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3/10/2014
T. WATSON JERNIGAN, MD MA NCMP
Associate Dean of Clinical Affairs
 I, T. Watson Jernigan,
DO NOT have a financial
interest/arrangement or affiliation
with one or more organizations
that could be perceived as a real
or apparent conflict of interest in
the context of the subject of this
presentation.
I, T. Watson Jernigan,
DO anticipate discussing the
unapproved/investigative use of a
commercial product/device
during this activity or
presentation.
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The participant will demonstrate an
understanding of the physiology of the
hormone, TESTOSTERONE
The participant will appreciate the use of
testosterone including the benefits and the
side effects of the therapy
The participant will understand the FDA’s
stance on the use of testosterone in
postmenopausal females
The use of testosterone in patients has been
discussed since the late 1890s.
Recently, there have been restrictions placed
on the prescribing of testosterone-containing
hormonal therapies.
This lecture will look at the physiology of
testosterone and the value it has in treating
diminishing hormonal values in
postmenopausal patients.
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It is hoped that the lecture will update the
practitioner on the current views on the use
of testosterone in postmenopausal patients.
It is also hoped that the lecture will give
insight as to the current state of literature on
the use of testosterone.
Finally, it is hoped that the lecture will allow
the practitioner a better handle on
discussions by patients regarding the use of
testosterone.
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In women, the production of testosterone
occurs in several sources
There is direct secretion by the ovaries and to
a small extent by the adrenal cortex
The majority of circulating testosterone
derives from peripheral conversion of
androstenedione (approximately 50%)
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Prepubertal testosterone levels in girls is very
low and increase substantially around the
time of puberty
During reproductive age women, there is a
slight increase at the midcycle though minor
in nature
After menopause, the testosterone levels
decrease up to 15% over several years
However, this decline is gradual compared to
the rapid decrease in estradiol levels at the
same timeframe
In women, testosterone circulates in the
blood bound to three proteins
60% by volume of testosterone is tightly
bound to Sex Hormone Binding Globulin
(SHBG)
Most of the remainder is bound to albumin
and a small amount bound to corticosteroidbinding globulin
Only approximately 1% of total volume of
circulating testosterone remains unbound or free
in women
The adrenal gland preferentially secretes weak
androgen such as Dehydroepidandrosterone
(DHEA) or its sulfated depot form, DHEAS
Androstenedione is the only circulating androgen
with higher levels in premenopausal women than
men though its androgenic potential is only 10%
that of testosterone
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Total testosterone levels do not differ
significantly in any cycle between older and
younger women
Data from the Rancho Bernardo Study
suggest that reductions in testosterone levels
at menopause may be transient and are
followed by normalization in older women
Androstendione levels do decline with age
specifically in the early reproductive years
with a flattening out in midline and a small
increase in later years
Development of acne can occur around the
Menopause due to an increase in the ratio of
androgen to estrogen
In women with acne levels of circulating
androgens are significantly higher than in
women without acne
This leads to the phrase, “Ah, midlife, hot
flashes and acne!”
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Some women experience thinning of hair on
the scalp or unwanted growth of hair on face
in midlife
This phenomenon has been called
Androgenic Alopecia or Female Pattern Hair
Loss (FPHL)
Actual cause is unknown
Several factors have been implicated in the
development of FPHL
FPHL starts with thinning of hair mainly on
the crown of the scalp and widening through
the central hair part
Estrogen and Androgen receptors have been
found in hair follicles
At menopause, there is a decrease in
protective effect of estrogen and a change in
the estrogen to androgen ratio (as levels of
androgens do not significantly change)
Normal postmenopausal changes lead to a
hypoestrogenic and relative hyperandrogenic
state causing an increase in the androgen to
estrogen ratio
This increased ratio may (like noted
previously) lead to changes including the
formation of FPHL
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In a 2008 study published in Endocrine
Regulation by Dr. Riedel-Baima a group of
premenopausal women with FPHL were
evaluated
The ratio of androgen to estrogen was
significantly higher than in the control group
This was suggested as the trigger for the hair
loss
ACNE
HIRSUTISM (FACIAL AND BODY HAIR)
VOICE DEEPENING
