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Q Does testosterone have a role in treating decreased sexual desire in postmenopausal women?
NAMS position statement on exogenous testosterone
The experts charged with formulating the statement noted that, while endogenous testosterone levels have not been clearly linked to sexual function in postmenopausal women, exogenous testosterone—regardless of route of administration—positively affects sexual function after spontaneous or surgically induced menopause, according to randomized controlled trials. The panel agreed on these points:
Existing data do not support using testosterone for any other indication. Nor known whether testosterone treatment raises the risk of breast cancer, cardiovascular disease, or thromboembolic events. The optimal duration of therapy beyond months is also unknown.
No level of testosterone has been clearly linked to a clinical syndrome of hypoandrogenism or testosterone insufficiency, nor do available assays accurately detect testosterone concentrations at the values typically found in women.
It is important to rule out other causes of decreased desire not related to testosterone levels, such as physical and psychosocial factors, and medications. Also recommended is ensuring a physiologic cause of reduced testosterone levels, such as bilateral oophorectomy.
Laboratory testing of testosterone levels is warranted only to monitor for supraphysiologic levels during therapy, not to diagnose testosterone insufficiency. The panel recommended non-oral testosterone to avoid first-pass hepatic effects.
Few data support the use of testosterone without concomitant estrogen therapy.
Dosing can be inconsistent in custom-compounded products, which should be used with caution.
Dosage of testosterone should be at the lowest level for the shortest time that meets treatment goals.
Expert Commentary
This position statement shows what progress can be made when you put the right people in the right room talking about a topic they know an awful lot about. The clinicians and researchers contributing to the position statement included the best and most practical in the field.
Of critical importance is the section on testosterone testing, in which utilization of testosterone blood levels (for saliva levels, that matter) to diagnose sexual dysfunction is discouraged except to avoid supraphysiologic levels during therapy. The problem here is that a total testosterone level that is supraphysiologic may be coupled with a free testosterone level within the normal range, usually due to elevated levels of sex hormone binding globulin, as is seen with oral estrogen therapy. Hence, one needs to be careful with the term “supraphysiologic” and not depend on the total testosterone level.
An empiric trial of therapy is implied if other causes are ruled out, and a “normal” blood level should not discourage therapy in affected patients.
Some women experience “double whammy”
The ovaries account, directly or indirectly, for approximately 50% of circulating testosterone even after menopause, leading to significantly decreased testosterone levels after bilateral oophorectomy. Thus, the combination of oral estrogen, with its concomitant increase in sex hormone binding globulin, and bilateral oophorectomy, with its 50% reduction in testosterone levels, becomes a “double whammy” that leads to greatly reduced bioavailable testosterone (and estrogen) and its signs of testosterone insufficiency (as well as relapse of vasomotor symptoms).
Post-Oprah counseling
The lack of FDA approval for use of any available testosterone products in women renders their utilization “off-label” in this country, which means we need to add counseling about this issue to any discussion of testosterone therapy for decreased sexual desire.
Another question that has arisen more frequently, especially since Oprah Winfrey advised her TV viewers to ask their doctors for testosterone: Should testosterone be used by a woman who wants to avoid any estrogen therapy? Women with this concern should be told that testosterone can also be aromatized to estradiol endogenously. In contrast, oral methyltestosterone is not aromatized to estradiol and, at least in vitro, has been shown to be a potential aromatase inhibitor.
Science lags behind therapy
This is a fascinating time for this area of study and therapy, but the science needs to catch up to the therapy. That will be difficult until the FDA stops its footdragging and approves a product for female use.
NAMS advisory is excellent
As for the position statement itself, NAMS has put forth an excellent treatise on the role of testosterone therapy, instead of another medicolegal-inspired statement like the one it issued after the Women’s Health Initiative, which led to more confusion and controversy.
This position statement should be read by all clinicians who manage issues of female sexual function and dysfunction. I could not have said it better myself.
NAMS position statement on exogenous testosterone
The experts charged with formulating the statement noted that, while endogenous testosterone levels have not been clearly linked to sexual function in postmenopausal women, exogenous testosterone—regardless of route of administration—positively affects sexual function after spontaneous or surgically induced menopause, according to randomized controlled trials. The panel agreed on these points:
Existing data do not support using testosterone for any other indication. Nor known whether testosterone treatment raises the risk of breast cancer, cardiovascular disease, or thromboembolic events. The optimal duration of therapy beyond months is also unknown.
