Objectives
1. Recommend appropriate treatment options for
patients with menopausal symptoms, osteoporosis,
infertility and sexual dysfunction.
1
Agenda
Menopause
Osteoporosis
Contraception
Pregnancy and Lactation
Infertility
Sexually Transmitted Infections
Sexual Dysfunction in Men
Endometriosis*
Polycystic Ovary Syndrome*
Patient Case 1
N.I. is a 51-year-old woman complaining of hot
flashes and vaginal irritation. Has tried exercise, diet,
and antidepressants and is unsuccessful. Otherwise
healthy with no history of cancer and no surgeries.
States hot flashes are interfering with her daily
activities and wants to try hormone therapy.
2
Hormone Regimens
Unopposed Estrogen
PEPI Trial, JAMA. 1995 Jan 8;273(3):199-208.
Estrogen plus cyclic progestogen
(progestin)
Estrogen plus daily progestogen
Heart and Estrogen/Progestin Replacement
Study, JAMA. 1998 Aug 19;280(7):605-13)
Womens Health Initiative WHI JAMA. 2002 Jul
17;288(3):321-33
Updates
Ovarian cancer, JAMA. 2009 Jul
15;302(3):298-305
Noted about 1 extra case per 8300
women taking HT, controversial, rare
Lung cancer , Lancet. 2009 Oct
10;374(9697):1243-51.
Incidence per year similar between groups
More deaths in HT group related to non-small-
cell lung cancer (62 vs 31 deaths; 009% vs
005%; HR 187, 122-288, p=0004)
Not designed to evaluate lung cancer, smokers,
past smokers, average age 60, more studies
needed
3
References
Estrogen and progestogen use in
postmenopausal women: 2010 position
statement of The North American
Menopause Society
Menopause Vol. 17; No. 2 pp 242-55.
Also found at
http://www.menopause.org/PSht10.pdf
4
Alternatives for Vasomotor
Symptoms (pg 40)
Fluoxetine (Prozac) 20 mg PO daily
Paroxetine (Paxil) 20 mg PO daily
Venlafaxine (Effexor) 75 mg PO daily
Decreased frequency and severity of
hot flashes vs. placebo
Others
Loprinzi C et al. The Lancet 2000;356:2059-2063.
Loprinzi C et al. Journ Clin Oncol 2002;20(6):1578-1583.
Stearns C et al. Annal Oncol 2000;11:17-22.
Patient Case 1
Response Cards
N.I. is a 51-year-old woman complaining of hot
flashes and vaginal irritation. She has tried exercise,
diet, and antidepressants to help relieve her hot
flashes but has been unsuccessful. She is otherwise
healthy with no history of cancer and no surgeries.
She states her hot flashes are interfering with her
daily activities and wants to try hormone therapy.
A Alora patch 0
A. 0.025
025 mg; change patch
twice weekly
B. Climara 0.025 mg; change patch once
weekly
C. Prempro 0.3 mg/1.5 mg; take 1 tablet PO
daily
D. Premarin 0.625 mg; take 1 tablet PO
daily
Page 37
5
Patient Case 1
N.I. is a 51-year-old woman complaining
of hot flashes and vaginal irritation. She
has tried exercise, diet, and
antidepressants to help relieve her hot
flashes but has been unsuccessful. She
is otherwise healthy with no history of
cancer and no surgeries. She states her
hot flashes are interfering with her daily
activities and wants to try hormone
therapy.