ALOPECIA
LIVER TOXICITY
CLITORAL ENLARGEMENT
ADVERSE EFFECTS ON LIPOPROTEINS
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DSM-IV conceptualizes sexual disorders as
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Four types of sexual disorders
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“disturbances in the process that characterize
the sexual response cycle or by pain
associated with sexual intercourse”
Sexual Disorders:
(1) Sexual Desire Disorders
(2) Sexual Arousal Disorders
(3) Orgasmic Disorders
(4) Sexual Pain Disorders
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DSM-IV-TR definition of Sexual Interest &
Desire Disorder: “Absent or diminished
feelings of sexual interest or desire, lack of
sexual thoughts or fantasies, and more
importantly, a lack of RESPONSIVE desire,
absent or scarce motivation for attempting to
become sexually aroused, and a level of
disinterest beyond the normative lessening
routinely associated with life cycle and
relationship duration
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Hypoactive Sexual Drive is the persistent or
recurrent deficiency (or absence) of sexual
fantasies or thoughts and/or the lack of
receptivity to sexual activity
Sexual Arousal Disorder is the persistent or
recurrent inability to achieve or maintain
sufficient sexual excitement, expressed as a
lack of excitement or a lack of genital or
other somatic responses
Most prevalent sexual disorder for women of
all ages
Prevalence of HSDD in women in US today
ranges from 12-19%
Segraves & Woodard: 5.4% to 13.6%
West et al: 8.3%
PRESIDE: 8.9% (18-44); 12.3% (45-64); 7.4%
(65+)
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Diagnosis can be helped with checklist:
little or no interest in sex
decreased vaginal lubrication
persistent genital arousal
difficulty reaching orgasm
pain during sex
partner sexual dysfunction
relationship dissatisfaction
decreased arousal or feelings of
excitement
2000 article by Shifren et al compared two
doses of Testosterone patch versus placebo
therapy
Seventy five women s/p bilateral
oophorectomy were recruited for study
Eighteen (18) were removed from the study:
6 for adverse effects (3 on placebo patch); 6
for personal reasons; 6 for poor compliance
with telephone diary
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Participants were evaluated with: Brief Index
of Sexual Functioning for Women; a
telephone-based diary (daily during 28 days
of base-line period and at least 28 days
during the treatment period); and the
Psychological General Well-being Index
Other parameters including looking for side
effects of testosterone were performed
All participants were without ovarian tissue
and therefore did not have ovarian
production of androgens
All participants were on standard oral
conjugated equine estrogen 0.625 mgs daily
Although participant was on oral estrogen,
their baseline score on the Brief Index of
Sexual Functioning for Women was markedly
impaired
Baseline values of Free Testosterone and
Bioavailable Testosterone were obtained
Normal Range Free T: 1.3-6.8 pg/ml
Baseline Free Testosterone: 1.2 +/- 0.8
pg/ml
On 150 ug patch therapy value of Free T was
found to be 3.9 +/- 2.4 pg/ml
On 300 ug patch therapy value of Free T was
found to be 5.9 +/- 4.8 pg/ml
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Mean (+/- SD) Composite score on Brief
Index of Sexual Functioning for Women:
Baseline : 52 +/- 27
Placebo Treatment: 72 +/- 38
150 ug Testosterone Treatment: 74 +/- 37
300 ug Testosterone Treatment: 81 +/- 37
300 ug vs. Placebo P value = 0.05
Psychological General Well-Being Index:
Baseline (+/- SD): 78 +/- 15
Placebo: + 1 +/- 14
150 ug Testosterone: +2 +/- 14
300 ug Testosterone: +5 +/- 14
Increases in vitality, positive well-being,
depressed-mood, and anxiety subscales on
testosterone treatment
Results demonstrated Hirsutism and Acne
scores DID NOT change significantly during
treatment
Frequency of moderate or severe hot flashes
was unaffected by testosterone treatment
Lab values including total cholesterol, highdensity lipoprotein cholesterol, low-density
lipoprotein cholesterol, triglycerides, fasting
glucose or insulin, liver-function tests, or
blood counts were not significantly effected
by testosterone
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In a May 2005 article in Obstetrics and
Gynecology, Buster et al evaluated the use of
a 300 ug testosterone patch in patients with
HSDD and who had undergone hysterectomy
and bilateral oophorectomy
The study was a 24 week, multicenter,
double-blind, placebo-controlled randomized
prospective study on 533 women
The patients were randomized to placebo
patch therapy or a 300 ug testosterone patch
changed twice weekly
Primary efficacy endpoint was total satisfying
sexual activity measured by the Sexual
Activity Log
Secondary measures included using Profile of
Female Sexual Function and Personal Distress
Scale
Other evaluated items: hormone levels and
adverse events
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Results were based on 206 women in the placebo