No level of testosterone has been clearly linked to a clinical syndrome of hypoandrogenism or testosterone insufficiency, nor do available assays accurately detect testosterone concentrations at the values typically found in women.
It is important to rule out other causes of decreased desire not related to testosterone levels, such as physical and psychosocial factors, and medications. Also recommended is ensuring a physiologic cause of reduced testosterone levels, such as bilateral oophorectomy.
Laboratory testing of testosterone levels is warranted only to monitor for supraphysiologic levels during therapy, not to diagnose testosterone insufficiency. The panel recommended non-oral testosterone to avoid first-pass hepatic effects.
Few data support the use of testosterone without concomitant estrogen therapy.
Dosing can be inconsistent in custom-compounded products, which should be used with caution.
Dosage of testosterone should be at the lowest level for the shortest time that meets treatment goals.
Expert Commentary
This position statement shows what progress can be made when you put the right people in the right room talking about a topic they know an awful lot about. The clinicians and researchers contributing to the position statement included the best and most practical in the field.
Of critical importance is the section on testosterone testing, in which utilization of testosterone blood levels (for saliva levels, that matter) to diagnose sexual dysfunction is discouraged except to avoid supraphysiologic levels during therapy. The problem here is that a total testosterone level that is supraphysiologic may be coupled with a free testosterone level within the normal range, usually due to elevated levels of sex hormone binding globulin, as is seen with oral estrogen therapy. Hence, one needs to be careful with the term “supraphysiologic” and not depend on the total testosterone level.
An empiric trial of therapy is implied if other causes are ruled out, and a “normal” blood level should not discourage therapy in affected patients.
Some women experience “double whammy”
The ovaries account, directly or indirectly, for approximately 50% of circulating testosterone even after menopause, leading to significantly decreased testosterone levels after bilateral oophorectomy. Thus, the combination of oral estrogen, with its concomitant increase in sex hormone binding globulin, and bilateral oophorectomy, with its 50% reduction in testosterone levels, becomes a “double whammy” that leads to greatly reduced bioavailable testosterone (and estrogen) and its signs of testosterone insufficiency (as well as relapse of vasomotor symptoms).
Post-Oprah counseling
The lack of FDA approval for use of any available testosterone products in women renders their utilization “off-label” in this country, which means we need to add counseling about this issue to any discussion of testosterone therapy for decreased sexual desire.
Another question that has arisen more frequently, especially since Oprah Winfrey advised her TV viewers to ask their doctors for testosterone: Should testosterone be used by a woman who wants to avoid any estrogen therapy? Women with this concern should be told that testosterone can also be aromatized to estradiol endogenously. In contrast, oral methyltestosterone is not aromatized to estradiol and, at least in vitro, has been shown to be a potential aromatase inhibitor.
Science lags behind therapy
This is a fascinating time for this area of study and therapy, but the science needs to catch up to the therapy. That will be difficult until the FDA stops its footdragging and approves a product for female use.
NAMS advisory is excellent
As for the position statement itself, NAMS has put forth an excellent treatise on the role of testosterone therapy, instead of another medicolegal-inspired statement like the one it issued after the Women’s Health Initiative, which led to more confusion and controversy.
This position statement should be read by all clinicians who manage issues of female sexual function and dysfunction. I could not have said it better myself.
NAMS position statement on exogenous testosterone
The experts charged with formulating the statement noted that, while endogenous testosterone levels have not been clearly linked to sexual function in postmenopausal women, exogenous testosterone—regardless of route of administration—positively affects sexual function after spontaneous or surgically induced menopause, according to randomized controlled trials. The panel agreed on these points:
Existing data do not support using testosterone for any other indication. Nor known whether testosterone treatment raises the risk of breast cancer, cardiovascular disease, or thromboembolic events. The optimal duration of therapy beyond months is also unknown.
No level of testosterone has been clearly linked to a clinical syndrome of hypoandrogenism or testosterone insufficiency, nor do available assays accurately detect testosterone concentrations at the values typically found in women.
It is important to rule out other causes of decreased desire not related to testosterone levels, such as physical and psychosocial factors, and medications. Also recommended is ensuring a physiologic cause of reduced testosterone levels, such as bilateral oophorectomy.
