Menopause Live - IMS Updates

Date of release: 11 May, 2015

To be or not to be in sexual desire: the androgen dilemma

There is a biological plausibility for the association between sexual desire and androgens. Indeed, according to epidemiological and clinical studies, they both decline with age. However, any attempt to link directly low sexual desire with circulating low androgens (total testosterone, free testosterone) or androgen precursors (androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)) has failed to identify a lower limit that can be used to diagnose women with sexual dysfunction related to androgen deficiency [1]. A Danish cross-sectional study by Wåhlin-Jacobsen and colleagues [2] has recently reported that sexual desire, measured by the total score in the sexual desire domain of the Female Sexual Function Index (FSFI), correlated overall with free testosterone and androstenedione in a cohort of 560 healthy women aged 19–65 years. Moreover, the androstenedione : total testosterone ratio, an indirect marker of the activity of 17β-hydroxysteroid dehydrogenase, was overall correlated with women’s sexual desire in women not using systemic hormonal contraception (HC) or postmenopausal hormone therapy (HT), indicating that the speed of transformation of androstenedione to testosterone is important. When the study population was stratified into three age groups depending on the intake of HC and HT, the authors demonstrated that, in women aged 25–44 years with no use of HC, sexual desire correlated with total testosterone, free testosterone, androstenedione, and DHEAS, whereas, in women aged 45–65 years, only androstenedione correlated with sexual desire. The primary androgen metabolite androsterone glucuronide did not show a correlation with sexual desire.


The unique nature of the intrinsic and extrinsic factors influencing women’s sexuality across the lifespan limits our ability to discriminate between biological/organic components and psychological and contextual determinants of sexual response and behavior and to find effective pharmacotherapy for sexual symptoms [3]. The evidence that testosterone treatment of postmenopausal women with sexual dysfunction due to hypoactive sexual desire disorder is effective and safe in the short term [4] supports the notion that the sex steroid milieu is crucial for human sexuality and that hormonal perturbation may impact domains of sexual response. Longitudinal studies [5,6] suggested that significant changes of sexual responsivity may be observed across the menopausal transition, and both age and menopause cooperate differentially over time to decrease sexual desire and to increase vaginal dryness. However, the challenge of linking endogenous sex steroids with sexual motivation and performance capability continues to fascinate investigators who have to take into account individual variability in biosynthesis, enzymatic intracrine conversion, receptor binding, absorption rate, bioavailability, elimination, etc., when attempting to document the 'hormonal factor' by determination of circulating levels [7].
That being so, the Endocrine Society Clinical Practice Guideline confirms the recommendations against making a clinical diagnosis of androgen deficiency in women because data correlating measurements of androgens and specific signs and symptoms are inconsistent and monitoring plasma levels during testosterone treatment with available testosterone assays may be unreliable [1]. The recommendations presented at the 3rd International Consultation on Sexual Medicine [8] have already underlined the importance of using accurate methods based on mass spectrometry (MS) to measure testosterone levels at baseline or under therapy in women with sexual symptoms, but an agreed-upon standard is still lacking. The new instructions to authors for the reporting of steroid hormone measurements give hope to optimize measurement of steroid hormones in research publications in order to obtain reproducible data for standard of care [9].  
Research data obtained with MS-based methods in a large and ethnically diverse longitudinal study (SWAN) have demonstrated a modest significant association between endogenous reproductive hormones and sexual function in midlife women across the menopausal transition. Testosterone was positively associated with masturbation (the sexual function domain least dependent on partner status), desire, and arousal, whereas FSH was negatively associated with masturbation, arousal, and the ability to climax in the absence of any association with estradiol [10]. Whether such a subtle link is clinically relevant in the psycho-relational context remains to be fully established, given the evidence that, in spite of low desire, most of the women in the SWAN cohort reported to be moderately or extremely sexually satisfied [6]. It is interesting to observe that, by using both a validated questionnaire and a highly sensitive methodology (MS) to measure androgens, the Danish data [2] seem to support a stronger role of androgens in women’s sexual desire in adult women aged 25–44 years who are more likely to be in a stable sexual relationship, whereas, in younger or in older women, the role of androgen was less evident due to a stronger potential influence of other factors such as body image, self-esteem, partner status (new, absent, sexually dysfunctional), general health, co-morbidity with sexual pain disorders, etc. On the other hand, the strong associations between the pro-androgen androstenedione and the androstenedione°:°total testosterone ratio and sexual desire in women aged 45–65 years indicate that enzyme activity may play a more important role in women with lower production of androgen precursors of ovarian origin. Indeed, no statistically significant correlations were established between androsterone glucuronide and sexual desire, a finding explained by the fact that the level of androsterone glucuronide primarily represents the level of DHEAS, which reflects more the adrenal androgen reservoir. However, the cross-sectional nature of the study, the absence of a documented ovulation in premenopausal women and the lack of a significant decline of androgens with age, apart from DHEAS, are likely due to the insufficient number of postmenopausal women, and limit comments on causation.
Sexual symptoms are very common in clinical practice and health-care providers have difficulties in evaluating the wide variety of bio-psychosocial determinants that may influence the level of distress associated with low desire. It is mandatory to expand this field of research in sexual medicine, taking into account the bio-psychosocial model, which combines an optimal assessment of endocrine aspects of the sexual response in women with the intrapersonal and interpersonal clues during the lifespan, in order to establish a multidimensional, tailored treatment plan.