Page 37
A Alora patch 0
A. 0.025
025 mg; change patch
twice weekly
B. Climara 0.025 mg; change patch once
weekly
C. Prempro 0.3 mg/1.5 mg; take 1 tablet PO
daily
D. Premarin 0.625 mg; take 1 tablet PO
daily
Page 37
6
Osteoporosis Definitions
World Health Organization Definitions
Risk Factors
Female Estrogen deficiency
White race Low body mass index (BMI) or
low weight
Poor nutrition, long-term low-
Family history of osteoporosis
calorie intake Low calcium and vitamin D
Early menopause (before age intake
45) or prolonged Sedentary lifestyle, decreased
premenopausal amenorrhea y
mobility
Drugs: Cigarette smoking
Alcoholism
Glucocorticoids
Dementia
Heparin Impaired eyesight despite
Anticonvulsants adequate correction
Excessive levothyroxine Previous fractures
History of falls
GnRH agonists
Lithium
Cancer drugs
Page 41
7
Screening Recommendations
(Women) Page 41
BMD Measurements:
All women >65 years
Postmenopausal women with medical
causes of bone loss (hyperparathyroidism,
steroid
t id use))
Postmenopausal women age 50 with risk
factors: fracture after menopause, wt <127
lbs or BMI <21 kg/m2 , smoker, parent w/
hip fracture, rheumatoid arthritis, alcohol >
2 units/day
Postmenopausal women with fragility
fracture
Screening Recommendations
(Men)
BMD Measurements:
Older than 70 years old
Ages 50-70
50 70 with risk factors or previous
fractures
23 (45)
References
NAMS Position Paper Published 2010
Menopause Vol. 17; No.1 pp 24-25.
Also found at
http://www.menopause.org/PSosteo10.pdf
AACE Medical Guidelines for Diagnosis and
Treatment of Postmenopausal
Osteoporosis
Endocr Pract. 2010;16(Suppl 3)
Found at www.aace.org
8
Patient Case 2, Question 3
Answer
3. C.A. is a 71-year-old white woman who rarely drinks
alcohol, does not smoke, and exercises for 30
minutes 3 times/week. She takes calcium 500 mg
/vitamin D 400 IU 3 times/day. She is 53 and weighs
140 lb. Her BMD T-score is 1.8 at the hipp and
2.6 at the spine. Which one of the following
statements is the correct diagnosis for C.A.?
Lifestyle Modifications
Recommendations
Advise patient to avoid smoking and to
consume only moderate amounts of alcohol.
Encourage regular weight-bearing and
muscle-strengthening exercise.
Encourage adequate intake of calcium (at
least 1200 mg/day) and vitamin D (600800
IU/day). For older than 70 years 800 IU/day
Assess fall risks
Page 43, 45
9
Start Drug Therapy
Based on NOF, AACE, and NAMS
recommendations:
Hip or spine fracture
T-score <-2.5 or below at hip, spine, or
f
femoral l neck
k
T-score between -1.0 and -2.5 with a 10-
year probability of a hip fracture 3% OR a
10-year probability of a major
osteoporosis-related fracture 20% based
on the FRAX tool (US-adapted WHO
algorithm)
Pages 41, 42
Current Treatments
Bisphosphonates (1st line)
SERMs
Teriparatide (rPTH 134)
Estrogen Therapy
Calcitonin
Denosumab
Others
Pages 42-45
Bisphosphonates
Inhibit osteoclasts, reduce bone resorption
Adverse effects: Oral agents most common is
esophageal/gastric irritation
Must be taken on an empty stomach and remain
upright for at least 30 min. (60 min for ibandronate)
Reduce risk of vertebral fractures by 40-70%
Reduce risk of non-vertebral fractures (hip) by 20-
35%
Only use in patients with GFR of > 30mls /min
Osteonecrosis of jaw,
spontaneous fractures (?) Pages 42 - 43
10
Bisphosphonates
Alendronate (Fosamax) PO daily or weekly
Risedronate (Actonel) PO daily, weekly,
monthly
**Risedronate (Atelvia) PO weekly (delayed
release, take 30 min. after breakfast, avoid
PPI use))
Ibandronate (Boniva) PO daily, monthly or IV
Q 3 months
Zolendronic acid (Reclast) IV yearly or Q 2
years for prevention
Etidronate (approved in Canada for
osteoporosis) Pages 42 - 43
Current Treatments
SERMs (Selective Estrogen Receptor
Modulators)
Raloxifene 60 mg PO daily, only SERM approved
for prevention and treatment of osteoporosis
risk of vertebral fracture by 55% (MORE data)
in women with T-score < -2.5 and by 30% in
women with low T-scores
No effect observed for non-vertebral (hip) fracture
Adverse Effects: VTE events, may cause hot
flashes or leg cramps
Pages 43 - 44
11
Teriparatide (rPTH 134)
Subcutaneous inj 20 mcg/day for up to 18-24
months, bone formation
Approved for treatment for those at high risk of
fracture
Rare risk of bone tumors (seen in rats)
Estrogen Therapy
Approved for prevention
Calcitonin
Approved for treatment, inhibits resorption, usually
alternative if other agents cannot be used
Nasal spray 200 IU daily, best for vertebral
fractures- reported 33%
May help with bone pain
Page 44
12
Patient Case 4, Question 5
5. S.E. is a 28-year-old woman who would like to get
pregnant soon. Her medical history includes
hypertension and seasonal allergies. Her drugs
include lisinopril, nasal saline spray, and folic acid.