Laboratory testing of testosterone levels is warranted only to monitor for supraphysiologic levels during therapy, not to diagnose testosterone insufficiency. The panel recommended non-oral testosterone to avoid first-pass hepatic effects.
Few data support the use of testosterone without concomitant estrogen therapy.
Dosing can be inconsistent in custom-compounded products, which should be used with caution.
Dosage of testosterone should be at the lowest level for the shortest time that meets treatment goals.
Expert Commentary
This position statement shows what progress can be made when you put the right people in the right room talking about a topic they know an awful lot about. The clinicians and researchers contributing to the position statement included the best and most practical in the field.
Of critical importance is the section on testosterone testing, in which utilization of testosterone blood levels (for saliva levels, that matter) to diagnose sexual dysfunction is discouraged except to avoid supraphysiologic levels during therapy. The problem here is that a total testosterone level that is supraphysiologic may be coupled with a free testosterone level within the normal range, usually due to elevated levels of sex hormone binding globulin, as is seen with oral estrogen therapy. Hence, one needs to be careful with the term “supraphysiologic” and not depend on the total testosterone level.
An empiric trial of therapy is implied if other causes are ruled out, and a “normal” blood level should not discourage therapy in affected patients.
Some women experience “double whammy”
The ovaries account, directly or indirectly, for approximately 50% of circulating testosterone even after menopause, leading to significantly decreased testosterone levels after bilateral oophorectomy. Thus, the combination of oral estrogen, with its concomitant increase in sex hormone binding globulin, and bilateral oophorectomy, with its 50% reduction in testosterone levels, becomes a “double whammy” that leads to greatly reduced bioavailable testosterone (and estrogen) and its signs of testosterone insufficiency (as well as relapse of vasomotor symptoms).
Post-Oprah counseling
The lack of FDA approval for use of any available testosterone products in women renders their utilization “off-label” in this country, which means we need to add counseling about this issue to any discussion of testosterone therapy for decreased sexual desire.
Another question that has arisen more frequently, especially since Oprah Winfrey advised her TV viewers to ask their doctors for testosterone: Should testosterone be used by a woman who wants to avoid any estrogen therapy? Women with this concern should be told that testosterone can also be aromatized to estradiol endogenously. In contrast, oral methyltestosterone is not aromatized to estradiol and, at least in vitro, has been shown to be a potential aromatase inhibitor.
Science lags behind therapy
This is a fascinating time for this area of study and therapy, but the science needs to catch up to the therapy. That will be difficult until the FDA stops its footdragging and approves a product for female use.
NAMS advisory is excellent
As for the position statement itself, NAMS has put forth an excellent treatise on the role of testosterone therapy, instead of another medicolegal-inspired statement like the one it issued after the Women’s Health Initiative, which led to more confusion and controversy.
This position statement should be read by all clinicians who manage issues of female sexual function and dysfunction. I could not have said it better myself.
A study with 4 inescapable limitations
Expert commentary
Four key problems limit the effectiveness of this study.
1. Inappropriate population
Seventy percent of the women in this study were between the ages of 60 and 79 with a mean age of 63. This fact disqualified the WHI’s first report as a primary prevention study of cardiovascular disease, and it has a major nullifying impact on this study as well.
Only a small percentage of older postmenopausal women have vasomotor symptoms; in this study just 12% noted them as “moderate to severe.” Women with severe vasomotor symptoms were dissuaded from joining the study due to inability to take placebo. In her editorial, D. Grady comments that, “Among the 12% of women who did report moderate-to-severe vasomotor symptoms at baseline, the symptoms were unlikely to be very bothersome, since the women were willing to be randomly assigned to placebo.”1 Hence, this is not an appropriate population from which to draw conclusions about quality of life issues.
2. Discontinuation rate was 42%
This was an intent-to-treat study and almost half of those in the study group discontinued therapy. This is certainly not unexpected when women are arbitrarily placed on a single estrogen-progestin combination therapy without regard to individualizing treatment–especially when you consider that 88% were without vasomotor symptoms at baseline. The breast tenderness, bloating, bleeding, headaches, and mood changes from a 1-size-fits-all regimen would be enough to make most women discontinue treatment if their clinicians were unable to adjust their therapy.
Subjects who stopped therapy remained in the treatment arm for determination of quality of life results. The authors admit that “it is possible that differences were not significant at 3 years because of…poorer adherence to assigned therapy.”
