
healthcare practitioners, have
been the primary source of
information concerning hormone
benefits and risks
•  The end product,
physiologic effect, should
be the concern
What are Bioidentical Hormones
•  Claim to Individualize
therapy based on hormone
levels
•  Diosgenin extrated from
high-yield soy and Mexican
yams (Dioscorea) and
chemically converted into
progesterone
• 
•  History: 1930s the first
BH preparations were both
natural and bioidentical,
they were derived from
human pregnancy urine
Saliva tests provide poor reproducibility,
lack evidence supporting the stability of
samples in storage and handling, and are
subject to large interassay variability.
Hormone levels in saliva may vary
depending on diet, time of day, the
hormone being tested, and changes in
other variables such as secretion rate.
• 
Much of the physiological effects are
determined at the cellular level and not
the sera level
• 
High failure rate of compounded progestin
which is solely prescribed to protect
women from estrogen-associated effects
on endometrial tissue
•  Estriol (biest/triest):
currently component in
most BHT. Considered by
proponents to be “gentler
and protective”
Table 1. Common Hormone Therapies for Relief of Menopausal Related Symptoms
Generic Brand Name Available generic Strength (mg) Route of Administration Indications Dosing Source of active ingredients FDA approved Bioidentical Branded hormone therapeutics Estrogen alone Conjugated estrogens Genestin No 0.625 0.9 Oral Moderate-­‐severe VmS Continuous daily Synthesized from soy and yams Yes No Conjugated synthetic estrogens Enjuvia No 0.3 0.45 0.625 1.25 Oral Moderate-­‐severe VmS Continuous daily Synthesized from soy and Mexican yams Yams Yes No 0.3 0.45 0.625 0.9 1.25 Oral Moderate-­‐severe VmS; moderate-­‐
severe vulval and vaginal atrophy Continuous daily Pregnant mares’ urine Yes No 0.625 Vaginal cream Atrophic vaginitis; kraurosis vulvae Conjugated estrogens Premarin No Esterified estrogens (estrone, equiline) Menest No 0.3 0.625 1.25 2.5 Oral Moderate-­‐severe VmS; atrophic vaginitis; kraurosis vulvae Continuous daily Synthesized from soy and yams Yes No Micronized estradiol (estrone, equiline) Estrace Yes 0.5 1 2 Oral Moderate-­‐severe VmS; atrophic vaginitis; kraurosis vulvae Prev.o st. Continuous daily Synthesized from soy and yams Yes Yes Estropipate Ogen Yes 0.625 1.25 2.5 Oral Moderate-­‐severe VmS; moderate-­‐severe vulvar and vaginal atrophy; Prev.o st. Continuous Synthesized from Mexican yams Yes Yes Estropipate Ortho-­‐Est Yes 0.625 1.25 Oral Moderate-­‐severe VmS; moderate-­‐severe vulvar and vaginal atrophy; Prev.o st Continuous Synthesized from yams Yes Yes Estradiol Alora No 0.025 0.05 0.075 0.1 Transdermal patch Moderate-­‐severe VmS; moderate-­‐severe vulvar and vaginal atrophy; Prev.o st Continuous Twice weekly Synthetic? Yes Yes Estradiol Climara No 0.025 0.0375 0.05 0.06 0.075 0.1 Transdermal patch Moderate-­‐severe VmS; moderate-­‐severe vulvar and vaginal atrophy; Prev.o st Continuous Once weekly Synthesized from soy Yes Yes Table 1. Common Hormone Therapies for Relief of Menopausal Related Symptoms Generic Brand name Available generic Strength (mg) Route of administration Indications Dosing Source of active ingredients FDA approved Bioidentical Estradiol Estraderm No 0.05 1 Transdermal patch Moderate-­‐severe Vms; moderate-­‐severe vulvar and vaginal atrohophy; Prev. o st. Continuous twice weekly Synthesized from Mexican yams Yes Yes Estradiol Estring No 2 delivers 7.5μg/day Vaginal ring Moderate-­‐severe vulvar and vaginal atrhophy Continuous q90 days Synthesized from Mexican yams Yes Yes Estradiol Vivelle Vivelle-­‐
