Transcript October 2011 MENOPAUSE SLIDE SHOW

Perimenopausal Women’s
Health: A Practical Evidence
Based Review
Annemarie M. Kallenbach
Adult Nurse Practitioner
thePracticalNursePractitioner.com
Annemarie M. Kallenbach
Adult Nurse Practitioner
225 Riverside Dr
Adrian MI 49221
517 263 1800
Annemarie Kallenbach
Adult Nurse Practitioner
Perimenopause
women’s health care
is based on scientific
data across ethnicities
Large Studies
• SWAN - Study of Women’s Health Across
the Nation
• NHS - Nurse Health Study
• HERS - Heart and Estrogen Progestin
Replacement Study
• SEAS - Soy Estrogen Alternative Study
• WHI - Women’s Health Initiative
• California Teacher’s Study
Women’s Health Initiative
SEA isoflavonoids found in soy protein
(specifically genistein)
• Have many properties that may reduce the risk of
coronary heart disease.
• Favorable effects on plasma lipids and coronary
artery vasomotion.
• Genistein is a tyrosine kinase (TK) inhibitor with
inhibitory effects on thrombin activity and TK
receptor-linked mitogens that may be associated
with atherogenesis and neointimal formation after
angioplasty.
BCCP and WISEWOMAN
Well–Integrated Screening and
Evaluation for Women Across
the Nation
Participate in a Study on
Hot Flashes
• This study will evaluate an investigational nonhormonal drug to treat hot flashes. Candidates
must be 40 or older, post menopausal, and have
seven-to-eight moderate-to-severe hot flashes in a
24-hour period.
• The research site is in Katy, Texas.
• More information
http://www.clinicalconnection.com/clinical_trials/
condition/hot_flashes.aspx
Menopause Perception
• Cessation of menstrual cycles / End of
reproductive ability
• A time of hormonal changes
• A change of life
• A changing body
• A time of changing emotions
• An aging process
Menopause – Physiology
• Cessation of menstrual cycles
– Follicular depletion ("natural"
menopause)
– Surgical removal of the ovaries
("induced" or "surgical," menopause)
– The secretion of the ovarian hormones
estrogen and progesterone ends with
menopause
Menopause - Sociology
Graduate school at research based
Women’s Center
vs
Searching google
Perimenopausal Changes
•
•
•
•
•
•
•
•
Reproductive
Cognitive?
Vasodilatation
Genitourinary/sexuality
Skin
Skeletal
Cardiovascular
Increased cancer risk
Periomenopausal - Reproductive
Contraception is necessary until the woman
has been amenorrheic for one year
Periomenopausal - Reproductive
Irregular heavy bleeding may occur
Treatment options
NSAIDS
OCP
Mirenia
Ablation
Hysterectomy
Perimenopauseal
Cognitive symptoms / changes
• Chronic sleep disturbance
• Contribute to fatigue, irritability
and reduced concentration
• No evidence actual mental change
caused by menopause
Osteoporosis Risk Factors
• Reduction in estrogen production with
menopause is the major cause of loss of
BMD during later life.
– Timing of menarche, absent or infrequent
menstrual cycles, and the timing of menopause
influence both the attainment of peak bone
mass and the preservation of BMD.
Osteoporosis Risk Factors
Large Prospective Studies
• MORE Multiple Outcomes of Raloxifene
Evaluation
• FIT
Disease prevention
Colon Cancer
• Age great than fifty need screening
Disease prevention
Colon Cancer
• HRT reduces incidence of colon cancer by
50%
• Adding aspirin further reduces incidence
• Probiotic and fiber
Disease prevention
Breast Cancer
• Age great than fifty need screening yearly
Perimenopausal Treatment
Reproductive
• Switch from OCP to HRT
• Take of OCP while still menstrating, Use manual method of BCP and
when no menses for a year start HRT
• Consider Mirenia
• Check FSH:LH ratio on day 7 of placebo week at the age of her
mother’s menopause.