3. The conjugated equine estrogen/medroxyprogesterone acetate combination in this study does not represent all HRT formulations
The definition of what constitutes HRT is vastly different today than it was a mere 20 years ago. Thus, it is impossible and misleading to extrapolate the WHI results to the many different options of estrogens, progestogens and delivery systems presently available in the US.
Numerous studies have shown estrogen-associated increases in quality of life. Progestogens, especially medroxyprogesterone acetate–the most potent synthetic progestin we have–can attenuate these estrogen benefits by down-regulation of the estrogen receptor. This is a process we seek in the endometrium, but want to avoid in brain, bone, vascular tree, genitalia, and skin. Better progestogen choices now available, such as micronized progesterone, norethindrone acetate, and norgestimate, are less potent and far better tolerated in combination with the many estrogen options.
4. Quality of evaluation tools
This study attempts to evaluate quality of life using various medical scales–each designed to assess a specific function, but none developed to actually measure quality of life. The most primitive scale, utilized to evaluate “sexual satisfaction,” consisted of just 1 question with 4 choices: very unsatisfied, a little unsatisfied, somewhat satisfied, or very satisfied. Other researchers have utilized vehicles with 40 questions on a 10-point scale in studies of sexuality, and the academic sexual societies are constantly trying to evolve more sophisticated tools to evaluate this complex concept. One question simply cannot assess sexual satisfaction.
Bottom line
Individualization of therapy has been, and should continue to be, the guiding principle in helping patients decide whether or not to begin HRT, and ultimately which combination best fits their needs. This unsatisfying study uses the wrong population, continuation, combination, and evaluation and fails to consider the variations in genetic complement of estrogen receptors. No single therapy is appropriate for all women.
REFERENCE
1. Grady D. Postmenopausal hormones–therapy for symptoms only. N Engl J Med. Posted March 17, 2003. Because of its potential therapeutic implications, this article was published early at: www.nejm.org. It appears in the May 8th issue.
Expert commentary
Four key problems limit the effectiveness of this study.
1. Inappropriate population
Seventy percent of the women in this study were between the ages of 60 and 79 with a mean age of 63. This fact disqualified the WHI’s first report as a primary prevention study of cardiovascular disease, and it has a major nullifying impact on this study as well.
Only a small percentage of older postmenopausal women have vasomotor symptoms; in this study just 12% noted them as “moderate to severe.” Women with severe vasomotor symptoms were dissuaded from joining the study due to inability to take placebo. In her editorial, D. Grady comments that, “Among the 12% of women who did report moderate-to-severe vasomotor symptoms at baseline, the symptoms were unlikely to be very bothersome, since the women were willing to be randomly assigned to placebo.”1 Hence, this is not an appropriate population from which to draw conclusions about quality of life issues.
2. Discontinuation rate was 42%
This was an intent-to-treat study and almost half of those in the study group discontinued therapy. This is certainly not unexpected when women are arbitrarily placed on a single estrogen-progestin combination therapy without regard to individualizing treatment–especially when you consider that 88% were without vasomotor symptoms at baseline. The breast tenderness, bloating, bleeding, headaches, and mood changes from a 1-size-fits-all regimen would be enough to make most women discontinue treatment if their clinicians were unable to adjust their therapy.
Subjects who stopped therapy remained in the treatment arm for determination of quality of life results. The authors admit that “it is possible that differences were not significant at 3 years because of…poorer adherence to assigned therapy.”
3. The conjugated equine estrogen/medroxyprogesterone acetate combination in this study does not represent all HRT formulations
The definition of what constitutes HRT is vastly different today than it was a mere 20 years ago. Thus, it is impossible and misleading to extrapolate the WHI results to the many different options of estrogens, progestogens and delivery systems presently available in the US.
Numerous studies have shown estrogen-associated increases in quality of life. Progestogens, especially medroxyprogesterone acetate–the most potent synthetic progestin we have–can attenuate these estrogen benefits by down-regulation of the estrogen receptor. This is a process we seek in the endometrium, but want to avoid in brain, bone, vascular tree, genitalia, and skin. Better progestogen choices now available, such as micronized progesterone, norethindrone acetate, and norgestimate, are less potent and far better tolerated in combination with the many estrogen options.
