Testosterone Deficiency and Supplementation for Women: What Do

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Testosterone Deficiency and Supplementation for
Women: What Do We Need to Know
Susan Rako, MD
Testosterone: The Foundation
for Sexual Function
Each woman has her own
particular adjustment to the
sexual aspect of life, with
her familiar rhythms of
sexual feelings, fantasies,
dreams, and activities. Life
circumstances can certainly
disrupt sexual rhythms, but
the bottoming out of sexual
desire that results from a
critical reduction in
testosterone is different
from the fluctuations
experienced with the various
ups and downs of life and
relationships.
It has been postulated
that “No matter how hard a
woman might try to
assemble the building blocks
of healthy sexual functioning
– the required amounts of
other hormone, a loving
partner, adequate
stimulation, possibly a good
sexual fantasy – it cannot
work if
she does not have the basic
foundations of enough
testosterone.”
Gallup Survey Data
Reflects
Patitent/Physician Lack of
Knowledge
The results of a Gallup
survey that was conducted
by The North American
Menopause Society (NAMS)
and polled a random sample
of 833 women between the
ages of 45 and 60 on
women’s knowledge,
Information sources, and attitudes
to menopause and hormone
replacement therapy (HRT)
demonstrated that “the majority of
women have heard about estrogen
and progestins, with only a
minority reflecting knowledge
about androgens.” This research
concluded that “these data may
reflect lack of physician knowledge
or information about androgen and
another area for improved provider
and consumer education.”
Androgens, rather
than estrogens, are
responsible for sexual
desire in the human
female
Only 5% of the women polled
knew that their bodies make
“androgens” and that production of
these hormones declines after
menopause. Today, increasing
numbers of peri- and postmenopausal women (many of whom
have had a surgical or chemical
menopause) are approaching their
healthcare providers with questions
about testosterone deficiency and
supplementation.
The Role of Testosterone in
Female Physiology
Testosterone plays a vial role in the
normal physiology of women. In
girls, as well as boys, it is
testosterone that triggers the events
of puberty. The adolescent girls’
growth of pubic and of axillary hair,
the heightened sexual sensitivity in
nipples and genitals, and the
increased susceptibility to
psychosexual stimulation(sexual
libido) are all generated by a surge
of testosterone at adrenarche ( the
markedly increased production of
adrenal cortical androgens that
occurs at puberty).
Groundbreaking research
published in 1959 made use of
clinical observations of women with
advanced breast cancer whose
ovaries and adrenal glands had
Been removed in the hope of
slowing progress of the disease.
This research concluded that
androgens, rather than estrogens,
are responsible for sexual desire in
the human female.
Two years later, another research
study emphasized that “androgen is
the libido hormone in both men and
women’ and that estrogen was
“necessary to abolish vaginal dryness
and tenderness and so expedite
coitus” – but the androgen was
found to increase the sensitivity of
the genitals, especially the clitoris,
as well as the heighten desire and
increase sexual gratification.
Other Effects
Testosterone, an anabolic steroid
and the most potent of the
androgens, promotes metabolic
efficiency, the physiologic basis for
the maintenance of “vital energy”. It
has been stated that “testosterone
and other androgens have some
biological activity on virtually every
tissue in the body.
Symptoms and Signs
of Testosterone Deficiency
…………………………….
1. Global loss of sexual desire:
lack of sexual fantasy and
sexual dreams.
2. Decreased sensitivity to
sexual stimilation in the
nipples and in the clitoris.
3. Decreased arousability and
capacity for orgasm.
4. Diminished vital energy and
sense of well-being.
5. Loss of muscle tone.
And in Women
6. Thinning and loss of pubic
hair.
7. Genital atrophy not
responsive to estrogen.
8. Dry and brittle scalp hair;
dry skin.
Testosterone and Bone
Density
Recent research has shown that
testosterone contributes
substantially to bone density, as
well as to muscle tone. Results of a
two-year investigation that
compared the effects of oral
estrogens (1.25 mg of conjugates
estrogens) and a combination
estrogen/methyltestosterone
preparation (2.5 mg of
methyltestosterone and 1.25 mg of
conjugated estrogens) on
menopausal symptoms, lipidlipoprotein profiles, and bone
density in surgically menopausal
women were published in 1995.
This study confirmed the
effectiveness of testosterone on
menopausal symptoms and
demonstrated that the oral
combination not only prevented
hone loss – as did estrogens alone –
but also produced significant
increases in spinal hone mineral
density – an effect not produced by
estrogens alone.