group and 211 women in the testosterone patch
group
Total Satisfying Sexual Activity significantly
improved in the testosterone patch group
compared to placebo group; improved sexual
desire; and decreased personal distress
No meaningful changes in mean levels of lipids,
lipoproteins, carbohydrate metabolism markers,
renal function, liver function or hematology
measures were observed in either group
In November 2008, Davis et al published a
study in the NEJM evaluating testosterone in
patients NOT TAKING ESTROGEN
814 women with HSDD were enrolled in a 24
week double-blind, placebo-controlled trial
The participants received either placebo
patch, 150 ug testosterone patch or 300 ug
testosterone patch
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None of the participants were receiving either
estrogen or estrogen + progestin
Primary end point: change from baseline to
week 24 in frequency of satisfying sexual
episodes
Other items evaluated were: hormone levels,
adverse events including breast cancer, and
lipoprotein levels`
Both testosterone groups showed significant
increases in sexual desire and decreases in
distress
In the 300 ug testosterone group, there was a
statistically significant in frequency of
satisfying sexual episodes over placebo
group; 150 ug testosterone group did not
reach statistical significance
The groups did not differ significantly with
respect to serum lipid or lipoprotein profiles,
liver function, or other lab tests
The most common adverse events were
application-site reactions and androgenic events
Overall incidence of androgenic adverse event
was higher in the 300 ug testosterone group and
most commonly was increased hair growth
However, in the testosterone group 4 patients
were diagnosed with breast cancer compared to
0 cases in the placebo group [including one case
diagnosed after 4 months of the study period]
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Previous attitudes toward sex
No available partner
Age-related changes
Perception of their body
Health concerns
Stressors
Medications
Lastly, Estrogen and Androgen Levels
Changed
2002 Princeton Consensus Panel
Pattern of clinical symptoms: diminished
sense of well-being or dysphoric mood;
persistent, unexplained fatigue; and sexual
function changes such as decreased libido,
sexual receptivity, and pleasure in the
presence of decreased bioavailable
testosterone and normal estrogen status
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Additional findings:
bone loss
decreased muscle strength
decreased cognitive function
no other causes for persistent symptoms
Symptom definition: Low libido, blunted
motivation, fatigue, lack of well being
Biochemical definition: Low serum
bioavailable testosterone level with a normal
estradiol concentration in associate with the
above named symptoms
It is still not clear which subfraction or
metabolite of testosterone is most associated
with sexual function
Syndrome characterized by:
1.) Variable cluster of symptoms, some
nonspecific, and without validated measures
2.) Biochemical definition hampered by low
assay sensitivity, a lack of defined population
norms, a lack of clear correlation with specific
measures of sexual dysfunction
3.) An imprecise understanding of the
relationship of androgens to sexual function
in women, leading to uncertainty about what
to measure
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North American Menopause Society (NAMS)
position statement on the role of testosterone
therapy in Postmenopausal women: There is
consistent evidence that in postmenopausal
women with sexual complaints, adding either
oral testosterone or testosterone given by
other routes of administration to estrogen
therapy results in positive effects on sexual
function, primarily an increase in sexual
desire
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Key components of Treatment
(1) Reestablishing Intimacy
(2) Changing sexual routine
(3) Sensate-Focus exercises
(4) Use of Female-Centered Erotica
(5) Development of Sexual Fantasies
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From 2005 article, $19 Billion spent in USA
treating incident fractures with a projection
that this will rise to $25 Billion by 2025
30% of the $ spent now go to LONG TERM
CARE
In a 2002 study, it was estimated that
180,000 nursing home admissions are
related to osteoporosis yearly
Yet only 44% of women who sustain nonvertebral fractures have “osteoporosis” by
BMD
Over 90% of hip fractures due to falls and
about 6% of US medical expenditures are for
older adults due to fall-related injury
In North America, approximately 1/3 of
women over the age of 60 fall at least once a
year
In patients over 75, this rate goes to >40%
per year
Muscle Strength declines in advancing
age…by 65, 33% in men and 45 % in women
Decline in Muscle Strength is much greater
than the Decline in Muscle Mass
A proposed term for this age-related gradual
loss of muscle mass, strength and function:
SARCOPENIA
While multifactorial in nature, one proposed
treatment is anabolic steroids
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