Dot No 0.025 0.0375 0.05 0.075 0.1 Transdermal patch Moderate-­‐severe Vms; moderate-­‐severe vulvar and vaginal atrohophy; Prev. o st. Continuous twice weekly Synthesized from Mexican yams Yes Yes Estradiol acetate Femring No 0.05 0.01 /day Vaginal ring Moderate-­‐severe VmS Continuous q3-­‐
months Synthesized from soy Yes Yes (prodrug converts to estradiol) Estradiol acetate Femtrace No 0.45 0.9 1.8 Oral Moderate-­‐severe VmS Continuous Synthesized from soy Yes Yes (prodrug converts to estradiol) Estradiol cypionate Depo-­‐
Estradiol Yes 1 5 Injection (in oil) Moderate-­‐severe VmS Continuous Q3-­‐4 weeks Cyclic Synthetic? Yes Yes (prodrug converts to estradiol) Estradiol hemihydrate Estrasorb No 8.7 (two 1.74-­‐g pkgs) deliver 0.5/day Topical emulsion (micellar nanoparticle) Moderate-­‐severe VmS Continuous daily Synthesized from soy Yes Yes Estradiol hemihydrate Vagifem No 0.025 Vaginal tablet Atrophic vaginitis Continuous daily for 2 weeks twice weekly after Synthesized from soy Yes Yes Estradiol valerate Delestroge
n Yes 1 5 Injection (in oil) Moderate-­‐severe VmS Continuous q4 weeks cyclic Synthetic? Yes Yes (prodrug converts to estradiol) Estradiol valerate Valergen-­‐ 10,20, or 40 Yes 10 20 40 Injection (in oil) Moderate-­‐severe VmS Continuous q4 weeks cyclic Synthetic Yes Yes (prodrug converts to estradiol) Table 1. Common Hormone Therapies for Relief of Menopausal Related Symptoms Generic Brand name Available generic Strength (mg) Route of administration Indications Dosing Source of active ingredients FDA approved Bioidentical Etinyl estradiol Estinyl No 0.02 0.05 0.5 Oral Moderate-­‐severe VmS Continuous Syntehsized from soy and yams Yes No To reduce risk of endometrial hyperplasia in postmenopausal women who are taking estrogen and have an intact uterus Secondary amenorrhea Abnormal uterine bleeding due to hormonal imbalance Cyclic continuous Synthesized from soy or yams Yes No Cyclic continuous Synthesized from soy or yams Yes No Cyclic continuous Synthesized from soy or yams Yes No Cyclic continuous Synthesized from Mexican yams Yes Yes Branded hormone therapeutics: Progestogens Medroxypro-­‐
gesterone acetate Amen Yes 10 Oral Medroxypro-­‐
gesteron acetate Cycrin Yes 2.5 5 10 Oral Medroxypro-­‐
gesteron acetate Provera Yes 2.5 5 10 oral Micronized progesterone Crinone No 4% w/w (45); 8% w/w (90) Vaginal gel Micronized progesterone Prometrium No 100 200 Oral Cyclic continuous Synthesized from Mexican yams Yes Yes Norethindrone acetate Aygestin No 5 Oral Cyclic Synthesized from soy Yes No CE MPA 0.625 0.625 0 5 Oral Cyclic Pregnant mares’ urine Yes No CE MPA 0.3 1.5 0.45 1.5 0.625 2.5 0.625 2 Oral Branded hormone therapeutics: Estrogens + progestogens Conjugated estrogens PremPhase No Medroxypro-­‐
gesterone acetate Congugated estrogens Medroxypro-­‐
gesteron acetate PremPro No Moderate-­‐severe VmS; moderate-­‐
severe vulval and vaginal atrophy; Prev. Ost. Synthesized from soy and yams Continuous combined Pregnant mares’ urine Synthesized from soy and yams No Yes No Table 1. Common Hormone Therapies for Relief of Menopausal Related Symptoms Generic Brand name Available generic Strength (mg) Route of administration Indications Dosing Source of active ingredients FDA approved Bioidentical Esterified estrogens EstraTest No 1.25 2.5 Oral Moderate-­‐severe VmS in patients not responsive to estrogen alone Continuous combined Synthesized from soy and yams Yes No 0.625 1.25 Oral 1 0.5 Oral E2 NETA 0.62 2.7 0.51 4.8 Transdermal patch Methyltestosterone Esterified estrogens EstraTest HS No Methyltestosterone Estradiol Activella No Norethindrone acetate Estradiol Combi-­‐