Testosterone Production in
Women
On the average, premenopausal
females produce .3 mg of
testosterone per day. With the
establishment of the menstrual
cycle, the hormone primarily
produced by the ovaried is
androstenedione, most of which is
then converted to testosterone and
subsequently aromatized to
estadiol. However, not all of the
ovarian testosterone becomes
estradiol. Enough testosterone
remains unconverted to amount to
25% of a woman’s daily
testosterone production, another
25% is produced by the adrenal
cortex, and the remaining 50% by
peripheral tissues (including the
liver, the skin, and the brain) from
precursors produced in the ovaries
and the adrenals. In other words,
the ovaries and the adrenal glands
produce all of a woman’s
testosterone – directly or
indirectly.
Testosterone in the Blood
Most of the circulating testosterone
(97-99%) is carried in the blood
bound to sex hormone binding
globulin (SHBG). Only unbound or
“free testosterone (1%-3% of the
total) can attach to cellular
receptors to produce effects on
tissues. If a woman is not using
supplementary methyltestosterone,
accurate values for both total and
free testosterone can be obtained
when measuring testosterone blood
levels. Available assays for total for
testosterone are confounded by the
presence of methyltestosterone,
although the assay for free
testosterone are confounded by the
assay for free testosterone can be
used as an indicator to gauge the
serum level of testosterone attained
at a given supplemental dosage of
methyltestosterone.
Sensitivity to testosterone is a
variable phenomenon – function of
the levels and thresholds for activity
of testosterone receptors, which are
in turn influenced by estrogen
levels. The adequacy of a particular
blood level of testosterone can
differ from woman to woman. A
woman presenting with the clinical
symptoms and signs of testosterone
deficiency and whose blood levels
of total and free testosterone are
measured to be in the lower part of
the “normal” range may actually be
testosterone deficient and will
benefit from appropriate
supplementation. In this regard, it
is preferable to “treat the patient,
and not the number.”
Physiological Levels of Serum
Testosterone in Women
 Total Testosterone 25 –
70 ng/dl
 Free Testosterone 0.7 –
2.0 pg/ml
Menopause, Adrenopause,
and Testosterone Deficiency
The postmenopausal ovary
produces not only markedly lower
amounts of estrogens, but
substantially lower amounts of
testosterone in 50% of women.
Several years before most women
reach menopause (by 40-44)
adrenal androgen production has
already decreased by more than
half.
Since the function of the adrenal
cortex appears to be linked to the
function of the ovary, a woman
needs fully functioning ovaries in
order to maintain fully functioning
ovaries in order to maintain fully
functioning adrenals. This
fascinating fact may be related to an
embryological phenomenon: one
original group of cells is the source
for both the ovaries (or testes) and
for the adrenal cortices. In other
words, in the developing embryo,
cells migrate from one original
group – some to form the gonads,
and others to form the adrenal
cortices.
Following menopause women
lose not only a significant
Portion of their ovarian
estrogen and testosterone, but
also a significant portion of
their adrenal androgens,
including testosterone
It was long been observed that
adrenal cortical hormone
production (including testosterone)
falls off more quickly in women
than in men. This may be due to
the fact that, on average, the testes
remain functional for decades
longer than the ovaries. The
consequence of the connection
between ovarian function and
adrenal function is that, following
menopause; women lose not only a
significant portion of their ovarian
estrogen and testosterone, but also
a significant portion of their adrenal
androgens, including testosterone.
In some naturally menopausal
women, testosterone production
may decrease to the point where it
is unmeasurbale; signs and
symptoms of testosterone
deficiency can develop for these
women even during their
perimenopause. More commonly,
testosterone deficiency develops
during the several years following
natural menopause. Since estrogen
has the effect of stimulating the
production of SHBG (which will
bind up more of whatever available
testosterone a woman may be
producing), when a woman takes
estrogen supplemental therapy, she
may be tipped into testosterone
deficiency – with loss of libido,
energy, and other symptoms.
Early publications on the role of
testosterone in female physiology
described menopause as “a catabolic
stat.” To maintain healthy tissue
and as healthy a metabolic balance
as aging allows, for many
menopausal women HRT means:
 Supplementary estrogen,
 Progestin (if needed to
protect against
endometrial hyperplasia),
and
 Testosterone
Hysterectomy and
Testosterone Deficiency
In 1993, the most recent year for
which statistics are available,
561,000 hysterectomies were
performed in the U.S. Today more
than 30% of American women have
had a hysterectomy – most often
before the age of 50. The Gallup
survey conducted by NAMS yielded
the statistic that of the 833 women
polled, 37.5% had a hysterectomy.
Even though one or both ovaries
may be spared at the time of
surgery, ovarian failure (postulated
to be a consequence of interruption
of the blood supply formerly
provided by the uterine artery)
follows hysterectomy in a
significant number of cases.