4. Quality of evaluation tools
This study attempts to evaluate quality of life using various medical scales–each designed to assess a specific function, but none developed to actually measure quality of life. The most primitive scale, utilized to evaluate “sexual satisfaction,” consisted of just 1 question with 4 choices: very unsatisfied, a little unsatisfied, somewhat satisfied, or very satisfied. Other researchers have utilized vehicles with 40 questions on a 10-point scale in studies of sexuality, and the academic sexual societies are constantly trying to evolve more sophisticated tools to evaluate this complex concept. One question simply cannot assess sexual satisfaction.
Bottom line
Individualization of therapy has been, and should continue to be, the guiding principle in helping patients decide whether or not to begin HRT, and ultimately which combination best fits their needs. This unsatisfying study uses the wrong population, continuation, combination, and evaluation and fails to consider the variations in genetic complement of estrogen receptors. No single therapy is appropriate for all women.
Expert commentary
Four key problems limit the effectiveness of this study.
1. Inappropriate population
Seventy percent of the women in this study were between the ages of 60 and 79 with a mean age of 63. This fact disqualified the WHI’s first report as a primary prevention study of cardiovascular disease, and it has a major nullifying impact on this study as well.
Only a small percentage of older postmenopausal women have vasomotor symptoms; in this study just 12% noted them as “moderate to severe.” Women with severe vasomotor symptoms were dissuaded from joining the study due to inability to take placebo. In her editorial, D. Grady comments that, “Among the 12% of women who did report moderate-to-severe vasomotor symptoms at baseline, the symptoms were unlikely to be very bothersome, since the women were willing to be randomly assigned to placebo.”1 Hence, this is not an appropriate population from which to draw conclusions about quality of life issues.
2. Discontinuation rate was 42%
This was an intent-to-treat study and almost half of those in the study group discontinued therapy. This is certainly not unexpected when women are arbitrarily placed on a single estrogen-progestin combination therapy without regard to individualizing treatment–especially when you consider that 88% were without vasomotor symptoms at baseline. The breast tenderness, bloating, bleeding, headaches, and mood changes from a 1-size-fits-all regimen would be enough to make most women discontinue treatment if their clinicians were unable to adjust their therapy.
Subjects who stopped therapy remained in the treatment arm for determination of quality of life results. The authors admit that “it is possible that differences were not significant at 3 years because of…poorer adherence to assigned therapy.”
3. The conjugated equine estrogen/medroxyprogesterone acetate combination in this study does not represent all HRT formulations
The definition of what constitutes HRT is vastly different today than it was a mere 20 years ago. Thus, it is impossible and misleading to extrapolate the WHI results to the many different options of estrogens, progestogens and delivery systems presently available in the US.
Numerous studies have shown estrogen-associated increases in quality of life. Progestogens, especially medroxyprogesterone acetate–the most potent synthetic progestin we have–can attenuate these estrogen benefits by down-regulation of the estrogen receptor. This is a process we seek in the endometrium, but want to avoid in brain, bone, vascular tree, genitalia, and skin. Better progestogen choices now available, such as micronized progesterone, norethindrone acetate, and norgestimate, are less potent and far better tolerated in combination with the many estrogen options.
4. Quality of evaluation tools
This study attempts to evaluate quality of life using various medical scales–each designed to assess a specific function, but none developed to actually measure quality of life. The most primitive scale, utilized to evaluate “sexual satisfaction,” consisted of just 1 question with 4 choices: very unsatisfied, a little unsatisfied, somewhat satisfied, or very satisfied. Other researchers have utilized vehicles with 40 questions on a 10-point scale in studies of sexuality, and the academic sexual societies are constantly trying to evolve more sophisticated tools to evaluate this complex concept. One question simply cannot assess sexual satisfaction.
Bottom line
Individualization of therapy has been, and should continue to be, the guiding principle in helping patients decide whether or not to begin HRT, and ultimately which combination best fits their needs. This unsatisfying study uses the wrong population, continuation, combination, and evaluation and fails to consider the variations in genetic complement of estrogen receptors. No single therapy is appropriate for all women.
REFERENCE
1. Grady D. Postmenopausal hormones–therapy for symptoms only. N Engl J Med. Posted March 17, 2003. Because of its potential therapeutic implications, this article was published early at: www.nejm.org. It appears in the May 8th issue.
REFERENCE
1. Grady D. Postmenopausal hormones–therapy for symptoms only. N Engl J Med. Posted March 17, 2003. Because of its potential therapeutic implications, this article was published early at: www.nejm.org. It appears in the May 8th issue.