Rossella E. Nappi
Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause, IRCCS S. Matteo Foundation, Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, Italy


  1. Wierman ME, Arlt W, Basson R, et al. Androgen therapy in women: a reappraisal: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2014;99:3489-510

  2. WÃ¥hlin-Jacobsen S, Pedersen AT, Kristensen E, et al. Is there a correlation between androgens and sexual desire in women? J Sex Med 2015;12:358-73

  3. Nappi RE, Cucinella L. Advances in pharmacotherapy for treating female sexual dysfunction. Expert Opin Pharmacother 2015;16:875-87

  4. Davis SR, Worsley R. Androgen treatment of postmenopausal women. J Steroid Biochem Mol Biol 2014;142:107-14

  5. Dennerstein L, Dudley E, Burger H. Are changes in sexual functioning during midlife due to aging or menopause? Fertil Steril 2001;76:456-60

  6. Avis NE, Brockwell S, Randolph JF, et al. Longitudinal changes in sexual functioning as women transition through menopause: results from the Study of Womens Health Across the Nation. Menopause 2009;16:44252

  7. Nappi RE, Domoney C. Pharmacogenomics and sexuality: a vision. Climacteric 2013;16(Suppl 1):25-30

  8. Wierman ME, Nappi RE, Avis N, et al. Endocrine aspects of womens sexual function. J Sex Med 2010;7:561-85

  9. Wierman ME, Auchus RJ, Haisenleder DJ, et al. Editorial: The new instructions to authors for the reporting of steroid hormone measurements. J Clin Endocrinol Metab 2014;99:4375

  10. Randolph JF Jr, Zheng H, Avis NE, Greendale GA, Harlow SD. Masturbation frequency and sexual function domains are associated with serum reproductive hormone levels across the menopausal transition. J Clin Endocrinol Metab 2015;100:258-66

El siguiente comentario es una traducción de una contribución original en Inglés enviada a los miembros el Agosto 26, 2013. La traducción ha sido gentilmente efectuada por el

Dr Peter Chedraui

Cambios en la resorción ósea durante la transición menopáusica

Sowers y colegas han investigado las posibles asociaciones entre los cambios en la resorción ósea durante la transición de la menopausia y las hormonas reproductivas, índice de masa corporal (IMC) y la etnia [1]. Se midieron en 918 mujeres afroamericanas, chinas, japonesas o caucásicas el Telopéptido-N del colágeno óseo Tipo I urinario (NTX), estradiol y la hormona folículo estimulante (FSH) anualmente por 8 años, periodo que abarcaría la transición de la menopausia. El NTX urinario comenzó a aumentar agudamente alrededor de 2 años antes de la menstruación final (MF), alcanzando su nivel máximo alrededor de 1 a 1.5 años después de la MF. Los niveles de NTX declinaron modestamente 2–6 años después de la MF, pero se mantuvieron alrededor de 20% más alto que antes de la transición a la menopausia. El aumento agudo de la FSH se produjo en conjunto con una fuerte disminución de los niveles de estradiol y poco después de que los niveles de FSH comenzaran a aumentar rápidamente. El incremento promedio del NTX urinario a lo largo de la transición de la menopausia fue mayor en las mujeres con IMC < 25 kg/m2 y menor en aquellas con un IMC > 30 kg/m2. Los aumentos del NTX fueron mayores en las mujeres japonesas y menores en las afroamericanas. Estas diferencias se atenuaron, pero no eliminaron, cuando el análisis se ajustó para co-variables, particularmente el IMC. Durante la transición de la menopausia, una disminución de la función ovárica que comienza alrededor de 2 años antes de la MF es seguido por un aumento de la resorción ósea y, posteriormente, por pérdida de hueso. La magnitud del aumento de la resorción ósea está inversamente asociada con el IMC. Las diferencias étnicas en los cambios en la resorción ósea se atenúan, pero no eliminan, por el ajuste para el IMC. Las diferencias étnicas en el IMC, y las diferencias étnicas correspondientes en la resorción ósea, parecen explicar gran parte de la variación étnica de pérdida de hueso durante la perimenopausia.