• Of the FSH:LH ratio is >1 switch patient to HRT
• Check FSH level after 1 week off COCs at age 50 and annually
thereafter
• An FSH level of >30 indicates you can start HRT
NATURAL APPROACHES TO
MENOPAUSE
http://judynolanivil.tripod.com/id27.html
Perimenopausal Treatment
Cognitive
• Systematic review
• Based on the available evidence, ERT or
HRT cannot be recommended for overall
cognitive improvement or maintenance in
older postmenopausal women without
cognitive impairment.
Lethaby A, Hogervorst E, Richards M, Yesufu A, Yaffe K. (2008).
Hormone replacement therapy for cognitive function in
postmenopausal women. Cochrane Database Syst Rev. Jan
23;(1):CD003122.
Perimenopausal Treatment
Anxiety
• SSRI used for vasodilation
KAVA
•
•
•
•
Prospective randomized
40 women surgical menopause anxiety
HRT with vs without Kava
With Kava demonstrated significantly lower
anxiety.
De Leo V, et al. Evaluation of combining kava extract with hormone
replacement therapy in the treatment of postmenopausal anxiety.
Maturitas 2001;39:185-8.
Perimenopausal Treatment
Anxiety
Kava
• 60-150 mg/day
• Caution with Benzodiazepam
Perimenopausal treatment –
Vasodilation
Phyto-Female Complex
Rotem C, Kaplan B. Phyto-Female Complex for the relief of hot
flushes, night sweats and quality of sleep: randomized, controlled,
double-blind pilot study. Gynecol Endocrinol. 2007;23(2):117-22.
Soy food chart
Food
Amount
Grams
Soy Milk
1 cup
7
Tofu
4 oz
10
Soy nuts
¼ cup
17
Perimenopausal treatment –
Vasodilation
SSRI
Perimenopausal- Vasodilation• Oral clonidine, 0.1 mg/d, is effective against
tamoxifen-induced hot flashes in
postmenopausal women with breast cancer.
Pandya KJ, Raubertas RF, Flynn PJ, Hynes HE, Rosenbluth RJ, Kirshner
JJ, Pierce HI, Dragalin V, Morrow GR. (2000)Ann Intern Med. 2000
May 16;132(10):788-93.
Perimenopausal -VasodilationGabapentin
Toulis KA, Tzellos T, Kouvelas D, Goulis DG. (2009). Gabapentin for
the treatment of hot flashes in women with natural or tamoxifeninduced menopause: a systematic review and meta-analysis. Clin
Ther. Feb;31(2):221-35.
Perimenopausal-Vasodilation
Isoflavones
Tice JA, Ettinger B, Ensrud K, Wallace R, Blackwell T, Cummings SR.
2003. Phytoestrogen supplements for the treatment of hot flashes:
the Isoflavone Clover Extract (ICE) Study: a randomized
controlled trial. JAMA. Jul 9;290(2):207-14.
Perimenopausal Treatment Vasodilation
Black cohosh and St. John’s wart
Uebelhack R, Blohmer JU, Graubaum HJ, Busch R, Gruenwald J,
Wernecke KD. (2006). Obstet Gynecol. 2006 Feb;107(2 Pt 1):247-55
. Mahady GB, Fabricant D, Chadwick LR, Dietz B. (2002) Black cohosh:
an alternative therapy for menopause? Nutr Clin Care. 2002 NovDec;5(6):283-9.
UIC/NIH Center for Botanical Dietary Supplements Research, Program
for Collaborative Research in the Pharmaceutical Sciences, University
of Illinois, Chicago, Illinois, USA.
