Transcript Hormonal Changes at 50

Hormonal Changes at
50
Josephine Carlos-Raboca, MD, FPCP,FPSEM
Section of Endocrinology, Diabetes & Metabolism
Makati Medical Center
Outline
Menopause: Physiology
Treatment:
nonhormonal
hormonal
Andropause:Physiology
Treatment:
Testosterone
Growth Hormone
Summary
Menopause Overview
Menopause is a natural part of a woman's life
cycle.
monthly periods end.
freedom from pregnancy and additional childraising responsibilities.
Effects of Menopause
Vasomotor instabilityhot flashes, and
waking during the night
Mood changes -Mood swings; depression or
anxiety
Cognitive function- decreased verbal memory
Sexual function - libido
Urogenital - dryness, itching, pain during
sexual intercourse sudden or frequent urinating
Menopause Increases Women's
Risk for Osteoporosis
women can lose up to 5 percent of their bone
mass per year in the first 5 years following
menopause.
Risk of Cardiovascular Disease Also
Increases after Menopause
The risk of CVD increases in women after
menopause
By age 60 heart disease becomes as common in
women as in men.
Managing Menopause
Healthy lifestyle to protect against osteoporosis
and cardiovascular disease
Maximize medications for these conditions
A balanced diet, calcium and vitamin D;
Weight reduction if overweight;
Stop smoking;
Weight-bearing exercise
Yearly mammogram and breast examination
Treating the Symptoms of Early
Menopause:
Individual counseling or support groups
Vaginal moisturizers such as Vagisil or Replens.
Lubricants, such as K-Y Jelly or Astroglide
Low-dose vaginal estrogen
Lack of desire may be helped with more open
communication with your partner.
Creating a pleasurable atmosphere at home and
making a point to enjoy other activities with
your partner .
Treating the Symptoms of Early Menopause
with Non-Hormones:
Selective-Serotonin Reuptake Inhibitor (SSRI) drugs
and Serotonin Norephinephrine Reuptake Inhibitor
(SNRI) drugs.
Gabapentin
Medroxyprogesterone acetate and megestrol acetate,
progesterone-type drugs.
Clonidine
Changing Aspects of Hormone
Replacement Therapy
Conventional rationale for HRT
derived from favorable outcomes of
observational
studies
in
perimenopausal women
Recent randomized clinical trials
showed potentially adverse effects
of HRT in late postmenopausal
women
RCTs results have discouraged HRT
use in perimenopausal women
Benefits of HRT
Relief of menopausal symptoms
Increase bone density
CVD benefit ?
Improve memory?
Improve sexual function?
Youthful look?
Decrease colon cancer
Decrease macular degeneration
Women's Health Initiative 2002
The largest randomized prospective trial
evaluating the effects of estrogen plus progestin
and estrogen alone versus placebo (no
hormone).
WOMEN’S HEALTH INITIATIVE CLINICAL TRIAL
( WHI – US )
OBSERVATIONAL, CLINICAL CORHORT
150,00 POSTMENOPAUSAL WOMEN
GRP 1 - 48,000 WOMEN
Objective : To evaluate the efficiency of Low Fat diet in the prevention
of breast , colorectal cancer and coronary heart disease.
GRP 2 - 45,000 WOMEN
Objective : To evaluate the effect of Calcium &Vitamin D in fractures
and colorectal cancer.
GRP 3 - 27,500 WOMEN
Objective : To assess HRT’s efficacy in the prevention of
cardiovascular diseases and fractures .
Estrogen in Osteoporosis
Prevention of bone loss and fragility fracture
WHI – 33% reduction in fracture ratethe only
therapy with efficacy data on prevention of
fracture in women with osteopenia
Alternate Treatments Are Available
Non-hormonal treatments to prevent and treat
osteoporosis bisphosphonates, elective estrogen
receptor modulators (SERMs), parathyroid
hormone (PTH) calcitonin.
HRT and Risk of Cardiovascular Disease
The increase in risk following menopause
suggests that estrogen made by the ovary prior
to menopause may protect against heart
disease.
However, recent studies have shown no benefit
to the use of postmenopausal hormone therapy
in heart disease prevention and indicate the
need to use other modalities to help women
fight heart disease.
