Download Menopause Drugs Menopause: permanent cessation of menses

Menopause Drugs 1
Menopause: permanent cessation of menses following the loss of ovarian follicular activity
Defined as 12 consecutive months of amenorrhea
Caused by: aging (natural menopause), surgery (hysterectomy), medications, pelvic irradiation
Signs and Symptoms of Menopause:
Symptoms: vasomotor (hot flash/night sweat), sleep disturbances, mood changes, sexual dysfunction,
memory difficulties, vaginal dryness, dyspareunia, arthralgia
Signs: menstrual cycle irregularity (perimenopause), urogenital atrophy (menopause)
Labs: FSH > 10-20 (perimenopause) or > 40 (menopause)
Metabolic Changes: wt redistribution ( central abdominal fat); lipid profile; vascular function; bone metabolism
Considerations for HT: severity of symptoms, osteoporosis risk, CV dz, breast CA, thromboembolism
Drug
Class
Drug
Layer clothing
Nonpharmacologic
Lower room temp
Decrease hot/spicy
food, caffeine, hot
beverages
Exercise
Yoga
Acupuncture
MOA
Pharmacokinetics/
dynamics
Indications
AE/DI/CI
Other
Menopause Drugs 2
Drug
Class
Drug
MOA
Pharmacokin/dynam
Indications
AE/DI/CI
Other
Estrogen
Inhibits ovulation
by suppressing
FSH and LH
Oral
Transdermal
Topical
Intravaginal
IM
Most effective option for
alleviating vasomotor
symptoms, vaginal
symptoms, and
improving sleep quality
FDA -approved
AE:
Nausea
HA
Breast tenderness
Bleeding
 triglycerides
Coagulation parameters
Minimize Risks
via:
(prescribed +/progestogen)
Hormone Therapy
Alters secretions
and cellularity of
the endometrium
Conjugated
equine estrogens
17 β- estradiol
Oral forms are
metabolized by
Induces luteolysis GI mucosa and
the liver with
Provides cycle
high first pass
control
Non-oral forms
bypass the GI
and have less
effect on lipids
and coag
Relief of:
Vasomotor sympt.
Atrophic vaginitis
Prevention of
postmenopausal
osteoporosis
Low systemic
concentrations
w/ intravaginal
preparations
Benefits:
 bone resorption
(prevent osteoclast
maturation and induce
apoptosis)
 LDL  HDL
 risk of colon CA
CI to HT:
Active liver dz,
Thromboembolic dz,
Breast CA,
Estrogen sensitive
malignancy,
Known hypersensitivity,
Prophyria cutanea tarda,
Undiagnosed genital
bleeding,
Untreated endometrial
hyperplasia,
Untreated HTN
Risks:
 risk of gallstones
 risk of VTE
 risk of breast CA
 triglycerides
(CV dz increased in 1st
two years of HT)
Limiting
duration of use
Using the
lowest required
dose
Attempting
D/C annually
Smoking
cessation
Menopause Drugs 3
Drug
Class
Drug
MOA
Pharmacokin/dynam
Indications
AE/DI/CI
Other
Progestogen
Inhibits ovulation
by suppressing
the LH mid-cycle
surge
Oral
Transdermal
Most effective option for
alleviating vasomotor
symptoms, vaginal
symptoms, and
improving sleep quality
AE:
Irritability
Depression
HA
Minimize Risks
via:
(prescribed with
estrogen therapy)
Hormone Therapy
Inhibits
implantation by
suppressing the
endometrium
Medroxyprogest- Thickens cervical
mucus
erone acetate
(MDPA) (Provera)
Slows tubal
motility and
Micronized
delays sperm
progesterone
(Prometrium)
transport
Norethindrone
acetate
Increases basal
insulin levels
and insulin
response to
glucose
Stimulates
lipoprotein
lipase activity
fat deposition
