An overview of menopause symptoms and tretment guidlines and options what are bioidentical hormones?

1. Menopause-symptom relief and
treatment options
Irene Stronczak R.Ph.B.Pharm Hons.
National Certified Menopause Practitioner

2. •Discuss Symptoms of menopause
• Discuss the place in therapy of hormone
replacement and bio-identical hormones in
menopause
• Discuss dosage, formulations, route of
administration, side effects, and contraindications
• Discuss the controversies and appropriate use of
hormone replacement therapy
•Discuss patient case studies
OBJECTIVES

3. HT formulation,route,and timing of initiation produce
different effects
• Absolute risks for HT use in healthy women ages 50-59
are low
• HT initiation in older women carries greater risks
• Breast cancer risk increases with EPT beyond 3-5years
• ET can be considered for longer duration of use because
it carries a lower risk for breast cancer
NAMS 2012 Position Statement
Hormone therapy—what we know today
3

4. • HT may reduce total mortality when initiated soon
after menopause
• Both ET and EPT may reduce total mortality by 30%
when initiated in women younger than age 60
NAMS position statement. Menopause 2012.
HT & Total Mortality
4

5. estrogen/progesterone treatment started soon after
menopause appears to be safe; relieves many of the
symptoms of menopause; and improves mood, bone
density, and several markers of cardiovascular risk.
KEEPS Results Give New Insight Into Hormone
Therapy-2012
5

6. 6
nary Heart Disease / Stroke
and coronary artery risk when initiated in younger and more rec
us
ecommended for coronary protection in women of any age
pear to increase ischemic stroke risk and have no effect on hem

7. Hulley S, et al. JAMA. 1998;280:605-13; Grady D, et al. JAMA. 2002;288:49-57; Blumenthal RS, et al. Am J Cardiol.
2000;85:1015-7.
 The women in HERS were on average 18 years post
menopause, suggesting that years
since menopause may have an important influence on
the cardiovascular effects associated with initiation of
CEE/MPA
 Cardiovascular risks of CEE/MPA in this population
were observed early and
did not occur in individuals taking concomitant statin
therapy
HERS: Lessons Learned
7

8. Therapeutic goal is lowest effective estrogen dose,plus
appropriate progestogen dose for women with a uterus
•Lower doses have fewer side effects and may have more
favorable benefit-risk ratio than standard doses
•All routes of administration of ET can effectively treat
menopausal symptoms
•Transdermal ET may be associated with lower risk of DVT,
stroke, and MI
•Multiple progestogen options for endometrial protection
NAMS position statement. Menopause 2012.
Dose & Route of Administration
8

9. 9

10. Lower daily doses typically used with systemic ET:
 0.3 mg oral CE
 0.5 mg oral micronized 17ß-estradiol
 0.014-0.025 mg transdermal 17ß-estradiol patch
Typical lowest doses of progestogen:
 1.5 mg oral medroxyprogesterone acetate
 0.1 mg oral norethindrone acetate
 0.5 mg oral drospirenone
 50 mg oral micronized progesterone
HT Starting Dosages
10
NAMS position statement. Menopause 2010.

11. No First-pass Effect
Less of an effect on:
- Clotting factors
- Triglycerides
- C-reactive protein
- Sex hormone-binding globulin
Transdermal v oral route
11

12. First line therapy for VMS and for patients with conditions:
- High risk of DVT or PTE - High triglyceride levels - Gall
bladder disease
- Hypertension
2. Need for “steady state” drug release - Daily mood swings
- Migraine headaches - Shift workers
3. Inability to use oral tablets
- Stomach upset
- Problems with taking a daily pill
Consider using transdermal estrogen

13. Transdermal/Topical
 Transdermal mimics the way the ovaries release
hormones.
 No first pass metabolism & metabolites formed.
 Greater chance that hormone gets to target tissue prior to
metabolism
 Steroids are well absorbed through the skin
 Transdermal Estradiol when given with or without oral
progesterone, has no detrimental effects on coagulation
and no observed increased risk for venous
thromboembolism
 Health Canada approved
 Estradiol for women
 Testosterone for men
Delivery System-creams and gels

14.  “It remains possible that transdermal estradiol
with progesterone which more closely mimics
the normal physiology and metabolism of
endogenous sex hormones may provide a
different risk-benefit profile”
 writing group for WHI July 2002
Conclusions of WHI

