Dr. Gibbons and Dr. Cummings offer recommendations on treatment and management options that can help you navigate this important life transition.

1. Management of Common
Menopausal Complaints
Alice B. Gibbons, MD
Summit Medical Group
February 12, 2014

2. Vasomotor Symptoms=Hot Flushes
• Estrogen alone or combined with
Progesterone, 75% reduction in flashes
• Orally or transdermally, in patches, gels and
sprays
• Low dose also effective; Ultra low dose not
effective, and not FDA approved
• Risks are thromboembolic disease and breast
cancer

3. Women’s Health Initiative Study, 1999
•
•
•
•
Primary focus was heart disease prevention
Average age of study participants was 63
Women had no menopausal symptoms
Women hadsignificant other medical
problems
• Maybe estrogen was triggering events in
patients who already had atherosclerosis?
• Study ended prematurely

5. • Synthetic products
• Binds to many receptors giving side effects (fluid
retention, acne, weight gain, sugar intolerance)
• Can cause anxiety/irritability in central nervous
system
• Blunts estrogen’s favorable impact on lipids
• Stimulates breast cells
• Constricts blood vessel, increases heart disease

6. • Post WHI 2002:
• 50% decline in conventional hormone therapy
prescriptions in first 6 months
• Many patients turned to compounded therapy
• Many chose alternative therapies
• Discontinuation of HT-50% have recurrent
symptoms.
• No guidelines on discontinuing abruptly or
tapering

7. FDA Clearly States
“Other doses of estrogens and
progestins and other combinations
were not studied in the WHI trials,
in absence of data these risks
should be assumed to be similar”

8. Kronos Early Estrogen
Prevention Study (KEEPS) @ 2007
• Purpose: to evaluate progression of
atherosclerosis which causes heart disease
• Four year trial in women aged 42-58 with a
uterus, started on estrogen within 3 years of
menopause
• Received one of three treatments with
progesterone:
Oral estrogen, Transdermal, or Placebo
Brain Research 2013;1514:12-17

10. North American Menopause Society
2012 Position Statement
• Individualization is of key importance in the decision to
use HT and should incorporate the woman’s health and
quality of life….as well as her personal risk factors.
• The recommendation for duration of therapy differs
for EPT and ET. For EPT, duration is limited by the
increased risk of breast cancer associated with 3-5
years of use; for ET a more favorable risk profile during
a mean of 7 years of use, allows more flexibility in the
duration of use
•
Menopause 2012;19(3):257-271

11. Global Consensus Statement on HRT (2013)
• Key Conclusions
• Benefits outweigh risks for women under 60 or
within 10 years of menopause
• HRT is effective for symptoms related to
menopause such as hot flashes, sleep, bone
health.
• Taking HRT should be individualized and made
in consultation with a qualified physician.
•
Maturitas 2013;74:391-92.

12. •
Bioidentical (native) Some are FDA approved
• “Natural”- found in nature, derived from pregnant mares urine
(thus the name Premarin)
Estrone sulfate (human bioidentical)
Equilin sulfate (native to horses)
• Synthetic- made in a laboratory, broken down in stomach to be
estradiol

13. What does it mean to be a bioidentical hormone?
– Derived from plants
– Claimed to be similar to human hormones, i.e. acts
like estrogen and progesterone
– Sometimes used to treat menopause symptoms
– Not from an animal, not synthetic (man-made)

14. FDA-approved Hormones for Menopausal Symptoms
Type/source
Estrogens
Brand name(s)
Form
Bioidentical?
Pill
No
Vaginal cream
No
Conjugated equine estrogens
(CEE)/pregnant mares’ urine
Premarin
Synthetic conjugated estrogens/plants
Cenestin, Enjuvia
Pill
No
Esterified estrogens/plants
Menest
Pill
No
Estrace, others
Pill
Yes*
Alora, Climara, Esclim,
Estraderm, Vivelle,
others
Patch
Yes
Estrogel
Transdermal gel
Yes
Estrasorb
Topical cream
Yes
Estrace
Vaginal cream**
Yes
Estring
Vaginal ring**
Yes
Ortho-Est, Ogen, others
Pill
No
Ogen
Vaginal cream**
No
Estradiol acetate
Femring
Vaginal ring
Yes
Estradiol hemihydrate
Ethinyl estradiol
Vagifem
Estinyl
Vaginal tablet**
Pill
Yes
No
17 beta-estradiol/plants ++Micronized
(Particles are made smaller for better
absorption)++
Estropipate (modified estrone)/plants