Metabolized in
the liver to
inactive
products
Excreted in the
urine
Indicated for women
who have NOT
undergone a
hysterectomy
Other Indications:
Contraception
Dysfunctional uterine
bleeding
Note: NOT used in cases
with hysterectomy since
progesterone is used to
balance uterine
hyperplasia and decrease
cancer risk with estrogen
use
CI to HT:
Active liver dz,
Thromboembolic dz,
Breast CA,
Estrogen sensitive
malignancy,
Known hypersensitivity,
Prophyria cutanea tarda,
Undiagnosed genital
bleeding,
Untreated endometrial
hyperplasia,
Untreated HTN
Limiting
duration of use
Using the
lowest required
dose
Attempting
D/C annually
Smoking
cessation
Menopause Drugs 4
Selective Estrogen Receptor Modulators
(SERMs)
Selective Estrogen Receptor Modulators
(SERMs)
Drug
Class
Drug
MOA
Tamoxifen
Chemically
distinct from
estradiol
(nonsteroidal
compounds)
Toremifene
Pharmacokin/dynam
Indications
AE/DI/CI
Breast CA
Acts as an
agonist in bone
and in
coagulation
Acts as an
antagonist in the
breast and
vasomotor center
Raloxifene
(Evista)
Chemically
distinct from
estradiol
(nonsteroidal
compounds)
Acts as an
agonist in bone
and in
coagulation
Acts as an
antagonist in the
breast, uterus,
and vasomotor
centers
Metabolized
extensively in
the liver
Prevention
And Treatment of
Osteoporosis
Excreted in the
feces
Reduction of invasive
breast CA in high risk
women
Highly protein
bound
NOT useful for
menopausal symptoms
(see AEs)
AE:
Does NOT alleviate hot
flashes
May EXACERBATE
hot flashes
Leg cramps
Increased risk of
thromboembolism
Other
Menopause Drugs 5
Selective Estrogen Receptor Modulators (SERMs)
Drug
Class
Drug
MOA
Pharmacokin/dynam
Indications
AE/DI/CI
Ospemifene
(Osphena)
Chemically
distinct from
estradiol
(nonsteroidal
compounds)
Metabolized
via:
CYP3A4
CYP2C9
CYP2C19
Moderate  severe
dyspareunia
Vulvar and vaginal
atrophy
AE:
 risk of DVT
 risk of PE
Hot flushes
Vaginal discharge
Muscle spasm
Genital discharge
Hyperhidrosis
(excessive sweating)
Acts as an
agonist in bone,
endometrium,
and in
coagulation
Acts as an
antagonist in the
breast and
vasomotor center
DI:
Fluconazole
(inhibits metabolism)
Ketoconazole
(inhibits metabolism)
Rifampin
(induces metabolism)
Use with progestin if
uterus is present due to
agonistic actions on
endometrium
Other
Menopause Drugs 6
Selective Estrogen Receptor Modulators
(SERMs)
Drug
Class
Drug
MOA
Bazedoxifene
Chemically
distinct from
estradiol
(nonsteroidal
compounds)
Acts as an
agonist in bone
and in
coagulation
Combination
Estrogen +
SERM
Conjugated
estrogens
+
Bazedoxifene
(DuaVee)
Acts as an
antagonist in the
breast, uterus,
and vasomotor
centers
Combination of
estrogen and
estrogen agonist/
antagonist
(SERM)
Pharmacokin/dynam
Indications
Menopausal vasomotor
symptoms
Prevention of
postmenopausal
osteoporosis (in
combination with
estrogen)
Used to decreased
endometrial hyperplasia
with estrogen therapy
 BMD in spine and hip
(bone mineral density)
But NO fx data available
Treatment of menopausal
vasomotor symptoms
Prevention of
postmenopausal
osteoporosis
AE/DI/CI
Other
Menopause Drugs 7
Drug
Class
Drug
MOA
Bisphosphonates
Inhibits bone
resorption (depth)
to produce a
positive bone
balance
via shortening the