15. ET alone 1.29 (1.02-1.65)
ET+ other progestin 1.69 (1.50-1.9)
ET+ progesterone 1.00 (0.83-1.22)
ET+ dydrogesterone 1.16 (0.94-1.43)
Estrogen in combination with micronized progesterone =
no increased risk
Ref: Fournier 2008
Breast cancer risk and progestogen
selection

16.  No clear indication that longer HT duration
improves or worsens the benefit-risk ratio
 HT effects on long-term risks have not been
studied in perimenopausal women
 Thus, findings from RCTs of postmenopausal
women should be extrapolated with caution
for younger women
Duration of HT Use
16
NAMS position statement. Menopause 2010.
(cont’d)

17.  Extending HT use is acceptable:
 For women well aware of potential
risks and benefits
 With lowest effective dose
 For prevention of further osteoporosis-related
fracture and bone loss when alternate
therapies are inappropriate or benefit-risk ratio
is unknown
 With clinical supervision
HT Duration of Use (cont’d)
17
NAMS position statement. Menopause 2010.

18.  Moderate to severe vasomotor symptoms have been documented in
42% of women aged 60 to 65 years. Thus, many women will continue to
have vasomotor symptoms after age 65, and these symptoms can
disrupt sleep and adversely affect health and quality of life.Provided that
the woman has been advised of the increase in risks associated with
continuing HT beyond age 60 and has clinical supervision, extending HT
use with the lowest effective dose is acceptable under some
circumstances, such as for the woman who has persistent bothersome
menopausal symptoms and for whom her clinician has determined that
the benefits of menopause symptom relief outweigh the risks
The North American Menopause Society
Statement on Continuing Use of Systemic
Hormone Therapy After Age 65-2015
18
HT should be individualized and not discontinued solely based on a w

19. • Progestogens alone or low-dose oral
contraceptives can be offered as alternatives for the
relief of menopausal symptoms during the
menopausal transition
•E.g.,Oral progesterone 200mg nightly day14-
28 of cycle
SOGC Clincal Practice Guideline, January 2009, JOGC
Progestogens in the Menopause
Transition
19

20.  Mood changes
 Insomnia-60%
 Headaches
 Hot flashes-80%
 Memory problems
 Aches and pains
 Fatigue
 Decreased libido
 Bloating
 Night sweats
Signs and symptoms of hormone imbalance in
patients

21.  Regulates body temp
 Improves insulin sensitivity
 Increases basal metabolic rate
 Increases blood flow
 Improves sleep
 Maintains skin collagen
 Decreases risk of cataracts Increases bone density
 Decreases LDL,increases HDL
 Increases mood and energy
 Decreases wrinkles
 Decreases homocysteine
 Increases serotonin formation
 Decreases depression,anxiety,pain sensitivity
Functions of estrogen

22. Progesterone
 Helps the body use estrogen
 Prevents and treat symptoms of estrogen excess
or deficiency (i.e. vasomotor symptoms)
 Natural antidepressant
 Prevents endometrial overgrowth
 Has receptors in almost every cell of the body
 Progesterone is needed not only for its balancing
effect on uterine tissue, but also its effect on the
breast tissue, heart, brain, bones and its balancing
effect on other hormones.
Functions of progesterone

23. Relief of symptoms
Growth and repair
Prevention of memory loss
Heart health-improved lipid profile
Prevention of osteoporosis
Quality of life
Maintenance of skin health
Neurotransmitter balance
Prevention of urogenital atrophy
WHY REPLACE?

24.  Response to widely publicized results from 2002 WHI
52% stopped HRT-25% restarted for symptom relief
 Suspicion of traditional medicine
 Dislike of big Pharmaceutical companies
 Perception it’s a safer alternative
 “Natural” is equated with safer
 Wider and more aggressive advertising, via internet and other
media-Oprah phenomenon
 Patient preference for alternative medicine.
 Patients still symptomatic on commercial HR products
Why the Surge in Prescriptions for Bioidenticals
from Patient P.O.V.?