Within a few days to a few weeks
of the surgery, women whose
ovaries have been surgically
removed or compromised can
develop dramatic symptoms both of
estrogen and testosterone
deficiency. Supplementary
estrogen, which is often prescribed,
cannot help the symptoms of loss of
sexual libido and response, lack of
general energy, and diminished
sense of well-being that are the
consequence of the testosterone
deficiency that approximately half
of these women develop.
Studies have demonstrated that
women who had undergone surgical
menopause and were treated both
with supplemental estrogen and
testosterone achieved an optimal
balance of sexual energy and wellbeing, as compared with women
given wither no hormones or
estrogen alone.
At a time when they may be
enjoying their sexual and vial
energies to the fullest, women who
undergo hysterectomy in their 30s
and early 40s (and occasionally,
even in their 20s) are particularly
unprepared for the aggrieved by
these losses. Too often the
diagnosis of testosterone deficiency
is missed, and many women
reporting loss of libido and energy
are prescribed antidepressants or
referred for counseling; however,
what they actually need it
supplementary testosterone.
Chemical Menopause and
Testosterone Deficiency
The 1992 publication of: “A
Neglected Issue: The Sexual Side Effects
of Current Treatments for Breast Cancer”
addressed the fact that women who
have lost ovarian function secondary
to chemotherapy for cancer develop
testosterone deficiency. Symptoms
include:
 Global loss of sexual desire
 Diminished sexual
pleasure and fantasy
 Decline of clitoral
sensations and
 Markedly diminished
orgastic response.
Similar to the population of
women suffering the hormonal
consequences of surgical
menopause, a significant number of
women who become testosterone
deficient following chemotherapy
are in their 30s and 40s. On the
basis of the available data with
regard to estrogen supplemental
therapy for women who have had
breast cancer, increasing numbers
of oncologists believe that the
benefits outweigh the risks.
While there is controversy
among oncologists with regard to
the prudence of testosterone
replacement for women with breast
cancer, the publication noted that
some oncologists “do not hesitate to
prescribe the low does of
testosterone that are libido
restorative,” particularly in t he face
of the results of several studies that
suggest that “androgens may
actually be indicated and
therapeutic for patients with this
neoplasm.”
Even though they know that
definitive research data is not
available, chemically menopausal
women can be so distressed by their
symptoms of testosterone
deficiency and compromised quality
of life that they choose to take
prudently prescribed
supplementary testosterone. To
improve the quality of the life they
have remaining, some women
whose cancer has already
metastasized elect to take
supplementary testosterone both
for sexual and general energy
enhancement.
A prudent goal of
supplemental testosterone
therapy is the concept of
keeping blood levels
within a physiological
range
Of all available supplemental
testosterone preparations,
methyltestosterone alone doesn’t
readily aromatize to estradiol;
therefore, this may be the preferred
supplement for women for whom it
seems prudent to keep estrogen
levels as low as possible.
Testosterone Supplementation
Dozens of articles have been
published in the medical archives
documenting and attesting to the
effectiveness of testosterone
supplemental therapy in restoring
sexual libido and in relieving the
other symptoms of testosterone
deficiency in women.
Symptoms of testosterone
deficiency are not clinically subtle;
however, some women are
uncomfortable about initiating
discussions about their problems.
The most help physician is one who
inquires about changes in sexual
libido, energy, sense of well-being,
and who helps a woman evaluate
her particular risk/benefit factors
among the options available for
treatment.
Recognizing the cardioprotective,
bone saving, and other benefits of
adequate estrogen supplementation,
a decision about the risks/benefits
of estrogen (with adequate
progestion for women with an
intact uterus) as a foundation for
subsequent testosterone
supplementation makes good
clinical sense. If a woman has
already been using estrogen – and,
if indicated, adequate progestin –
testosterone supplement can be
added to her established hormonal
regimen.
A prudent goal for supplemental
testosterone therapy is the concept
of keeping blood levels within a
physiological range. Clinical
experience has shown the effective
range of oral dosage to be .25 mg to
.8 mg of methyltestosterone per
day, with most women benefiting
from .3 mg to .6 mg. Prescriptions
for flexible, low enough dosing of
oral methyltestosterone must he
compounded to order.
Methyltestosterone and Liver
Function
Warnings about the potential
hepatotoxicity of oral
methyltestosterone have been
based on case reports in which
the daily oral dosage ranged
from 20 mg to 150 mg – dosages
hugely in excess of any
recommended as supplemental
for women. A recent two-year
study of women receiving 2.5
mg of oral methyltestosterone
(three to ten times the
recommended dose range of .25
mg to .8 mg) revealed no
clinically significant changes in
liver function tests. For women
taking the recommended dose of
supplemental
methyltestosterone, a
thoroughly prudent course
would be to monitor liver
function annually.
