Casson_edit.qxp 8/8/08 12:36 Page 82
Menopause
high risk of delivering supraphysiological doses with consequent virilization were observed, as well as clear adverse effects on lipid profiles,
androgeniziation. Further studies demonstrating the safety of gel and the long-term side effects of this medication have yet to be
preparations in women are still necessary, but this remains a promising determined.
24
The 2006 Endocrine Society General Practice Guideline
option for the future. DHEA, an indirect way to deliver T through recommends against making a diagnosis of androgen deficiency. They state
endogenous bioconversion, is available in oral, vaginal, and transdermal that although there is evidence for the short-term efficacy of T in selected
forms. Again, adverse lipid profiles and variable response to therapy limit populations, such as surgically menopausal women, they recommend
its use, but it may be a reasonable alternative to consider in refractory against the generalized use of T by women because the indications are
cases, especially when endogenous serum DHEA appears low. inadequate and evidence of safety in long-term studies is lacking.
25
As previously mentioned, evidence from controlled trials supports the Concluding Remarks
efficacy of a 300µg/day T patch (Intrinsa
®
) for women who are already It is clear that post-menopausal androgen replacement therapy is increasing
receiving estrogen therapy and who develop hypoactive sexual desire despite the lack of clear guidelines regarding the diagnosis of androgen
after bilateral salpingo-oophorectomy.
23
These studies were designed to insufficiency. There are likely multiple beneficial effects of physiological T in
last only 24 months and the consequences of long-term use remain women, but the data are not level 1-A. Regulatory and expert panels in the
unknown.
19,21
With this concern in mind, in 2004 the US Food and Drug US have stopped short of recommending androgen replacement therapy,
Administration (FDA) elected not to approve the Intrinsa T patch based and the North American Menopause Society (NAMS) advises using T only in
on inadequate long-term safety data. T patches, including Intrinsa, are post-menopausal women to enhance sex drive at the lowest dose for the
currently available outside the US. If the preliminary data hold, the shortest time necessary. Hypoactive sexual desire is a complex problem and
female T patch may ultimately prove to be the best delivery system. involves multiple factors such as the patient’s health, her relationship with
Additional studies are currently under way to assess long-term safety. and availability of a partner, the use of other concurrent medications, and
psychosocial factors.
In the US, no androgen replacement therapy has been approved for
treating hypoactive sexual desire. Oral MT (1.25–2.5mg) combined with After ruling out confounding medical conditions, the current data suggest
0.625mg esterified estrogen remains the only androgen preparation that is that a short trial of low-dose androgens is generally safe and may be
FDA-approved for women for the treatment of moderate to severe efficacious for some women concurrently receiving estrogen therapy. T
vasomotor symptoms, atrophic vaginitis, and vulvar atrophy associated replacement in women, although imperfect, clearly improves sexual
with menopause. When added to estrogen replacement therapy, MT function, probably improves bone mineral density over estrogen alone,
appears to improve fatigue, libido, and bone mineral density while increases lean body mass, and may improve strength when given in
decreasing the frequency of hot flashes. physiological doses.
23
Data on the T patch have been promising, and this
may ultimately prove to be the best delivery system once the long-term
Much higher doses of MT (used in men) have been demonstrated to cause safety analysis is available. Until then, off-label use of these products will
hepatic dysfunction and adverse lipid profiles, and possibly induce likely continue but should be met with caution. Thorough patient
hepatocellular carcinoma. However, initial studies using low doses in counseling, the evaluation of T levels, and the monitoring of hepatic
women show no hepatic complications, but several mild cases of function (including lipids) are critical. ■
1. Burger HG, Dudley EC, Cui J, et al., A prospective longitudinal 2000;85:645–51. prevalence and predictors, JAMA, 1999;281:537–44.
study of serum testosterone, dehydroepiandrosterone sulfate, and 9. Arlt W, Callies F, Christoph van Vlijmen J, et al., 18. Dennerstein L, Dudley E, Burger H, Are changes in sexual
sex-hormone binding globulin levels through the menopause Dehydroepiandrosterone replacement in women with adrenal functioning during midlife due to aging or menopause?,
transition, J Clin Endocrinol Metab, 2000;85:2832–8. insufficiency, N Engl J Med, 1999;341:1013–20. Fertil Steril, 2001;76:456–60.