patch No Synthesized from soy and yams OrthoPref
est No Norgestimate Ethinyl estradiol Tablet 1 Tablet 2 1 
1 Continuous combined Moderate-­‐severe VmS; moderate-­‐severe vulval and vaginal atrophy; Prev. Ost. Continuous combined No Norethindrone acetate Yes Synthesized from soy and yams Synthesized from soy and yams Oral Moderate-­‐severe VmS; moderate-­‐severe vulval and vaginal atrophy 0.05/0.25/
E2/ Continuous combined 0.05/0.14 or Synthesized from NETA per day Continuous cycling is achieved using Vivelle Synthesized from soy Moderate-­‐severe VmS; moderate-­‐severe vulval and vaginal atrophy; Prev. Ost. Pulsed Tablet 1 (days 1-­‐5) Tablet 2 (days 4-­‐6) and repeat Synthesized from soy EE NETA 0.0025 0.5 0.0025 0.5 0.005 1 0.005 1 Oral Moderate-­‐severe VmS; Prev. Ost. Continuous Yes Yes No Yes Mexican yams Synthesized from soy No No Yes No Yes Synthesized from soy 0 0.09 Femhrt Synthesized from soy and yams Synthesized from soy Norethindrone acetate Estradiol Moderate-­‐severe VmS in patients not responsive to estrogen alone No Yes No Yes Synthesized from soy No No Branded hormone therapeutics: Testosterone Testosterone Androderm No 2.5 5 Transdermal patch NAMS: low libido Continuous Synthesized from soy No Yes Testosterone Androgel No 25 50 Transdermal patch NAMS: low libido Continuous Synthesized from soy No Yes Testosterone Testoderm No 4 5 Transdermal patch NAMS: low libido 5 mg/day Continuous Synthetic? No Yes Table 1. Common Hormone Therapies for Relief of Menopausal Related Symptoms Generic Brand name Available generic Strength (mg) Route of administration Indications Dosing Source of active ingredients FDA approved Bioidentical Testosterone cypionate Depo-­‐test-­‐
osterone Yes 100 mg/mL IM Low libido Twice/month Synthetic Yes Yes (prodrug is metabolized into BH) Testosterone enanthate Delatestryl Yes 100mg/mL 200mg/mL IM Low libido Twice/month Synthetic? Yes Yes (prodrug is metabolized into BH) Compounded hormone therapeutics: Estrogens, progesterone, testosterone Estradiol Estriol Estrone (triest) N/A, Compounded Customized (usually 1.25, 2.5, 5) Customized for each patient, criteria vary: saliva, sera levels, or symptoms (usually 1.25, 2.5, 5) Oral, trans-­‐dermal; sublingual, vaginal Claims vary Assumed: moderate-­‐
severe VmS/
moderate-­‐
severe vulvar and vaginal atrophy Continuous twice daily (Claimed to be less commonly used due to Estrone content Synthesized from soy No Yes Estradiol Estriol (biest) N/A, Compounded Customized for each patient, criteria vary: saliva, sera levels, or symptoms (usually 1.25, 2.5, 5) Oral, trans-­‐dermal; sublingual, vaginal Claims vary Assumed: moderate-­‐
severe VmS/
moderate-­‐
severe vulvar and vaginal atrophy Continuous twice daily, commonly 1.25 mg BID Synthesized from soy No Yes Estriol N/A, compounded Customized for each patient, criteria vary: saliva, sera levels, or symptoms Oral, trans-­‐dermal; sublingual, vaginal Claims vary Assumed: moderate-­‐
severe VmS/
moderate-­‐
severe vulvar and vaginal atrophy Continuous Synthesized from soy No Yes Table 1. Common Hormone Therapies for Relief of Menopausal Related Symptoms
Generic Brand name Progesterone N/A, compounded Available generic Strength (mg) Route of administrati
on Indications Dosing Source of active ingredients FDA approved Bioidentical Customized for each patient, criteria vary: saliva, sera levels, or symptoms Oral, trans-­‐
dermal; sublingual, vaginal, injectable Claims vary FDA: protection from estrogen-­‐