To Avoid Virilizing Side
Effects
The possibility of undesirable
side effects is naturally a major
concern of women deciding
about supplemental
testosterone. Testosterone
supplementation within the
physiological range (.25 mg to .8
mg per day) does not produce
Virilizing side effects. Only
excessive, long-term dosage may
result in the development of
Virilizing side effects – acne,
increased downy facial hair, and
(in extreme cases) lowered
voice.
I have discovered that there is a
sensitive” window” of dosage
that works best for a particular
woman at a particular time.
This dose may change – as may
the dose of estrogen supplement
functions continue to diminish
over the decade following
menopause. If a woman takes
more testosterone than needed,
she will not experience stronger
stimulation of libido, but will
more likely experience
irritability – a signal to reduce
the dose.
Topical Testosterone
Because testosterone deficiency
can result in genital atrophy
(even for women who have been
using supplementary estrogen),
women who begin
supplementing with oral
methyltestosterone may
sometimes receive benefits to
energy and sense of well being
without significant improvement
in genital sensation and libido. I
have discovered that testosterone
deficient women sometimes
require a once/daily application
to the genital mucosa of a small
amount of topical testosterone
(1%-2%) for an initial few
weeks. When the tissue
becomes healthy and local
testosterone receptors have been
well supplied, sensation and
libido return.
Topical testosterone is very
well absorbed by healthy genital
tissue and can potentially result
in high blood levels – above the
physiological range.
Intermittent monitoring of
testosterone levels will allow for
modification of concentration or
dose schedule. Once libido has
improved and capacity for
genital stimulation has been
established, a shift to an oral
supplement will usually maintain
an adequate effect on the
genitals.
Another caution against longterm daily use of topical
testosterone on the genital
mucosa is the potential for local
overstimulation and gradual
clitoral enlargement – both
reversible on discontinuation of
topical testosterone. Should this
ensue, a change to physiological
oral dosage is advisable and
effective.
Testosterone supplementation
within the physiological range
(.25 mg to .8 mg per day) does
not produce Virilizing side
effects
Testosterone and
Cardiovascular Risk
Factors predicting increased
cardiovascular risk in
menopausal women (those not
receiving supplemental estrogen
or testosterone) include:
 Increased serum levels
of cholesterol,
 Decreased high-density
lipoprotein (HDL)
cholesterol, and
 Increased low-density
lipoprotein (LGL)
cholesterol.
Estrogen therapy counteracts
some changes by:
 Increasing HDL
cholesterol, and
 Decreasing total and
LDL cholesterol.
However, only 25%-50% of the
cardioprotective effects of
estrogen are attributable to its
effects on the lipid profile; 50%75% of the benefits of estrogen
are due to effects on coagulation
parameters, vasodilatation, and
carbohydrate metabolism.
Adding testosterone to
estrogen supplemental therapy
has been shown to:
 Reduce total cholesterol
 Reduce LDL
cholesterol,
 Reduce triglycerides,
and also
 Reduce HDL
cholesterol.
The three year Postmenopausal
Estrogen and Progestin
Intervention ural micronized
progesterone in an oil suspension
did not interfere with the
beneficial effects of estrogen on
HDL cholesterol levels, as
compared with the effects of the
use of synthetic progestins. As
with formulations for
testosterone supplements,
formulations of natural
micronized progesterone in oil
are available only by prescription
compounded to order by one of
the 1, 500 compounding
pharmacies in the U.S.
Depending upon patient
history for cardiovascular risk
factors and lipid profile changes
with aging, it appears prudent to
monitor serum lipids for women
who need and choose to take
supplementary testosterone, and
to emphasize the need for
reasonable diet and healthy
exercise.
Focus for Further Research
For more definitive answers to
cardiac and cancer risk/benefits,
testosterone supplemental
therapy must be included in
longer-term research protocols.
Shorter- term studies to confirm
lowest effective dosage range,
comparative effects of routes of
delivery, and epidemiologic data
are also pressing for attention.
As a recent review of the role
of androgens in women’s health
concluded: “Future research
should be aimed at identifying
those women who have not
undergone surgical or medical
castration but have decreased
functional androgenic activity…
Androgen replacement therapy
is a neglected area of medical
practice and further research is
needed to identify all women
who will benefit from it”
Susan Rako, MD, is a Boston
psychiatrist in private
practice and a consultant
and lecturer on the subject
of testosterone deficiency
and supplementation for
women. She is also the
author of The Hormone of
Desire: The Truth About
Menopause, Sexuality, and
Testosterone.
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