Whi h one off th
Which the ffollowing
ll i iis bbestt tto ttreatt h
her
hypertension while pregnant or trying to conceive?
A. Continue on lisinopril
B. Discontinue lisinopril and all other medications
C. Discontinue lisinopril and start methyldopa
D. Continue lisinopril and add metoprolol
Page 48
FDA Classifications
Simpler Form:
A: Controlled studies show no risk
B: No evidence of risk in humans
C: Risk cannot be ruled out
D: Positive evidence of risk
X: Contraindicated in pregnancy
Page 46
13
Known Teratogens
Isotretinoin ACE inhibitors
Methotrexate DES
Alcohol Streptomycin
Mercuryy Warfarin
Lead
Thalidomide
Carbamazepine
Androgens
Lithium
Cocaine Tetracycline
Phenytoin Vitamin A
Valproate Statins
Topiramate
See page 47 for more complete lists
Conditions in Pregnancy
GI
Nausea and vomiting, constipation,
heartburn
Hypertension
yp
Anticoagulation
Diabetes ADA Guidelines
Depression APA and ACOG
guidelines
Page 49 - 51
Page 48-49 Hale, Thomas. Medications and Mothers Milk. 11th Edition 2004
#43
14
Patient Case 4, Question 5
5. S.E. is a 28-year-old woman who would like to get
pregnant soon. Her medical history includes
hypertension and allergies. Her drugs include
lisinopril, nasal saline spray, and folic acid. Which
one of the following is best to treat her
hypertension
yp while ppregnant
g or trying
y g to conceive?
A. Continue on lisinopril
B. Discontinue lisinopril and all other medications
C. Discontinue lisinopril and start methyldopa
D. Continue lisinopril and add metoprolol
Page 48
Page 58
Ortho Cept
Ortho-Cept Intermediate High Low
(Desogestrel 0.15mg
/EE 30 mcg)
Lessina Low Low Low
(Levonorgestrel
0.1mg/EE 20mcg)
Loestrin 21 Low Low High
(Norethindrone acetate
1.5 mg/ 30 mcg)
15
Contraceptive Methods
Combined Hormonal Contraceptives
Oral tablet, chewable tablet
Patch
Vaginal
g Ring g
Progestin Only
Oral tablet
Injection
Implant
Intrauterine system
Non-hormonal
46
Starting Methods
(Combined Hormonal Contraception)
Sunday Start-
Start- 1st Sunday after
menses begins
First
Fi t DDay St
Startt- Start
Start- St t method
th d first
fi t
day of menses
Quick Start-
Start- Start method at clinic
regardless of time in cycle
Page 59-60
16
Page 57
Side Effects of Combined
Contraceptives
ESTROGENIC PROGESTATIONAL &
Nausea, vomiting ANDROGENIC**
Bloating, edema Headaches
Irritability Increased
I d appetite
tit
Cyclic weight gain Increased weight
Cyclic headache gain
Hypertension Depression, fatigue
Breast fullness, Changes in libido
tenderness Hair loss,
hirsutism**
Acne, oily skin**
Page 57
Page 57
17
Management of Side Effects:
Breakthrough Bleeding and Spotting
When switch is indicated:
Change progestin:
If bleeding begins after 14 days (of active med)
Progestin should have higher progestational
and/or androgenic activity
Increase both estrogen and progestin:
If bleeding occurs midcycle
Page 57
Page 58
Ortho Cept
Ortho-Cept Intermediate High Low
(Desogestrel 0.15mg
/EE 30 mcg)
Lessina Low Low Low
(Levonorgestrel
0.1mg/EE 20mcg)
Loestrin 21 Low Low High
(Norethindrone acetate
1.5 mg/ 30 mcg)
18
Patient Case 5, Question 6
6. Y.G. is a 33-year-old woman who was initiated on
Mircette 4 months ago for contraception. She has
break-through bleeding at the start of her active
