Androgens in Health and Disease.pdf - E Library

368 Davis
transdermal testosterone compared with placebo (author’s unpublished data) in a 12-wk
double-blind crossover trial.
Dedydroepiandrosterone given orally (50 mg/d) (23) or transdermally (by a 10%
DHEA cream) (24) is associated with a marked improvement in well-being over placebo.
Oral DHEA improves well-being and depression and anxiety scores in women with
adrenal insufficiency (25). However, not all DHEA trials have been positive (26,27).
Larger prospective trials with this steroid are required before definitive guidelines can
be developed for its clinical use.
LOW TESTOSTERONE IS ASSOCIATED
WITH DIMINISHED LIBIDO IN WOMEN
Androgens also play a major role, particularly in stimulating sexual motivation
behaviors, maintaining optimal levels of sexual desire, and possibly contributing to
sexual gratification (28–30). Acute decline in sexual interest at the time of natural
menopause appears unrelated to testosterone levels (31), consistent with testosterone
levels not falling acutely at this time. Sexual dysfunction, primarily low libido, tends
to be more prevalent in women as they age or following oophorectomy (32). There is
an age-related reduction in sexual frequency among women and lessening of coital
frequency associated with the menopausal transition independent of age (33). Testosterone
is inversely correlated with reduced coital frequency and loss of sexual desire
(34,35). Antiandrogens have adverse effects on female sexual function (36), and among
lactating women, testosterone and A levels are lowest in those reporting the greatest
reduction in sexual interest (37).
It is generally accepted that estrogen replacement improves vasomotor symptoms,
vaginal atrophy, and general well-being, but may not restore libido (32,33,38). Postmenopausal
women treated with intramuscular estradiol and testosterone have improvements in
sexual motivational behaviors (desire, fantasy, and arousal) and increased frequencies of
coitus and orgasm (29), with the improvements in these sexual parameters covarying with
plasma testosterone, not estradiol (29). The effects of esterified estrogens (EE) alone vs EE
plus methyltestosterone (ET) in postmenopausal women described as being “dissatisfied”
with their hormone-replacement therapy (HRT) regimens have been reported. SHBG
increased in the EE group and decreased in the ET group. Those taking ET had significant
improvements in sexual desire, satisfaction, and coital frequency, whereas those treated
with EE alone had no improvement (39). Subcutaneous testosterone implants significantly
improve sexual activity, satisfaction, pleasure, and orgasm over and above the effect
achieved with estrogen alone (40–43). Moreover, there are no adverse effects on blood
lipids with parenteral therapy and no virilization effects.
Acute sublingual testosterone therapy results in an increase in vaginal pulse amplitude
peaking at about 4 h post-administration in association with increased subjective
sexual excitement and lust scores in young women (44). The findings of Laan and Van
Luunsen (45) indicate that complaints of vaginal dryness and dyspareunia should not be
attributed to vaginal atrophy because of estrogen deficiency but rather reflect inadequate
sexual arousal. Leiblum et al. have shown that women with a lower vaginal atrophy index
have higher androgen levels (46). Taken together with the favorable effects of testosterone
on vascular function (47), testosterone appears to be important for both central
sexual arousal and the vaginal responses of vasocongestion and lubrication.