15. Progestins, micronized progesterone
Medroxyprogesterone acetate (MPA)
Brand Name
Form
Bioidentical
Amen, Cycrin, Provera
Pill
No
Prometrium
Pill
Yes
Prochieve 4%
Vaginal gel
Yes
Norgestrel
Ovrette
Pill
No
Norethindrone
Micronor, Nor-QD, others
Pill
No
Norethindrone acetate
Aygestin, others
Pill
No
CEE and MPA
Premphase, Prempro
Pill
No
Ethinyl estradiol and norethindrone acetate
Femhrt
Pill
No
Activella
Pill
No
Combipatch
Patch
No~
17 beta-estradiol and norgestimate
Prefest
Pill
No~
17 beta-estradiol and levonorgestrel
Climara Pro
Patch
No~
Micronized progesterone USP
Combined hormones
17 beta-estradiol and norethindrone acetate

16. – Compounded* bioidentical hormones NOT FDA
approved
• Considered a dietary supplement
• No rigorous testing required
– As a dietary supplement, the burden for the FDA is
to prove it is unsafe rather than effective
*Compounded hormone = mixed by pharmacists as prescribed by practitioners

17. B
I
E
S
T
• Estradiol- reproductive age
• Estrone-present in menopause
• Estriol-present in pregnancy,
very weak
T
R
I
E
S
T

18. • Estriol not available as single agent tablet in
USA, required to have “new drug” application
for FDA approval
• No safety studies for Biest or Triest
• No studies showing native hormones prevent
bone loss

19. Popular prescription method
• Variable dose over 28 day cycle
• Topical Application
Background on Wiley
• Author but not a physician
• No supporting scientific data

20. • “Ultrafiltrate” of blood; should be able to
measure free hormone available
• Measures deficiencies in order to customize
PROBLEMS
• No agreement between blood and saliva levels
• Saliva levels vary with diet and time of day
(need to measure 5x/day)

21. Dosing according to symptom response, NOT
blood levels. End points:
• Control of vasomotor symptoms (hot
flushes)
• Reversal of vaginal atrophy (dryness)
• insomnia improvement
FDA has not approved any bioidentical
combination product

22. Compounded
Products
FDA-Approved
Products
Failed ≥ one quality tests
34%
<2%
Failed Potency analyses
90%
.13%

23. COMPOUNDED PROGESTERONE
for menopausal symptoms
May not protect uterine lining
Doesn’t prevent osteoporosis,
Doesn’t eradicate symptoms,
so why would we use it by itself?

24. TESTOSTERONE
• Patch used for Hypoactive Sexual Desire
Disorder
• Increase in number of satisfying sexual
episodes from .5 (placebo) to 2.1(testosterone
patch)
• May change lipid profile unfavorably
Blood tests inaccurate in women
Again, not FDA approved

25. In patient’s with uterus in place, means taking two products,
and therefore, more cost
FDA products more likely to be covered by insurance
Compounded products more expensive overall
Conflict if doctor also selling product
More likely to be offered to economically more advantaged
Women seek it out to restore sexual well-being; may be
psychologically more vulnerable

26. •
•
•
•
•
Other Useful Agents-not estrogens
Progesterone alone may help hot flashes when used
alone, but safety unclear
Testosterone alone not FDA approved, shows no benefit
and has male hormone side effects. When used with HT,
improved sexual function scores
Clonidine- medication to lower BP, not FDA approved
for menopause symptoms
Gabapentin (Neurontin) anti-seizure, 45% effective in
studies, not FDA approved
SSRIs-anti depressants-Paroxetine (Paxil) is ONLY nonhormonal therapy that is FDA APPROVED

27. •Anti-depressant, not a hormone
•Hot flashes decreased by 55% in Lexapro group, 35% in
placebo group
•Women felt that 1.4 fewer hot flushes/day was a meaningful
improvement
•Similar result to other drugs in this category-area of exploration
•Strong placebo effect which means non-medical factors were
Important
JAMA.2011;305(3):267-274. doi:10.1001/jama.2010.