pills that lasts a few days before resolving. The
physician
p y wants to change
g the OC. Which one of
the following OCs on her formulary should the
physician prescribe?
Page 58
A. Ortho-Evra
B. YAZ
C. Micronor
D. Mirena
Page 67
Combined Contraceptives:
Drug Interactions
Hepatic enzyme inducers
Agents most likely to cause breakdown of estrogen or
progestin: phenobarbital, phenytoin, topiramate,
p ,p
carbamazepine, primidone
Sodium valproate, ethosuximide, lamotrigine* and
vigabatrin do not effect contraceptive hormone levels
Management
Use another method
Use different anticonvulsant
Increase dose of contraceptive
Page 58,59
19
Combined Contraceptives:
Drug Interactions
Recommendations by Council of Scientific Affairs to AMA
Rifampin - significant risk of failure; counsel about the use of
additional nonhormonal contraceptive methods during the
course of rifampin therapy
Other antibiotics - small risk of interactions; not possible to
identify women who may be at risk of OC failure. Recent
WHO/CDC eligibility criteria classified as category 1.
Counsel about the additional use of nonhormonal
contraception or alternate methods for:
Those not comfortable with small risk of interaction
Those with previous failures or who develop
breakthrough bleeding during use of antibiotics
WHO Medical Eligibility for Contraception 2009
Obstet Gynecol 2001;98:53-60
Controversies
Transdermal Patch
Increased exposure to estrogen, 60% more
estrogen than in women taking 35 mcg of EE
? Increased risk of VTE, cardiovascular and
cerebrovascular events
Less effective in women > 198 lbs. , (90kg)
Extended Use of Hormonal Contraception
3 month formulations
1 year formulations
Breakthrough bleeding common
Page 61
20
New Products
Natazia (estradiol valerate/dienogest)
Quadriphasic
Safyral (ethinyl estradiol 30 mcg /drospirenone 3 mg)
Beyaz }
Contains 0 0.451
451 mg levomefolate calcium (folic acid)
(ethinyl estradiol 20 mcg /drospirenone 3 mg)
Contraceptive Methods
Combined Hormonal Contraceptives
Oral tablet
Patch
g
Vaginal Ringg
} Pages 59 - 63 for use,
missed doses
Progestin Only
Oral tablet
Injection
Implant
Intrauterine system
Non-hormonal
21
Depot Medroxyprogesterone
Acetate (DMPA) Injection
Injection administered Q 11-13 weeks
Side effects
Weight gain
Mood issues, other progestin related
effects
Long return to fertility
Possible decrease in BMD, especially in
younger women with use > 5 years
Page 64, 65
Levonorgestrel
IUS
Page 66,67
Page 67
Implantable Rod
Implanon (etonogestrel)
Releases 25-45 mcg/day over 3 years
Very effective, suppresses ovulation in 97% of cycles
g and effectiveness
Concern with weight
Limited information in women > 130% of their
body weight
22
Patient Case 6, Question 7
Response Cards
6. L.M. is a 37-year-old woman, states she is going to
get married soon and would like to begin birth control
pills for now but would like to have children in a year
or so. Past medical history includes hypertension x 2
years, GERD, admits to 2 glasses of wine/week and
smokes pack per day. Her medications include
HCTZ 25 mg PO daily, Lotrel 5/20
( l di i /b
(amlodipine/benazepril)il) PO d
daily,
il PPrilosec
il 20 mg
(omeprazole) PO daily, and occasional ibuprofen.
