Chapter Sixteen

Testosterone
Deficiency and Treatment
in Women

Case Study of a Woman with Testosterone Deficiency

Michelle, with her failing sex drive, excessive emotions and eternal doubting

Michelle is an attractive young lady of 30 years. Because of her pretty, feminine body, she is
sought after by men. But Michelle has one big problem. Although she desperately needs and
seeks affection, she doesn't really feel sexually attracted to men of any type even though she is
not gay. Her libido is near zero and having sex with a man is just such a boring, tiresome
activity. She has had very few orgasms. The few times it occurred, it took such a long time and
effort to achieve it that her partner stopped trying to make her have an orgasm again.
Physically, she looks pale and has thin muscles. Sports are not her field of interest, as physical
activity tires her easily.

Emotionally, she is known for her anxiety, hesitancy and lack of assertiveness. Michelle is
rather short tempered. From time to time, she explodes in outbursts of anger or anxiety that
sometimes approach hysteria.

She has taken birth control pills from puberty onward, not for contraception, but to get rid of her
painful menstrual cramps. In her late teens as she started to have acne, she took a pill that
contained a medication that blocked androgen activity, which only seemed to have aggravated
her problems.

What is the source of Michelle's problems? Most of Michelle's problems are typical of
testosterone deficiency. To better understand the impact of this deficiency in women and what
can be done about it, let us review the basic information on testosterone.

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Testosterone in Women: Basic lnformation

Roles of Testosterone in women

Testosterone performs the following important roles in women:

1. lmprovement of mood and assertiveness, reduction of depression and anxiety.

2. lmprovement of bone density, muscle size and strength, and skin sebum secretion.
3. Enhancement of sex drive and sexual sensitivity, including orgasm.
4. Maintenance of the female genital system: nipples, labia majora (vulva lips) and in particular
the clitoris (size, sensitivity), female body hair pattern.
5. Possible protection against atherosclerosis. In two studies higher leveis of testosterone in
women (DHEA and androstenedione also) were found to be significantly associated with
thinner intima media of the carotid arteries, which lowers the risk of atherosclerosis.

Testosterone production

The daily production of testosterone in young healthy women approximates 250 micrograms, an
amount that is 20 to 30 times lower than what is produced in men. Despite the difference, it is
our experience that testosterone is nearly as important to women as it is to men.
Half of the testosterone in women comes from the conversion of DHEA and androstenedione in
fat and skin tissues, one-fourth is made by the ovaries and one-fourth by the adrenals. The
pituitary hormone LH is the hormone that stimulates testosterone production from the ovaries;
the pituitary ACTH stimulates testosterone production by the adrenals.

Progressiva decline of Testosterone leveis with age

The decrease occurs earlier and initially at a greater rate for women than for men. A study
reported that the average testosterone blood levei in women of age 40 is low, less than half of
that in women of 21 years of age.

What factors can influence Testosterone production?

Intensa physical activity such as long-distance running and other vigorous sports make the
body consume high amounts of testosterone, thereby depleting androgen leveis. Moreover,
intensa emotional stress inhibits the release of LH, and thus testosterone secretion. Foods high
in protein or saturated fat increase testosterone production. On the other hand, many foods
can reduce leveis of testosterone and of DHEA, the main provider of testosterone in women.
Sugar and sweets do this by decreasing androgen production. Cereais rich in fiber (whole grain
bread, bran flakes) reduce testosterone by increasing the loss of testosterone in the stools
(much of the testosterone is secreted in the bile and thereafter reabsorbed in the gut and used
again, cereal fiber sticks to the testosterone and inhibits its enterohepatic cycle).

Principal metabolites of Testosterone:

Dihydrotestosterone and particularly androstanediol glucuronide. Dihydrotestosterone (DHT) is

the main metabolite of testosterone and its androgen potency is three times greater. After
having expressed its activity, DHT converts into the metabolite androstanediol glucuronide.
Measuring the leveis of this major androgen metabolite best reflects male hormone metabolic
activity.

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 I. Female Testosterone Deficiency:
DIAGNOSIS

How do you detect testosterone deficiency in women?

Testosterone deficiency is best detected with physical examination, medicai history, complaints
and laboratory tests.

1. Onset of Female Testosterone Deficiency

When did the testosterone deficiency start? Women with (untreated) testosterone deficiency,
which started at puberty, show signs of sexual immaturity. The most characteristic sign of it is a
lack of body hair. The basic differences between puberty- and adult-onset testosterone
deficiencies are summarized in the following table. The patient should be asked if any of the
signs and symptoms listed below have been present since puberty to determine the onset.