28. Selective Estrogen Receptor Modulators (SERMs)
Definition:
Synthetic compounds that selectively stimulate or inhibit the estrogen
receptors of different target tissues
Estrogen receptors in different target tissues vary in chemical structure
Example: Tamoxifen: inhibits breast tissue, but stimulates uterus
Evista: inhibits breast tissue, stimulates bone,
neutral on the uterus
New Product Bazedoxifene
Negative on the uterus, stimulates bone

29. Brand New: HT/SERM combination product known as a
Tissue Selective Estrogen Complex (TSEC)
Ideally, this combination would have the positive
attributes of both drug categories with fewer
undesirable side effects.
Alleviates hot flushes (estrogen)
Treat vaginal dryness (estrogen)
Protect against bone loss (both)
Would not stimulate the uterus (serm)
Does not require Progesterone (serm)

30. Estrogen with
Bazedoxifene
Duavee is
expected
to be
available in
February
2014

31. Alternative Therapies for
Menopausal Hot Flushes
• Phytoestrogens-plants substances with estrogenic biologic
activity-no benefit, not detrimental, not studied well
• Vitamins-limited data; Vitamin E (800 IU) effect was one less
hot flush/day
• Acupuncture-no benefit over placebo
• Reflexology-no benefit over foot massage
• Exercise-no significant improvement in hot flushes, but sense
of well-being
• Decrease alcohol and caffeine-slight benefit
• Placebo alone can have significant impact on flushes

32. • Good Manufacturing Practices (GMPs)-companies
must comply
• US Pharmocopeia (USP)
• National Sanitation Foundation (NSF)
• ConsumerLab-manufacturer can pay to have
product tested and listed on website
(Consumerlab.com)
• Although there is some supervision of this industry,
not sufficient data to support use for menopause
symptoms

33. Generally,
no overall
benefit

34. Possible
benefit,
no benefit,
or
inconclusive

35. Hormonal Treatment of Vaginal Dryness
and Painful Intercourse
• Local therapy in form of creams, rings, and vaginal
tablets (Estring, Estrace, Vagifem…)
• Local therapy does not require progesterone to
protect uterine lining
• May actually help urinary symptoms
• Patients with previous history of breast cancer often
eligible for vaginal estrogen after consultation with
oncologist

36. Vaginal Lubricants
• Lubricants reduce friction and pain related to
dryness during sex
• Moisturizers trap moisture and provide long
term relief- may reduce irritation, improve
acid-base balance

37. Ospemifene (Osphena) for
Vaginal Dryness
•
•
•
•
Oral product, SERM category of drug
Estrogen receptor stimulant on vaginal tissue
Does not stimulate the uterine lining
FDA approved for treatment of moderate-to-severe
dryness causing painful sex
• Side Effects: hot flushes, vaginal discharge, excessive
sweating
• Benefit: easy to take tablet

38. Even though
FDA approved;
Note large
boxed warning

39. Sleep Hygiene
Sleep only as much as you need to feel refreshed the next day
•Maintain a regular sleep and wake pattern 7 days a week.
•Avoid napping during the day; it can disturb the normal pattern of
sleep and wakefulness
•Avoid stimulants, such as caffeine, nicotine and alcohol, too close to
bedtime.
•Exercise can promote good sleep. Vigorous exercise should be taken
in the morning or late afternoon. A relaxing exercise, like yoga, can be
done before bed to help initiate a restful night’s sleep.
•Food can be disruptive right before sleep; stay away from large meals
close to bed time.

40. More Sleep Hygiene
•
Associate your bed with sleep and sex only. It is not a good idea to use your bed
to watch television, listen to the radio or read.
• Make sure that the sleep environment is pleasant and relaxing. The bed should
be comfortable and the room should not be too hot, too cold or too bright.
• Establish a relaxing bed time routine. Try to avoid emotionally upsetting
conversations and activities before trying to go to sleep.
• Do not take your problems to bed. If necessary, plan some time earlier in the
evening for working on your problems.
• If you are unable to sleep, do not try harder and harder to fall asleep. Instead,
turn on the light, leave the bedroom and do something different, like reading a
boring book. Do not engage in stimulating or productive activity. Return to bed
only when you are sleepy. Get up at your regular time the next day no matter
how little you slept.
• Do not look at clock, turn it away
Source; Modified from the Thoray M Sleep hygiene; a new era CPAP therapy.
Arlington (VA): National Sleep Foundation; 2003.

42. • More specific binding to JUST progesterone
receptors
• Mild diuretic
• Mild sedative effects (helps sleep)
• No effect on lipids
• Does not stimulate breast
• Relaxes blood vessels, decreases plaque
formation

43. Legal History:
1994
Dietary Supplemental
Health & Education Act
2008
2010
FDA Enforcement
Action
Dietary Supplement Full
Implementation & Enforcement Act