Black cohosh
• Current recommended dose is 40-80 mg per
day. ($1-2/day)
• At least 4-12 weeks of treatment may be
required before any therapeutic benefits
may be apparent
Perimenopausal treatment
Vasodilation
• Soy isoflavones – Genistein and diadzien
• Recommendation soy isoflavones 600mg a
day for PMS
• 100mg BID perimenopause
• Some cautions with breast cancer
• $1/day
www.wholehealthmd.com
OP Estrogen vs. Risendronate
vs. Isoflavones
• Only soy isoflavones from the cotyledon
and germ significantly decreased net bone
resorption by 9% (P = 0.0002) and 5% (P =
0.03), respectively.
• Calcium absorption and biochemical
markers of bone turnover were not
influenced by interventions.
Osteoporosis – SERM,
biphosphinates, teriparatide
• Only raloxifene appeared to reduce the risk of vertebral
fracture in postmenopausal women unselected for low
bone mineral density (BMD).
• None reduce the risk of non-vertebral fracture in women
unselected for low BMD.
• These net costs were markedly different by age, with some
interventions becoming cost-saving at higher age ranges in
patients with a prior fracture.
Stevenson M, Jones ML, De Nigris E, Brewer N, Davis S, Oakley. (2005). A systematic
review and economic evaluation of alendronate, etidronate, risedronate, raloxifene
and teriparatide for the prevention and treatment of postmenopausal osteoporosis.
J. Health Technol Assess. 2005 Jun;9(22):1-160.
Natural health products
Osteoporosis:
• Systematic review of randomized controlled trials
• Some intial support for treatment of osteoporosis
• Osteoporosis treatment with evidence: Calcium;
copper; fish oils; fluoride; magnesium;
manganese; strontium; vitamin D;
Whelan AM, Jurgens TM, Bowles SK (2006.)Ann Pharmacother. 2006
May;40(5):836-49. Epub 2006 May 2.
NHP
• Algaecal Plus
– $1/day
• Fish oil – animal and in vitro studies only
for osteoporosis
Osteoporosis
• Despite the effectiveness of therapy, most patients
who receive treatment do not remain on treatment
for >1 year.
• Develop strategies to improve treatment
continuation rates.
Gass M, Dawson-Hughes B. (2006). Preventing osteoporosis-related
fractures: an overview. Am J Med. 2006 Apr;119(4 Suppl 1):S3-S11.
Soy isoflavone – Blood glucose
Might have a favorable effect on Fasting
glucose
No significant effect on serum lipids.
Ho SC, Chen YM, Ho SS, Woo JL. (2007). Soy isoflavone
supplementation and fasting serum glucose and lipid profile
among postmenopausal Chinese women: a double-blind,
randomized, placebo-controlled trial. Menopause. 2007 SepOct;14(5):905-12.
Disease prevention –
Atherosclerotic Heart Disease
• Control of HTN
• Management of Diabetes
• Control of Lipid Elevation
Perimenopausal Treatment - Skin
• A 5-10% cream containing DHEA has been
used up to four weeks.
Calvo E, et al. (2008). Pangenomic changes induced by
DHEA in the skin of postmenopausal women. J Steroid
Biochem Mol Biol. Dec;112(4-5):186-93. Ann
Pharmacother. 2006 May;40(5):836-49. Epub 2006 May 2.
Perimenopausal Treatment –
Vaginal Atrophy/Incontinence
• Vaginal Estrogen
• Progesterone is not indicated / Insufficient data to
recommend annual endometrial surveillance
• Continue as long as distress symptoms occur
• Same for women with non hormone dependent cancer
• For those with hormone dependent cancer individual
decison with onc.
• Practitoner pearl – used around urethral meatus improves
incontinence.
• NAMS Statement
ZESTRA Borage seed oil, Evening primrose oil,
Angelica root extract, Coleus forskohlii extract,
ascorbyl palmitate, and dl-alpha tocopherol.
Statistically significant improvements in
level of sexual arousal, sexual desire,
genital sensation, ability to have orgasms,
and sexual pleasure.
