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Male
Hormones (Androgens) and Female Sexuality --
A Look at Pharmacology
Female sexuality
is much more complicated than male sexuality with multiple factors
concerning desire, including such disparate items as level of
education, past sexual experiences, sexual expectations, cultural
and religious beliefs, availability of a partner and of course,
the individual’s hormonal status.
Many hormones
may influence female sexuality, including estrogens (female
hormones), oxytocin, progesterone, androgens and all their metabolites.
Estrogen deficiency is most commonly seen in the peri-menopausal
and postmenopausal women and include vasomotor symptoms including
hot flashes, night sweets, urogenital atrophy and often a diminution
in sexual desire.
In addition,
there is frequently a decrease in a feeling of well being, atrophy
of the vagina, anxiety, emotional instability, depression, decline
in short term memory and concentration, myalgia, arthralgia,
an aversion to be touched and in general these also can lead
to a decrease in sexual desire. Estrogen replacement will alleviate
most of these vasomotor symptoms, including vaginal atrophy,
but desire and restoration of female libido may not always occur
in the estrogen treated peri-menopausal and postmenopausal women.
This has
lead to the theory that in postmenopausal women where desire
is not elevated by estrogen replacement there may be an androgen
deficiency. On the other hand, if we are to treat women with
androgens in a safe and effective manner, doctors must weigh
the risks.
The ability
of laboratory techniques to define hypoandrogenism in women
is hampered by the inability of the laboratory test themselves
to measure testosterone levels of the lower end of the normal
female reproductive range.
On the other hand, there is an entity in postmenopausal women
treated adequately with estrogen therapy that not only includes
low sexual libidos but decrease sexual motivation, fatigue,
lack of well being and probability low levels of bioavailable
free testosterone.
Before a
doctor treats women with androgen replacement therapy adequate
estrogen therapy must be instituted and consideration for mental
health counseling or referral to a sex therapist should be made.
This androgen deficiency syndrome, however, is accepted for
women who have had bilateral ovariectomy or in younger women
who have suffered primary or secondary ovarian failure associated
with low libido and low blood androgen levels.
What causes
low levels of male hormones in women. The ovaries produce androstenedione,
testosterone and dehydroepiandrosterone (DHEA). The adrenals
produce androstenedione and dehydroepiandrosterone sulfate (DHEA-S).
The DHEA-S can be further metabolized to testosterone or estrogens.
In addition the testosterone through the enzyme of 5-alpha reductants
converts the serum testosterone to dihydrotestosterone (DHT)
or estradiol (E2) these are the active hormones that work within
the cells.
Age in general
leads to a drop in androgen levels in women and is due to the
age-related drop in adrenal production of androgen and the loss
of the mid-cycle surge in ovarian testosterone. Removal of the
ovaries results in a reduction of 50 percent in testosterone
and androstenedione. Chemical oophorectomy including chemotherapy,
use of GNRH hormone inhibitors, radiation therapy, glucocorticoids
and the administration of exogenous estrogens are other causes
for diminution in androgens. Oral postmenopausal estrogen therapy
and oral contraceptives will suppress free testosterone by increasing
serum hormone binding globulins (SHBG) and suppressing pituitary
luteinizing hormone (LH).
Steroids
by mouth suppress pituitary secretions of adrenal corticotropic
hormone and therefore adrenal androgen production as well. This
probably explains the bone loss frequency in patients who are
taking long-term steroids. Lastly, hypothalamic amenorrhea and
hypoproaccelerinemia are usually associated with low testosterone
and many women with premature ovarian failure have low testosterone
levels. Therefore, the use of oral contraceptives in older women
or women with amenorrhea or premature ovarian failure may actually
worsen their androgen deficiency.
How testosterone
therapy affects female sexuality is not well understood although
it is a clinically known factor. The male hormones may work
directly on androgen receptors or may be a precursor for additional
estrogen production in tissue such as fat, bone, brain, blood
vessels or possibly by lowering serum hormone binding globulins
(SHBG) and therefore causing an increase in the levels of bioactive
steroids such as androgen. Probably the mechanism is all of
the above.