She is 57, Weight: 210 lbs. (95kg) Which one of the
following contraceptive products should the physician
prescribe?
A. Ortho-Evra
B. YAZ
C. Micronor
D. Mirena Page 67
EC Methods
Yuzpe Regimen estrogen + progestin
Levonorgestrel progestin only
Plan B (Next Choice) (0.75 mg, 2 tablets in package), tablets
may be taken 12 hours apart or together at one time.
Plan B One Step (1.5 mg, 1 tablet taken as soon as possible
after unprotected intercourse).
OTC for 17 years and older
Ulipristal acetate Selective Progesterone
Receptor Modulator (SPRM)
Ella 30 mg, 1 tablet taken as soon as possible after
unprotected intercourse, labeled for 120 hours, prescription-
only
Copper IUD (up to 5 days after ovulation)
Mifepristone (off label use, up to 5 days after
sexual intercourse)
Pages 68,69
Indications
Unprotected intercourse in the past 72 hours
(120 hours)
Contraceptive failure
Condom breaks
Missed oral contraceptive pills
Expulsion of IUD or vaginal ring
Patch fell off for long period of time
Displacement of barrier method (diaphragm)
Sexual assault
Exposure to teratogen
Page 68
ACOG Practice Bulletin, Int J of Gynecol Obstet, 2002;78:191-198
23
EC Mechanism of Action
Not clear: depends on time of administration, best
prior to ovulation time
1. Prevents or delays
ovulation
2. Traps sperm in
thickened cervical
mucus
3. May interfere with
fertilization
4. May interfere with
implantation
(controversial)
May causes
endometrial changes Does not cause an abortion
Probably acts prior ACOG Practice Bulletin No. 112, May 2010
#71 to implantation
Effectiveness
(use after one act of unprotected intercourse)
If 100 women have unprotected
sex in the 2nd or 3rd week of
their cycle
88 will become
pregnant without
EC
2 will become pregnant
using combined EC (75%
reduction)
1 will become pregnant
using progestin EC (88%
reduction) Trussell J et al. FPP. 1996;28:58
1996;28:58--64,87 and WHO, 1998
A. Ovidrel (hCG)
B. Synarel (GnRH agonist)
C. Pergonal (hMG)
D. Clomid (clomiphene citrate)
24
Infertility
Potential Causes
85% of couples conceive in 1 year, 15% infertile
Fertility Agents
1. Clomiphene citrate 1st line agent
2. Human menopausal gonadotropin
(hMG)
3. Follicle-stimulating hormone (FSH)
4. Human chorionic gonadotropin (hCG)
5. Gonadotropin-releasing hormone
analogs (GnRH)
Page 70 - 71
A. Ovidrel (hCG)
B. Synarel (GnRH agonist)
C. Pergonal (hMG)
D. Clomid (clomiphene citrate)
25
Sexually Transmitted Infections/Diseases
Pages 73-80
26
HSV
HSV
Recurrent HSV infection
If treatment is initiated within 1 day of lesion onset,
patients with recurrent infections may benefit.