Ferguson DM, et al. Randomized, placebo-controlled, double-blind,
crossover design trial of the efficacy and safety of Zestra for Women
in women with and without female sexual arousal disorder. J Sex
Marital Ther 2003;29 Suppl 1:33-44
ArginMax Asian Ginseng Gingko Damiana L-Arginine
Vitamins A, C, E, and B-complex Calcium Iron Zinc Selenium
• Improvement in sexual desire in women
Ito TY, Trant AS, Polan ML. A double-blind placebo-controlled study of
ArginMax, a nutritional supplement for enhancement of female sexual
function. J Sex Marital Ther 2001; 27(5):541-9. J Sex Marital Ther
2001; 27(5):541-9.
HRT
Traditional method
• Continuous estrogen and progestin
Vs
• Cyclic continuous estrogen plus progestin
for only 10-14 days per month
HRT
• Conjugated (synthetic) estrogen - is a
combination of nine estrogens and is similar
to conjugated estrogens (Premarin. Unlike
the estrogens in Premarin which are
obtained from the urine of pregnant horses,
the estrogens in Cenestin are synthetic
(man- made) and are produced from plant
material (soy and yam)
• $4/day vs $3/day
HRT Triple Estrogen or Tri-Est
• A combination of E1,E2 and E3
• No data to say it is better
• Bioidentical difficult because no
real way to measure individual
• Can be compounded
HRT
• Dose HRT at bedtime
– Maximum level 4-6 hours after ingestion
– Coincide with peak time for hot flushes and
sleep disturbances
– Usually occur around 3 - 4 am
HRT Patch
• Better menstrual hemostasis
– Rate of amenorrhea at 12 months
• 94% patch
• 86% oral
• Increase tissue sensitivity in diabetes
• No increase risk for venous thrombosis
• Less adverse effects on triglycerides
• $10/day
HRT Progesterone Creams
• Pro-Gest OTC, made from Mexican wild
yarms or soybeans
• No better for breast CA
• No studies have proved it use
• Dose 1/4 to 1/2 teaspoon into palms, belly
or shoulders twice a day
• 4oz on Amazon $19.00
Vaginal estrogen
• Progesterone is not indicated
• Insufficient data to recommend annual endometrial
surveillance
• Continue as long as distress symptoms occur
• Same for women with non hormone dependent cancer
• For those with hormone dependent cancer individual
decison with onc.
• Practitoner pearl – used around urethral meatus improves
incontinence.
• NAMS Statement
HRT and Androgens
• Estratest
–
–
–
–
Continued hot flushes relief
Increase libido (Increased 80%)
Decrease HDL
Dose related hirsuitism
• Transdermal Testosterone
• Not FDA approved
• Off label -300 mcg twice a week
SERM
• Raloxifene (Evista)
• Invasive Breast cancer protection
• Has not been found to cause spotting or menstrual-like
bleeding nor to increase the risk of cancer of the lining of
the uterus.
• $4/day
• Lasofoxifene and arzoxifene are two newer SERMs that
have recently been demonstrated to improve bone mineral
density and lower serum cholesterol values
Clarke BL, Khosla S. (2009). New selective estrogen and androgen
receptor modulators. Curr Opin Rheumatol. 2009 Jul;21(4):374-9.
HRT
• Doses of HRT are 4X lower than OCPs
Osteoporosis Treatment
Exercise
• Strong evidence that physical activity early
in life contributes to higher peak bone mass.
• Some evidence indicates that resistance and
impact exercise are likely the most
beneficial.
Osteoporosis
Calcium and Vitamin D
• Ca++ 1,000 to 1,500 mg/day
– Only about 50 to 60% meet recommendation
• Recommended vitamin D
–
Intake of 400 to 1000 IU/day
• High dietary protein, caffeine, phosphorus, and
sodium can adversely affect calcium balance
– effects less important in individuals with
adequate calcium intakes.
DHEA
• For improving bone mineral density in people with
weak bones (osteoporosis): 50-100 mg per day.