life span of
osteoclasts
Bisphosphonates
Alendronate
(Fosamaz)
Risedronate
(Actonel)
Pharmacokin/dynam
Indications
AE/DI/CI
Prevention
And Treatment
of osteoporosis
AE:
GI disturbances
Difficulty swallowing
Heartburn
Esophagitis/ulceration
Abdominal pain
Osteonecrosis of jaw
Prevention of
osteoporosis
AE:
Constipation
Intestinal bloating
Excess gas
Ibandronate
(Boniva)
Zoledronate
(Reclast)
Vitamins
Minerals
Calcium
Vitamins Minerals
Vitamin D
Prevention of
osteoporosis
DI:
Certain antibiotics
AE:
Well-tolerated
Other
Menopause Drugs 8
Drug
MOA
Calcitonin
(Miacalcin)
(Fortical)
Teriparatide
(Forteo)
Synthetic
Vitamins
Minerals
Drug
Class
Indications
AE/DI/CI
Inhibits bone
resorption via
reducing the life
span of
osteoclasts
Treatment of osteoporosis
AE:
Nasal irritation, rhinitis
Epistaxis
HA
Arthralgia
Synthetic human
parathyroid
hormone
Treatment of osteoporosis
AE:
Nausea
Muscle cramps
Hypercalcemia
Transient hypotension
Treatment of osteoporosis
AE:
Back and MSK pain
Serious infection
Dermatologic rxn
Hypercholesterolemia
Activates
osteoblasts to
stimulate new
bone formation
Denosumab
(Prolia)
Monoclonal Antibody
Pharmacokin/dynam
Human IgG2
monoclonal
antibody inhibits
RANK ligand
Inhibits
osteoclast
formation,
function, and
survival
Decreases bone
resorption and
increases bone
mass and strength
Other
Menopause Drugs 9
Androgens
Drug
Class
Drug
MOA
Pharmacokin/dynam
Indications
AE/DI/CI
Testosterone
Oral (daily)
Methyltestosterone in
combination with
esterified
estrogens
Transdermal
(q6mo)
Lack of documented
clinical and biochemical
findings of androgen
deficiency in women
AE:
Increased facial/body hair
(virilization)
Increased acne
Reduced HDL
Fluid retention
Subcutaneous
(q3-4days)
However, still being
used for:
Diminished well-being
Unexplanied fatigue
Decreased libido
Decreased sexual
receptivity and pleasure
CI:
Androgen-dependent CA
Moderate/severe acne
Hirsuitism
Androgenic alopecia
Long-term safety
unknown
Other
Menopause Drugs 10
Drug
Class
Drug
MOA
Pharmacokin/dynam
Hot flushes
Tibolone
Venlafaxine
Desvenlafaxine
Paroxetine:
CYP2D6
inhibitor
Paroxetine
Megesterol
acetate
Other Estrogen Alternatives
Clonidine
Gabapentin
Citalopram
Sertraline
Fluoxetine
Tamoxifen
Indications
Fluox:
CYP2D6
inhibitor
Tamox: estrogen
receptor blockade
Tamoxifen:
metabolized by
CYP2D6 to
endoxifen
AE/DI/CI
Other
Menopause Drugs 11
Other
Alternatives
Drug
Class
Drug
MOA
Black cohosh
Cimicifuga
racemosa
Indications
AE/DI/CI
Estrogenic
properties vs
serotonergic
effects
Possibly effective for
menopausal symptoms
AE:
Hepatotoxicity
Plants
compounds with
estrogen-like
activity
Hot flushes
Menopausal symptoms
Isoflavones
Lignans
Coumestans
Soy beans
Cereals
Flaxseed
(lignans)
Alfalfa Sprouts
(coumestans)
Other
Alt
St. John's wort
Supplements
Water-soluble
lubricants
Other Alternatives
Other
Remifemin
Phytoestrogens
Other Alternatives
Pharmacokin/dynam
Lubricant:
temporary, short
duration
AE:
Compromises condom
integrity
Decreased sperm motility
Moisturizer:
long-term relief
bioadhesive
polycarbophilbased polymer
attaches to mucin
and epithelial
cells
AE:
Lowers vaginal pH
Spermicidal activity
in vitro
And
Moisturizers
Replens