2. Davis SR, Androgen treatment in women, Med J Aust, 10. Wilson CM, McPhaul MJ, A and B forms of the androgen receptor 19. Buster JE, Kingsberg SA, Aguirre O, et al., Testosterone patch for
1999;170:545–9. are expressed in a variety of human tissues, Mol Cell Endocrinol, low sexual desire in surgically menopausal women: a randomized
3. Burger NZ, Casson PR, The pathobiology of androgens in women. 1996;120:51–7. trial, Obstet Gynecol, 2005;105:944–52.
In: Nieschalg E, Hermann BM (eds), Testosterone: Action, 11. Buster JE, Aging, androgens, and female sexual desire: can we 20. Braunstein GD, Sundwall DA, Katz M, et al., Safety and efficacy of
Deficiency, Substitution, 3rd edition, Cambridge University Press, restore what time takes away?, Sex, Reprod, Menopause, a testosterone patch for the treatment of hypoactive sexual desire
2004:543–69. 2005;3(1):3–7 disorder in surgically menopausal women: a randomized,
4. Meldurm DR, Davidson BJ, Tataryn IV, Judd HL, Changes in 12. Davis SR, McCloud P, Strauss BJG, Burger HG, Testosterone placebo-controlled trial, Arch Intern Med, 2005;165:1582–9.
circulating steroids in post-menopausal women, Obstet Gynecol, enhances estradiol’s effects on postmenopausal bone density and 21. Simon J, Braunstein G, Nachtigall L, et al., Testosterone patch
1981;57:624–8. sexuality, Maturitas, 1995;21:227–36. increases sexual activity and desire in surgically menopausal
5. Casson PR, Elkind-Hirsch KE, Buster JE, et al., Effect of post- 13. Ho MH, Bhatia NN, Bhasin S, Anabolic effects of androgens on women with hypoactive sexual desire disorder, J Clin Endocrinol
menopausal estrogen replacement on circulating androgens, muscles of female pelvic floor and lower urinary tract, Curr Opin Metab, 2005;90:5226–33.
Obstet Gynecol, 1997;90:995–8. Obst Gynecol, 2004;16(5):405–9. 22. Davis SR, Davison SL, Donath S, Bell RJ, Circulating androgen
6. Thorneycroft IH, Stanczyk FZ, Bradshaw KD, et al., Effect of 14. Kritz-Silverman D, Barrett-Connor E, Wingard DL, Hysterectomy, levels and self-reported sexual function in women, JAMA,
low-dose oral contraceptives on androgen markers and acne, oophorectomy, and heart disease risk factors in older women, 2005;294:91–6.
Contraception, 1999;60:255–62. Am J Pub Health, 1997;57:678–80. 23. Somboonpron W, Androgen and menopause, Curr Opin Obstet
7. Siddle N, Sarrel P, Whitehead M, The effect of hysterectomy on the 15. Miller KK, Biller BMK, Schaub A, et al., Effects of Testosterone Gynecol, 2006;18(4):427–32.
age of ovarian failure: identification of a subgroup of women with Therapy on Cardiovascular Risk Markers in Androgen-Deficient 24. Simon JA, Safety of estrogen/androgen regimens, J Reprod Med,
premature loss of ovarian function and literature review, Fertil Women with Hypopituitarism, J Clin Endocrinol Metab, 2001;46:281–90.
Steril, 1987;47:94–100. 2007;92(7):2474–9. 25. Wierman ME, Basson R, Davis SR, et al, Androgen Therapy in
8. Laughlin GA, Barrett-Conner E, Wingard DL, Hysterectomy, 16. Burger HG, Androgen production in women, Fertil Steril, Women: An Endocrine Society Clinical Practice Guideline, J Clin
oophorectomy, and endogenous sex hormone levels in older 2002;77(4):S3–5. Endocrinol Metab, 2006;91(10).
women: the Rancho Bernado Study, J Clin Endocrinol Metab, 17. Laumann EO, Paik A, Rosen RC, Sexual dysfunction in the US:
82 US OBSTETRICS & GYNECOLOGY
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100  |  Page 101  |  Page 102  |  Page 103  |  Page 104  |  Page 105  |  Page 106  |  Page 107  |  Page 108  |  Page 109  |  Page 110  |  Page 111  |  Page 112  |  Page 113  |  Page 114  |  Page 115  |  Page 116