• Long terms studies unknown
• Side effects as other hormones: acne, greasy skin,
menstrual irregularities, coagulopathies (CA,
worsen chol, DM)
• Internet cost $2/day
OP RX treatment
Biphosphonates - valid studies
• Alendronate, $2.5/day $25/week
• Risedronate $4/day $133/mo
• Ibandronate $150/mo
Osteroporosis treatment
•
•
•
•
Teriparatide (Forteo)
20mcg SC
600mcg=948.26
$30.00 day
OP RX treatment
Salmon calcitonin Miacalcin®
• Positive effects on BMD at the LS but not hip
• Nasal calcitonin no FX data
• .50/day $130/bottle
HRT
Breast Cancer Risk
• Observation period of 5-6 years, several clinical trials reported an
increased risk of breast cancer due to hormone replacement therapy
(HRT).
• It appears more likely that HRT stimulates the growth of already
existing small tumor nests which - due to their small size - would
otherwise go undiagnosed.
• In summary, HRT is hence more likely to be a tumor promoter than a
de novo-inducer of breast cancers.
Dietel, M. 2010. Maturitas. 2010 Hormone replacement therapy
(HRT), breast cancer and tumor pathology.
Mar;65(3):183-9. Epub 2009 Dec 14.
Breast Cancer Risk
• Greatest after 5 years
• No increase with short term use <2 years
• Micronized progesterone may be safer
Fpirmoer A et al (2009). Timing of HT, progestogen type and breast
cancer: The French E3N Study. J Clin Oncol 27:5138
Prevention daily ground flax seed
Hormone Products USA and
Canada
• http://www.menopause.org/htcharts.pdf
NAMS Position Statement 2010
Recent data support the initiation of HT around the
time of menopause to treat menopause related
symptoms; to treat or reduce the risk of certain
disorders, such as osteoporosis or fractures in
select postmenopausal women or both. The
benefit-risk ratio for menopausal HT is favorable
for women who initiate HT close to menopauses
but decreases in older women and with time since
menopause in previously untreated women
NAMS 2010 Osteoporosis
• Osteoporosis –
• Evaluation medical history, physical exam
and diagnostic tests
• Risk factors advanced ge, genetics, lifestyle
factors (low ca and Vit d, smoking )
thinness and menopause status.
NAMS Osteoporosis
• Most common risk factors balanced diet
adequate calcium and vit d, adequate
exercise smoking cessation avoidance of
excessive alcohol intake and fall prevention
• Gov approved options are bisphophonates,
SERS parathyroid home estrogens and
calcitonin
Integrative Medicine
• About Herbs, Botanicals & Other
Products
• This information resource, presented by our
Integrative Medicine Service, provides
evidence-based information about herbs,
botanicals, supplements, and more.
http://www.mskcc.org/mskcc/html/11570.cfm
Wellness promotion
Physical
• Normalization of weight
• Regular exercise
– Flexibility
– CV
– Calorie expenditure
• Sleep Hygiene
• Dietary Intervention
Wellness promotion
Physical
Diet rich in fruit vegetables, whole grains,
nuts and low fat dairy products low in
saturated fat, cholestesterol, sugar and
refined carbohydrates,(e.g DASH) decrease
systolic blood pressure and increase quality
of life.
Daily Nutrient Goals Used in the DASH Studies
(for a 2,100 Calorie Eating Plan)
Total fat: 27% of calories
Saturated fat: 6% of calories
Protein: 18% of calories
Carbohydrate: 55% of calories
Cholesterol: 150 mg
Sodium: 2,300 mg*
Potassium: 4,700 mg
Calcium: 1,250 mg
Magnesium: 500 mg
Fiber: 30 g
* 1,500 mg sodium was a lower goal tested and found to be even
better for lowering blood pressure. It was particularly effective for
middle-aged and older individuals, African Americans, and those
who already had high blood pressure. g = grams; mg =
milligrams