25.  Bio-identical hormones have a chemical structure identical to human
hormones but are chemically synthesized from yams or soy and are
identical in composition to human hormones, such as progesterone,
estriol,testosterone and estradiol.
 Natural – neither artificial nor pathologic
 They look and behave just as our own natural hormones do. They
will act at our cell receptors and break down in our cells
(metabolize) exactly the same way as the estrogen and progesterone
naturally made inside our body have always done.
 Non-bioidentical hormones are not structurally identical to human
hormones and may either be chemically synthesized, such as MPA,
or derived from a nonhuman source, such as CEE.
Bioidentical Hormones=Bioequivalent

26.  Chemical substitution with a pharmaceutical
drug, only mimics some hormonal functions
 Ingredients-50%E1,0.5% E2, 40% Horse equilins
 While some estrogens are from a natural
source, such as equine urine, they are not
considered bioidentical because many of their
components are foreign to the human body.
Synthetics- Premarin

27.  Progesterone is the same hormone that is produced and
circulates in your body
 Vital to pregnancy
 Progestins are synthetically produced molecules that
produce the same effects on the endometrium as
progesterone
 Do not have the same structure
 May not function the same as progesterone in other
tissues
 Harmful in pregnancy
Progesterone vs. Progestins
27

28. Evidence
 Oral medroxyprogesterone (MPA) and estrogen
 Increased incidence of breast cancer versus estrogen alone
 Increased heart disease
 Counteracts the vasodilatation of estradiol
 Increase in blood clots, C-reactive protein
 MPA speeds the growth of arterial smooth muscle cells,
whereas progesterone slows this growth
 Norethindrone did not have the same effect
 Oral micronized progesterone (Prometrium®)
 Produces sedating byproducts
 Stabilizes and protects the endometrium from estrogen
 Had less breakthrough bleeding than with MPA
 Same incidence of uterine cancer between MPA and
progesterone
 Premarin® alone increased stroke and clots
Progesterone vs. Progestins
28

29.  Side effects-
 Increased weight
 Fluid retention
 Depression
 Breast tenderness
 Acne
 Insomnia
 Vasospastic
 Increases LDL
Provera is not progesterone

30.  Prometrium
 Crinone,
 Estrace,
 Divigel, Estradot,Climara
Pro,Oescilim,Estalis
 Estrogel,
 Androgel, Testim,Androderm
 Estring,
 Vagifem,Estragyn
 Ovestin-Estriol (OTC, Europe)
 Cortef
 Cytomel (T3)
 Synthroid (T4)
Patented/Conventional
Bio-identical Hormones

31.  Compounded
 Estrone
 Estradiol
 Estriol
 Progesterone
 Testosterone
 DHEA
 Cortisol
 T3
 T4
 Methods of delivery
 Oral
 Topical
 Creams
 Gels
 Sublingual drops, troches
 Vaginal/mucous membrane
 Cream
 Suppository
 Pellets
 SQ injection
Bio-identical Hormones

32. Estrone (E1):
 Second strongest estrogen
 Converted from estradiol & released from adrenal glands
 Main estrogen in menopause-converted from androstenedione in
adipose tissue,liver and skin
Estradiol (E2):
 Strongest estrogen
 Mainly made from the ovary
 Formed by testosterone aromatization
 Primary estrogen in menstrual cycle
Estriol (E3):
 Weakest estrogen, end metabolite of estrogen pathway
 Dominant in pregnancy
 Considered possibly protective from more potent proliferative
effects of E1 and E2
Bio-identical Estrogens

33.  Pharmacy compounding – defined by both Ontario College
of Pharmacy and Pharmacy industry; its core is the “triad”
relationship between the patient, her physician, and the
pharmacy which prepares a prescription for that patient
only upon receipt of a valid prescription
 All pharmacies licensed and inspected-OCP
 Specialized training
 All drugs used have certificate of analysis- USP
 Leave out colourants,additives
 Provide technical help and expertise on dosing guidelines
Pharmacy compounding

34.  History and symptoms may not be enough
 Every patient is biochemically unique
 Get baseline for follow up and optimal balance and treatment
 Low normal may not be optimal for health
 Many labs do not have ‘age specific ranges’
 FSH-does not measure estrogen
 Blood: Estradiol,FSH,free and total testosterone
Thyroid Panel -free T4,TSH, free T3,
Saliva: estradiol , progesterone, testosterone,
DHEAS, and Cortisol
24 hour Urine
Testing-why test?