There is
no doubt that the administration of testosterone to older women
with sexual desire problems improves the intensity of sexual
desire, arousal, frequency of sexual fantasies, satisfaction,
pleasure and relevancy and importance of sex to daily life.
And therefore, postmenopausal women who are probably treated
with estrogen therapy should be offered androgen replacement
to improve this symptom complex.
A more difficult
question deals with the pre-menopausal women who complains of
decreased sexual drive and libido and who have low bioavailable
testosterone. Studies have not been done; each case should be
individualized especially in those individuals in which other
factors do not appear to play a role in desire and where the
psychosocial and sexual history indicates hormonal problem as
being the basic ideology of their libido decrease.
The administration
of testosterone has been formulated and fairly much determined
for men but androgen replacement therapy in women has no true
guidelines and in the United States there are no drug indications
for the use of androgens in women. Oral methylated testosterone
is available in the United States and should be administered
in combination with esterified estrogens (E.E.) 1.25 milligrams
of methyltestosterone with 0.625 milligrams of E.E. or 2.5 milligrams
of methyltestosterone with 1.25 milligrams of E.E. Patients
obviously have to be warned about androgen side affects including
increase in high density lipoproteins, cholesterol and low density
lipoproteins, adverse liver affects including chemical hepatitis
and possibly a higher incidence of liver cancer. More commonly,
however, testosterone will lead to masculinizing tendencies
which should be monitored by the patient and her physician should
be informed if such occurs.
Oral testosterone
undecenoate has not been studied in women and doses as low as
20 milligrams appear to cause undesirable side effects and therefore
is not recommended at this time.
Subcutaneous
implants of testosterone is not available in the United States
at this time, but has been in Australia and the United Kingdom
for many years and has found to be quite effective for up to
six months. Doses of 50 to 100 milligrams appeared to affectively
raise the levels of testosterone for up to six months to adequate
levels to treat sexual desire problems. In the United States
compounding pharmacists are able to manufacture a subcutaneous
testosterone pellet which could easily be implanted by your
physician.
Injectable
depo-testosterone in the form of testosterone esters appears
to be the safest and most commonly tried form of androgen replacement
in women in the United States. The most common administration
is 50 to 100 milligrams administered every four to six weeks
intramuscular. However, many physicians use 20 milligrams every
three weeks. Masculinization with increased acne and occasional
clitoral myoglia may occur with this therapy.
Recently
transdermotestosterone patches have been manufactured and approved
for use by men and newer technology is developing androgen replacement
patches for women. Patches that increase testosterone levels
greater than 25 nanograms per DL appear to produce significant
masculinization and side affects that they should not be used.
Transdermotesosterone
as a cream or a jell or testosterone using a transvaginal testosterone
impregnated cream is available in the United States by specific
prescriptions or through compounding pharmacists.
Contraindications
to testosterone treatment include: acne, hirsutism, alopecia,
and circumstances in which enhancing libido would be undesirable.
Absolute contraindications include pregnancy and lactation as
well as known or suspected androgen dependent neoplasia. Side
effects from excessive testosterone include virilization, fluid
retention and an adverse lipoprotein profile which more likely
occur with the oral administration of the drug. Afenteral administration
raising levels of testosterone to within physiologic ranges
does not appear to have any undesirable metabolic effects. It
is not known whether additional androgen will affect breast
cancer since more than 50 percent of breast cancers have androgen
receptors and these are associated with a longer survival in
women.
In conclusion,
androgen deficiency in women causing various symptoms including
poor sexual desire is an entity that exists both in the menopausal
and probably pre-menopausal female. In the peri or postmenopausal
female the patient should be adequately treated with estrogen
therapy before using androgen replacement. And the pre-menopausal
woman who appears to have low bioactive levels of testosterone,
androgen replacement should be used with closer monitoring.
by
Myron I. Murdock, M.D., FACS
Medical Director, hisandhershealth.com
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