HERS II
Results from extended, open-label evaluation of
the
HERS
(Heart
Estrogen/progestin
Replacement Study) indicate no cardiovascular
benefit of HT in postmenopausal women with
previous history of cardiovascular disease
JAMA 2002
WHI and CVD risk
Estrogen + Progestin
increased CVD by 29%
Estrogen only in hysterectomized
no increase in CVD risk
Estrogen+Progestin Therapy and Risk of CHD:
Results According to Time Since Menopause
Women’s Health Initiative – E+P trial
Women <10 years since menopause: RR=0.89
Women 10-19 yrs since menopause:
RR=1.22
Women 20+ years since menopause:
RR=1.71
(But no modifying effect of age)
Manson JR et al NEJM 2003
Reducing Risk of CVD
Statins have been shown to lower the risk of
CVD in individuals with abnormal circulating
lipids and those who have a family history of
heart disease.
Small doses of aspirin daily
HRT and cognitive function
WHI Memory Study (WHIMS)
Women aged 65 or older who took estrogen
plus progestin had twice the rate of dementia,
including Alzheimer’s disease, as those taking
placebo. Estrogen plus progestin did not protect
against mild cognitive impairment (e.g., trouble
paying attention and remembering).
JAMA 2003
Cognitive function
The Women's Health Initiative data suggest that
women who initiate hormone therapy at age 65
or older have worsening dementia than women
who take no hormones.
Until more is known, hormone therapy cannot
be recommended for prevention of Alzheimer's
disease.
Other Benefits
Taking estrogen plus progestin lowers the risk
of developing colon cancer by 37%
Taking estrogen lowers the risk of developing
age-related
macular
degeneration,
a
degeneration of the retina of the eye.
Risks of HRT
Stroke
WHI 39% increased in E
41% increased in E+P
Breast cancer
WHI no significant increase in E
26% increased in E+P
Venous thromboembolism 47%
"Designer Estrogens"
Selective
Estrogen
Receptor
Modulators
(SERMs). Act as beneficially as estrogen on
some tissues and as estrogen-blockers on
other tissues
Tamoxifen-used to prevent breast cancer
Raloxifene - used to prevent osteoporosis,
Selective estrogen tissue
Tibolone
Commonly Used Alternatives
to Hormone Replacement Therapy
Black CohashCamomileChasteberryDong QuaiGinsengLicorice RootSt. John's WortValerianSoy Products
Testosterone/DHEA
Supplement in Women
Not approved
Variable to no benefit
Data shows benefit
in hypopituirarism,
premature
ovarian
failure,
bilateral
oophorectomy and primary adrenal insufficiency
Conclusion 1
Short-term hormone therapy is approved by the
U.S. Food and Drug Administration in younger
women for some symptoms of menopause,
including hot flashes, vaginal dryness and
painful intercourse
the lowest effective dose possible.
Individualized and time dependent
WHAT IS ANDROPAUSE? (Late Onset
Hypogonadism) [PADAM / ADAM]
A
clinical
condition
characterized by a partial
deficiency of androgens in
blood and/or decreased
testosterone availability to
various systems or organ
functions.
Clinical Symptomatology
Usual appearance of young men
Typical
appearance of
testosterone
deficiency
Recent Insights into the Andropause
Low testosterone levels affect mood, vitality, sexuality
brain: decreased libido
depressed mood
heart: increase in cardiovascular risk
muscle: decrease in strength & mass
kidney: anemia due to < erythropietin
production
bone: decreased bone mineral density
sexual organs: erectile dysfunction
Endogenous Androgen
Production
Testes: >95%
 testosterone
Adrenals: <4%
 dehydroepiandrosterone
Pathophysiology
Testosterone decreases with aging
SHBG increases with aging with a decrease in
bioavailable testosterone
Decline in testicular Leydig cells
Due to abnormal hypothalamic –pituitarytesticular axis
Testosterone Replacement:
Is it necessary?
IMPROVEMENT OF
SXS OF
ANDROPAUSE
BPH AND PROSTATE
CANCER RISK
CV EVENTS, ETC
Osteoporosis
Not just a female disease!