35. Estradiol
 Can be used alone
 Compounded into SR capsules,
transdermal, topical & vaginal creams-
topical 50-500mcg daily
 Start low go slow
 Priming may be necessary higher dose for
1/12 then decrease
Bio-Identical + Compounded Hormone
Replacement

36. Estriol
 Blocks the more potent effect of
Estradiol at the receptor
 Can be given orally-many studies
 Given alone can help improve urinary
incontinence & vaginal dryness
0.05-0.5% vaginal cream 0.5-1g daily
x1/12 then prn
Bio-Identical Compounded Hormone
Replacement

37. Bi-Est
 Estriol/estradiol combination
 Compounded cream or capsules
 Offers the benefit of estradiol and the
protective effect of estriol
 Strength in mg and ratio of the two
estrogens
 Example: Bi-Est 1.25mg 80:20 = 1.0mg estriol
+ 0.25mg estradiol
Bio-Identical Compounded Hormone
Replacement

38. Progesterone
 Topical and oral (Prometrium→
)
 Usual topical dosage is 20-100mg OD-BID, daily
 Peri menopause cycle days 14- 28 ,or 2 steps day 1-14,day 15-28
 Menopause continuous(stop for at least one day) or cycle
 Oral doses range from 100-400mg daily
 1% cream=10mg/g 1g=1/4tsp
 Progesterone metabolites may cause a tranquilizing effect
 SOGC does not recommend progesterone cream to provide
endometrial protection
 Maintain endometrial stripe on U/S<4mm
 Expect 1-2 periods if starting cyclic progesterone within 6 months of
menopause
 May cause increase in testosterone
Bio-Identical Compounded Hormone
Replacement

39. Testosterone:
 ↑ sense of wellbeing and libido
 Helps maintain vaginal mucosa, skin
elasticity, muscle mass & heart health
 Compounded into creams or gels
 Range 0.05-1%=0.5-10mg Testosterone/ml
Bio-Identical Compounded Hormone
Replacement

40. Vaginal lubricants
•May be recommended for subjective symptoms
•Do not reverse vaginal atrophy
Are non-physiological
•Give temporary symptom relief, often followed by
vaginal irritation
Vaginal Moisturizers and Lubricants
40

41. • Polycarbophil gel is effective for
symptoms of vaginal atrophy
• Improve lubrication
Do not reverse vaginal atrophy
• Are useful for women who cannot take hormones
vaginal moisturizers
41

42. Restore urogenital physiology
- > Estrogen therapy lowers vaginal pH, thickens the
epithelium, increases blood flow, improves vaginal
lubrication
- Alleviate symptoms
• > Most women will obtain substantial relief from their
symptoms after about 3 weeks of treatment
Some women may require 4–6 weeks before adequate
improvement is observed
Principles of local estrogen therapy (supported by
NAMS and SOGC)
42

43. 1. Start treatment early,before atrophic changes have
occurred.
2. Continued treatment is needed to maintain the
benefits.
3.All local estrogen preparations are effective.
4.Patient preference will usually determine the treatment
that is used.
5.Additional progestin is not indicated when appropriate
low- dose, local estrogen is used. If estrogen is
ineffective or undesired, vaginal lubricants and
moisturizers can relieve symptoms due to dryness.
IMS Key Treatment Recommendations
43

44.  Dehydroepiandrosterone (DHEA) is an
androgen derivative that is available in Canada
by prescription only[ It has been evaluated
intravaginally for effectiveness in treating VVA
and is thought to exert an effect through the
androgen and estrogen receptors.The 12-week
trials showed improvements in VMI and vaginal
pH at 2 dosesV3.25 mg and 13 mg, once daily.
It also significantly improved the most
bothersome symptoms.
 Intravaginal DHEA
44

45. 1 Several selective serotonin reuptake inhibitors (SSRIs) and
serotonin norepinephrine reuptake inhibitors (SNRIs) decrease the
frequency and severity of vasomotor symptoms in postmenopausal
women.
2 The SSRI paroxetine is the first nonhormonal medication to be
government approved for the treatment of vasomotor symptoms.
The approved dose (paroxetine 7.5 mg) is lower than the doses of
paroxetine approved for the treatment of depression.
3 Although randomized, controlled trials demonstrate efficacy
greater than placebo for other SSRIs and SNRIs, including
venlafaxine and escitalopram, and other doses of paroxetine, these
formulations are not currently approved for the treatment of
vasomotor symptoms.
4 Some SSRIs and SNRIs inhibit the cytochrome P450 enzyme
system and may render tamoxifen less effective.
SELECTIVE SEROTONIN REUPTAKE INHIBITORS AND
SEROTONIN NOREPINEPHRINE REUPTAKE INHIBITORS
45