Determining the Onset of Testosterone Deficiency in Women

Onset Puberty Adulthood
• Horizontal hair line (no hair recession • Hair recession at sides of the
Hair
at sides of the forehead) forehead
Face • Smooth, thin childlike face • Female face, but older looking
Voice • Higher, childish voice • Mature female (adult) voice
• Larger, better developed,
Muscles • Thin, poorly developed muscles
• but atrophying muscles
• Dry skin (absent sebum) with little to
Skin • Normal skin and body scent
no body scent
Body • Normal female pattern of body hair,
• Little to no body hair
h air but thinning
• The pubic is normal (has grown up to
Pubic • The pubic hair is limited to a small
the upper horizontal border of the
h air zone around the vulva
pubis in a inverse pyramid shape)
Clitoris • Smaller clitoris • Normal-sized clitoris
Libido • Underdeveloped sex drive • Developed sex drive but reduced
Clitoris • Underdeveloped sexual sensitivity • Developed but reduced sensitivity
• lnfrequent or absent orgasms • Able to achieve orgasm, but
Orgasm
(frigidity) increasingly difficult
• Submissive, lacks authority • Normal behavior and attitudes but
• Rigid becoming more passive since the
Behavior • Often lacking initiative onset of the deficiency
• Anxious; little self-assurance • Likes physical activity and sports, but
• Avoids sport and physical activity the interest has been fading recently
• Presents the above mentioned
Medicai • Problems started much later in
mental, physical and sexless
history adulthood
characteristics since puberty

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2. Timing and Location
When and where do testosterone deficiency signs and complaints occur?

When? Typically, testosterone deficiency signs and symptoms are chronic throughout the day.
They increase with physical activity such as sports that put strain on the muscles.
Where? The parts of the body most affected by testosterone deficiency are the brain,
muscles, bones and areas related to sexual maturity.

3. Complaints of Testosterone Deficiency in Women

What do women with testosterone deficiency complain about?

The main complaints of testosterone deficiency a female patient may express are summarized
in the following table.

COMPLAINTS of Testosterone Deficiency in Women

MENTAL
• Nervous
• Depression the whole day long
Behavior • lrritable Mood
• Excessiva anxiety, fears
• 111 at ease
• Lack of mental firmness
• Excessiva emotions
• Undecided, hesitating
• Excessiva sensitivity to
• Lack of self confidence,
Character difficulties, low resistance to
lack of assertiveness Stress
stress
• Lack of authority,
• Unnecessary worry
submissiveness
• Hysterical reactions
Memory • Poor memory
PHYSICAL
• Hypochondriac (frequent • Reduced muscle strength,
Health Muscles
complaints of being sick) volume, (rare) muscle pains
• Aging appearance • Back pain up to lumbago and
Physical Bones
• Abdominal obesity sciatica
appearance
• Muscle laxity Joints • Jointpain
• Hot flushes • Dry skin
• Day and night sweat Skin • Easily sun-burned skin
Temperature
outbursts (especially (Caucasian women)
head and upper chest) Bladder • Urinary incontinence
• Permanent fatigue that Decreased or absent:
Energy/ increases with physical • libido
Sex
vitality activity • clitoris and nipple sensitivity
• Low energy, tires easily • orgasm
Exercise
• Vaginal pruritus (itching)
Sports • Lack of interest Vagina
• Painful intercourse
• Lack of endurance

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4. Physical Signs of Testosterone Deficiency (Women)
The principal physical signs of testosterone deficiency that can be seen at physical examination
of a female patient are summarized in the following table.