Acyclovir (see page 74 for various regimens)
Famciclovir
Valacyclovir
Suppressive therapy
Recommended in patients with six or more episodes
yearly (reassess annually the need for suppressive
therapy)
Acyclovir 400 mg orally 2 times/day
Famciclovir 250 mg orally 2 times/day
Valacyclovir 500 mg/day orally
Valacyclovir 1000 mg/day orally
Page 74
27
Patient Cases Question 11
11. M.A. is a 24-year-old woman severe abdominal
pain, fever, dysuria, and a vaginal discharge. She is
sexually active with multiple partners. PMH
unremarkable except for recurrent genital herpes
(one or two episodes per year). Medications: Ortho
Tri-Cyclen, fluticasone (Flonase) as needed. Temp.
101.2F (38C), HR 92, RR 15, BP 117/75 mm Hg.
M.A. has adnexal tenderness, cervical motion
tenderness, and a vaginal discharge. Which one of
the following is the best empiric therapy?
Complications
Urethritis
Pelvic Inflammatory Disease
Syphilis (secondary,
(secondary latent,
latent tertiary,
tertiary
neuro)
Prostatitis
28
Patient Case 11 - Response Cards
11. M.A. is a 24-year-old woman who presents to the emergency
department with severe abdominal pain, fever, dysuria, and a
vaginal discharge. She is sexually active with multiple partners.
Her medical history is unremarkable except for recurrent genital
herpes (one or two episodes per year). Her medications on
admission include birth control pills (Ortho Tri-Cyclen) and
fluticasone (Flonase) as needed. On physical examination,
M.A.s vital signs include temperature 101.2F (38C), heart rate
92 beats/minute, respiration rate 15 breaths/minute, and BP
117/75 mm Hg. M.A. has adnexal tenderness, cervical motion
tenderness and a vaginal discharge.
tenderness, discharge Which one of the following
is the best empiric therapy?
Page 76
Page 76
Vaginal Infections
Bacterial Vaginosis
Metronidazole or clindamycin
Fishy odor
Women only treated
Trichomoniasis
Metronidazole
Yellow-green vaginal discharge
** All sexual partners should be treated
Vulvovaginal Candidiasis
OTC antifungals
Intense itchiness and beige, milky discharge
Pages 78-79
29
Patient Cases Question 13
13. A 65-year-old man presents to his physician
complaining of symptoms determined to be erectile
dysfunction (ED). He has a history of
hyperlipidemia, GERD, and glucose intolerance.
His current medications include atorvastatin 20 mgg
PO daily, omeprazole 20 mg PO daily, and aspirin
81 mg as tolerated. He states that he heard of
medications to help with his symptoms but does not
want to have to plan out his intimate moments.
What medication might work best for this patient?
A. Tadalafil
B. Vardenafil
C. Yohimbine
D. Bupropion Page 83 89
SD Treatment in Men
Treat organic cause
Non-pharm: vacuum pump devices, venous
constriction rings
Testosterone replacements: inj., dermal
patch, gel
Phosphodiesterase Type 5 inhibitors:
Sildenafil (Viagra) 50 mg PO 1 hr. prior
Tadalafil (Cialis) 10 mg PO 36 hrs. prior
Vardenafil (Levitra) 10 mg PO 1 hr prior
Yohimbine
Alprostadil: inj. or pellets
SSRIs premature ejaculation
Page 81,82
30
Patient Cases Question 13
response cards
13. A 65-year-old man presents to his physician
complaining of symptoms determined to be erectile
dysfunction (ED). He has a history of
hyperlipidemia, GERD, and glucose intolerance.
His current medications include atorvastatin 20 mgg
PO daily, omeprazole 20 mg PO daily, and aspirin
81 mg as tolerated. He states that he heard of
medications to help with his symptoms but does not
want to have to plan out his intimate moments.
What medication might work best for this patient?
A. Tadalafil
B. Vardenafil
C. Yohimbine Page 83
D. Bupropion
A. Tadalafil
B. Vardenafil
C. Yohimbine
D. Bupropion
Page 83
Questions
31