25–30% of hip fractures occur in men!
Serious ! 25% die of it in the short term
25% die of it in the longer term
Only 20% return to their former quality of life;
many more need assistance 51 % suffer from
depression (Cowith activities of daily living
olsaet, Aging Male congress 2002)
Gooren L Lecture Int. Symposium of Andropause Society, London, 2003
Bone Mineral Density (Lumbar Spine) after 36 Months
of Testosterone Treatment in 70 Elderly Men
(mean age 71, T<350 ng/dL)
12
BMD-% Change from Baseline
* p<0.05
*
10
8
*
*
6
Placebo (n = 24)
*
4
T (n = 24)
*
2
0
-2
0
6
12
18
24
30
Month
Amory JK et al. J Clin Endocrinol Metab 89(2): 503-510 (2004)
36
Body Composition,
Strength and Function
Role of testosterone
Increases nitrogen retention
Increases protein synthesis
Bhasin (NEJM, 1996)
TRT dose related increase in skeletal muscle
mass and strength
In a systematic review of 6 trials T reduced fat
mass and increased lean body mass
Testosterone Improves Physical Performance
in 70 Elderly Men (mean age 71, T<350 ng/dL)
change in grip strength from baseline (kg)
T (n=24)
*
*
Placebo (n=24)
*
*
24 mo
36 mo
*
*
*
baseline
*p<0.05
12 mo
left
24 mo
36 mo
baseline
12 mo
right
Page ST et al. J Clin Endocrinol Metab 90(3): 1502-1510 (2005)
TRT and Depression
• Testosterone decreases with advancing age in
males
• Lower bio-T in depressed aging males
• Testosterone deficiency and depression
symptoms overlap, current treatments are often
insufficient for depression
• The use of testosterone for depressed
hypogonadal males (with documented low BioT) holds promise
Margolese, HC, J Geriatr Psychiatry Neurol 2000; 13:93-101.
Sexual Function
Jain Meta-analysis (J Urol, 2000)
TRT 57% overall improvement rate for ED
TRT improved nocturnal erection and penile rigidity in
hypogonadal males (Cunningham 1990, J Clin Endoc Metab; Arver, 1996 J
Urol)
TRT –direct vascular effect on the corpora cavernosa
mediating nitric oxide effects (Aversa 2003, Clin Endocrin)
TRT potentiates libido by a central effect and erection
by central and peripheral effects
Hematopoietic Effects of TRT
Red Blood Cells
T stimulates erythropoietin secretion by the
kidneys and bone marrow RBC precursors
Indications for testosterone substitution
Symptoms of hypogonadism and
morning testosterone levels below 12 nmol / l
Absolute contraindications for
testosterone substitution
Prostate carcinoma
Desired paternity (for secondary hypogonadism,
gonadotropin administration is required)
Relative contraindications for
testosterone substitution
Benign prostate hyperplasia, sleep apnea, polycythemia,
criminal sexual behavior
Nieschlag and Behre, Andrology, 2000, Springer
Conclusion 2
Late Onset Hypogonadism can lead to
dysfunction of multiple organ systems and
detriment of the quality of life of the aging male
Diagnosis can be made by clinical and
biochemical parameters
Testosterone replacement is indicated in
carefully selected patients and leads to
improvement of symptoms
Can Growth Hormone Prevent Aging?
NEJM Volume 348:779-780 February 27,
2003 Number 9Next
Mary Lee Vance, M.D.
The Bottom Line
on growth hormone
Although growth hormone levels decline with
age, it has not been proven that trying to
maintain the levels that exist in young persons
is beneficial. Considering the high cost,
significant side effects, and lack of proven
effectiveness, HGH shots appear to be a very
poor investment. So called "growth-hormone
releasers," oral "growth hormone," and
"homeopathic HGH" products are fakes.
Summary
Menopause and Andropause are characterized
by decreasing sex hormones and clinical
features that go with it.
Hormone replacement in men and women has
benefits and risks.
Hormone replacement should be used in the
perspective of current available data.
“ In the autumn years of life , a
woman or a man deserves an
Indian summer rather than a
winter of discontent .“
by : Robert Greenblatt