associated endometrial hyperplasia and adenocarcino
mas Continuous cyclic Synthesized from soy or yams Yes Yes Claims vary NAMS: decreased libido; NAMS does not recommend the use of compounded product Continuous Synthesized from soy Oral and IM only Yes Monthly Twice/month Synthetic? Yes Yes (prodrug is metabolized into BH) Testosterone N/A, compounded Customized for each patient, criteria vary: saliva, sera levels, or symptoms Oral, trans-­‐
dermal; sublingual, vaginal, injectable Testosterone propionate N/A, compounded Customized for each patient, criteria vary: saliva, sera levels, or symptoms IM Vasomotor: Case Study
A fifty three year old woman presents for an annual
check-up. She is two years post-menopausal, is
currently taking Paroxetine for well controlled
depression. She has no other chronic medical
problems and was referred by her primary to talk
about potential treatments for hot flashes. Vital
signs include b/p 112/62 and bmi of 25. She has
had yearly mammograms that are normal.
Vaginal: vulvar & vaginal atrophy (dryness, dysparenunia, and
atrophic vaginitis)
Treatments
•  OTC Water/Silicone based
moisturizers & lubricants
•  Topical Hormones
•  Ospemifene (Selective Estrogen
Receptor Modulator)
•  Use moisturizers daily,
use lubricants with sex
•  Ring may be absorbed
less systemically
•  Treats moderate to
severe dyspareunia,
associated with ↑ hot
flashes, ↑ stroke &
thromboembolic events
Vaginal Case Study
Sixty-One year old woman with Rheumatoid arthritis.
History of frequent clinic visits for dysuria and negative
lab studies to support urinary infections. Had not been
having sex for years. Vaginal exam with pale, dry
introitus, rugae not present.
BMI 42
Bone
•  Estrogen
•  Decreased risk of hip
fracture
•  ? Consider use for
prevention
•  Selective Estrogen Receptor Modulators:
Raloxifene and Bazedoxifene (use with CE in women
with a uterus)
•  Calcium
•  Vitamin D
•  Increasing calcium intake,
through calcium
supplements or dietary
sources, should not be
recommended for fracture
prevention
Other
•  Cardiovascular
•  Cognitive
Case study:
63 year old woman requests a refill of her “bio identical
hormone” prescription. She takes this for her
duodenitis, tendon pain, urinary incontinence, skin, hot
flashes (she has tried EVERYTHING else and it is the
ONLY thing that works), memory, leg swelling, varicose
veins, bloating (had terrible IBS prior), osteopenia, and
vaginal dryness.
Does not get mammograms due to concern for “radiation
exposure”.
References:
Alternative Medicine for Menopause. Endocrine Society. 2012 Bio-­‐Identicals: Sorting Myths from Facts. U.S. Food and Drug Administration. 2004 Bioidentical Hormone Therapy: A Review of the Evidence. Journal of Women’s Health. 2007; 16(5)600-­‐631 Calcium intake and risk of fracture: systematic review. The BMJ 2015; 351 Charting a Course Through Changing Tides: An Evidence-­‐Based Examination of Hormone Therapy in Women’s Health. Compounded bioidentical hormone therapy: time for a reality check? Andrew Kaunitz, Menopause, September 2015 Global Consensus State Hormone Therapy. Endocrine Society. 2013 The Kronos Early Estrogen Prevention Study. Women’s Health. 20139 (1):9-­‐11 http://www.menopause.org/publications/clinical -­‐care-­‐recommendations NIH Asks Participants in Women’s Health Initiative Estrogen-­‐Alone Study to Stop Pills, Begin Follow-­‐up Phase. Barbara Alving. March 2, 2004. Perspectives in Prevention From the American College of Preventive Medicine The Women’s Health Initiative: The Role of Hormonal Therapy in Disease Prevention, Robert Wallace, 3(1), 2005