46. Applying Hormone Creams
GeneralTips
 Absorption is better in moist skin than dry
 Shower and pat dry, then apply
 Absorption is better in thin skin than thick
 Apply to soft skin (inner forearm, inner thigh)
 Apply to a large area
 Rub in well
 Consider a 3-5 day break for progesterone every month to decrease
tolerance
Location
 Testosterone may cause hair growth on the inner thigh
 Progesterone on the breast may decrease the tissue density
 Estrogen on the breast can cause proliferation .: avoid
 Hormone creams applied to the abdomen will be absorbed to the
liver

47.  Compounded BHT may be just as effective as commercial
HT
 BHT may be safer and as effective as synthetics-although non
human not as bad as we thought
 Compounded BHT should be just as safe as commercial HT
 Research often puts all HRT together ,regardless of type or
dosage form used
 Research supports use of BHRT
 Topical estrogen over oral estrogen
 Avoid synthetic progestins
 More research needed to support optimum dosing and
testing of compounded creams
The Likely Bottom Line on BHRT

48.  All hormones are designed to work together
 Use same hormones as body produces
 Be informed and educated
 Develop a partnership with the pharmacist
 If one hormone is deficient it affects actions of all
other hormones-thyroid Cortisol
 Determine each patients needs and goals-stress
nutritional deficiencies
 Follow up and testing needed
 One size does not fit all
SUMMARY

49.  Valuable option – Not the Holy Grail
 Individual pharmacies should produce
consistent product
 Studies on compounded BHRT usually
terrible-more becoming available
 Studies by Big Pharma often skew data
 Too many people who are involved don’t
know enough (public & professionals)
My perspective on Compounded BHRT

50.  44 yo female
 Pmh-tah,b/o 2006
 Rx-ogen3mg daily,oxycocet prn,
 c/o insomnia,low libido,low energy,25lb weight gain,night
sweats,hot flashes,mood swings,migraine headaches,
 Labs-free testosterone,<0.5,estradiol 49
 Tx-Prometrium 100mg po hs,testosterone 5mg topically,Bi-est
1.5mg daily topically
 f/up estradiol 107,free T 5
sleep improved,weight decrease,mood better,d/c Ogen,night
sweats rare,hot flashes one every 2-3 weeks,no
headaches,’DID NOT THINK THIS WOULD WORK”
Patient case

51. 20 August 2006
Patient Case Study
 KE 34 yo female 5’3” 140lbs
 Symptoms-
– Insomnia, weight gain, anxiety, hot
flashes, painful intercourse, mood
swings
– Goals & priorities-I want to feel as
good as I possibly can without
synthetic hormones
 Medical hx-TAH BSO hypothyroid,
interstitial cystitis, endometriosis,
arthritis
 Medications-Thyroxine, Premarin
 Vitamins-Multivitamin
 Lifestyles-
– Exercise-Pilates, walking,
outdoor sports
– Smoking-quit 1994(8yrs)
– Alcohol-social
– Caffeine-occasionally
 Family hx- mother ovarian
cancer, diabetes (uncles)

52. 20 August 2006
Lab Results & Treatment Recommendations
 28/05/05-
– TSH=6.00,E2=389,DHEA-S=2.4
– Restart thyroxine
 11/09/05-
– Free T <1,Total T=4.7,P=1.09
– Tx-testosterone 1.0% 1ml daily
– Progesterone 200mg daily
 9/01/06-
– E2=107,TSH=3.35,free T=4.0
 Pt reports a world of difference ,lost
12lbs,no naps ,less joint aches ,some
breast tenderness
 Decrease Premarin to 1 every other
day
 02/02/06-
– E2=79,free T=4.9,P=41.4
 07/04/06-
– Pt c/o skin breakouts
– Decrease T to every other day, add
saw palmetto 2 x a week
 22/06/06
– Pt c/o some decreased libido
– TSH=2.17,E2=138,P=12.5,Free T=2.0
– Replace Premarin with Biest (80/20)
1.0mg bid topically, Testosterone 1%
1.0ml daily/alternating with 0.5mls