PHYSICAL SIGNS of Testosterone Deficiency in Women

• Pai e • Nervous
• Slumped, fragile • lrritable
Behavior
Physical • Older looking (adulthood-onset • Hesitant
appearance deficiency); younger looking
(uncorrected early puberty-onset • Depressiva,
Mood
deficiency) • Neqative attitude
Back • Kyphosis, lordosis Mental • Poor concentration
• Often overweight, even obese Memory • Poor memory
Fat • Fat accumulation on the breasts, • Higher, more anxious
abdomen and hips Voice
tone
• Lack of body hair:
o Loss of height (adulthood-onset • Puberty type: small
deficiency); patches of dense body
Body
Height • Sometimes taller than average hair
hair
(some forms of uncorrected early • Adult type: less dense
puberty-onset deficiency) but larger patches of
bodv hair
• Pale face
• Poorly muscled (hypotonic) face • Pale skin
Face • Small wrinkles at the corner of Skin • Atrophic skin, dry, thin
eyes • Bruises easily
• Small vertical wrinkles above lios
Eyes • Dry eyes • Lack of sexual body
Scent
Armpits/Pubis • Decreased armoit and oubic hair scent
Arms, back, • Poor or reduced muscle
• Poor muscle volume Muscle
belly, legs volume, tone, strength
• Flabby belly
Abdomen Clitoris • Smaller clitoris
• lncreased abdominal fat
Thighs • Cellulite • Vaginal atrophy,
Vagina
Leas • Varicose veins dryness, pruritus

5. Disease Susceptibility
Which diseases develop easier in patients with testosterone deficiency?

Based on the known effects of androgens, it is likely that long-term testosterone deficiency
predisposes women to depression, anxiety disorders, joint disorders (osteoarthritis, rheumatoid
arthritis), osteoporosis and atherosclerosis.

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6. Lab Tests for Testosterone in Women

Which lab tests help to confirm the diagnosis of testosterone deficiency in women?

The best tests to evaluate daily testosterone production in blood is total testosterone and also
DHEA sulfate, as in women more than 90% of the testosterone comes from DHEA. But
knowing the production is not sufficient, for we also need to know how much of the testosterone
that is produced is available to the target cells? The best tests to evaluate the availability of
testosterone to the target cells are free testosterone and the ratio total testosterone/SHBG
(the higher the ratio, the greater the androgen effects). Even more important is to know how
much of the testosterone is effectively used to exert androgen action after being converted into
dihydrotestosterone? The best marker to measure this androgen metabolic activity is obtained
by measuring in the blood the major metabolite androstanediol glucuronide. 24-hour urinary
testosterone 1s both a good marker for testosterone production and availability.

BLOOD Lab Tests (at 8 a.m.) for Testosterone in Women

Opti- P. Defi- References3 Test
TEST lnformation
mal1 cienf (young adults) �alue4
LH 3 � 8 2-12 miU/mL Low lncreases T production
35 0-25 10-50 ng/ml
Total testosterone Serum total T is more stable in
350 0-250 100-500 pg/ml Med3
(T) blood than serum free T
1.2 0-0.9 0.3-1. 7 nmoi/L
8 0-5 2-15 pÇJ/ml
Free testosterone* Low Fluctuates
28 0-17 7-52 pmoi/L
30-120 pg/ml Low E2 may be a sign of low T
90 0-60 Low
(follicular phase) (the precursor of E2), or of excess
4
Estradiol (E2) '5 T (because of the progestative
0-120 100-250 pg/ml
150 Med activity of T); Hiqh E2 leveis may
or>220 (luteal phase) reduce testosterone effects
Less valuable than androstanediol
250 0-180 80-350 pg/ml
(as DHT does not reflect
Dihydro-
Med androgen activity and the test kit
testosterone (DHT)
860 0-619 275-1204 pmoi/L quality is poor), 10x lower levei
than T
Androstanediol 3-3.9 0-2 0.1-6.0 nÇJ/mL Major DHT metabolite ; reflects
High
glucuronide (AG) 10-23 0-7 0.3-20 nmoi/L androgen metabolic activity
0-5.2 A hiqh SHBG excessively binds
6.1 3.9-7.7 mg/L
SHBG or � 8.5 androgens in the blood, reducing
Med
(TeBG) 0-55 or the uptake of T by target cells,
65 41-79 pmoi/L
� 90 thus reducing its cellular effects
280 0-200 80 - 480 IJÇJ/dl
Main substrate for the
DHEA sulfate 2800 0-2000 800-4800 ng/ml Med
production of T in women
9. 7 0-6.9 2.8-16.6 J1moi/L
Androstenedione 2.5 0-2.0 1.0 -3.5 nglml) Low Substrate for T production

Notes: Symbol'�" means more or equal to; "p. deficienf' means "probably deficient"
1
The optimal value is presented for a woman with a height of 5'4 and 125 pounds (1 meter 70 and 55-60
kg). Ta/ler women with an athletic build may need higher optimal testosterone leveis; whereas in shorter
women with minimal muscle development lower leveis may suffice; 2 Ranges of deficient values in
testosterone and related hormones; 3 References of adult women age 20-30 years;
4 Test value: estimated usefulness for use in practice.

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