Las hormonas son esenciales para el desarrollo del esqueleto y para "mantener la salud ósea”. Durante la transición de la menopausia, los niveles de estrógeno disminuyen a una décima parte o menos de lo que había estado anteriormente. Como resultado, el hipotálamo estimula la glándula pituitaria a secrete más FSH y así aumentar la actividad ovárica. Por lo tanto, las concentraciones de FSH y hormona luteinizante (LH) en suero se incrementan diez veces con respecto a los valores antes de la fase de transición de la menopausia [2]. El estrógeno juega un papel importante en antagonizar el efecto de la hormona paratiroidea y reducir al mínimo la pérdida de hueso. Durante la etapa de la perimenopausia, hay un aumento en la resorción ósea debido a la disminución de la función ovárica. Se han llevado a cabo estudios similares que evalúan los efectos de las hormonas reproductivas en la salud ósea. Un IMC incrementado se cree que confiere protección contra la osteoporosis. Hay suficientes datos epidemiológicos disponibles para demostrar que el IMC se correlaciona con densidad mineral ósea elevada y que el IMC bajo provoca pérdida de hueso [3]. Durante la transición de la menopausia, la composición de la médula ósea gira a células adiposas y la actividad de los osteoclastos incrementa, resultando en resorción de hueso [4]. Los adipocitos y osteoblastos se originan a partir de un progenitor común, las células estromales mesenquimales pluripotenciales, y su diferenciación se regula a través de la vía del receptor activado del peroxisoma-proliferador (PPAR)-γ [5]. La activación del PPAR-γ conduce a la diferenciación de las células mesenquimales del estroma hacia adipocitos por sobre los osteoblastos [6]. Los adipocitos son fuentes importantes de producción de estrógeno en las mujeres postmenopáusicas, y se sabe que el estrógeno inhibe la resorción ósea por parte de los osteoclastos. Se ha propuesto que el aumento del tejido adiposo con aumento del IMC en mujeres postmenopáusicas da como resultado un aumento en la producción de estrógenos, supresión de los osteoclastos, y un aumento de la masa ósea [7]. El presente estudio muestra que la FSH y LH urinaria están incrementadas en mujeres con un IMC bajo y viceversa. El IMC no es el único factor que afecta la resorción ósea en la fase de transición a la menopausia; otros factores como la nutrición, el tabaquismo, la medicación, las enfermedades asociadas, la deficiencia de vitamina D, etc, también deberían tenerse en cuenta. La deficiencia de la vitamina D juega un papel importante en la absorción de calcio y la estimulación de la actividad osteoblástica [8]. Puede que no haya una correlación entre el aumento del IMC y la resorción ósea, ya que es el exceso de masa grasa más que el peso total del cuerpo lo que define la obesidad. Se necesitan más estudios para evaluar la correlación entre el IMC y la densidad de masa ósea. Las resultantes de estos estudios deben ser la reducción del riesgo de fractura y no solo la densidad de la masa ósea en la postmenopausia ya que son las fracturas que más nos preocupan, para dar a las mujeres postmenopáusicas una buena calidad de vida y no sólo años de vida.

Alka Kumar

Gynaecologist and Wellness Consultant, Secretary Indian Menopause Society, Nagpur Chapter India, Director of Shalaka Hospital and Menopause Clinic, Nagpur, India


  1. Sowers MR, Zheng H, Greendale GA, et al. Changes in bone resorption across the menopause transition: effects of reproductive hormones, body size, and ethnicity. J Clin Endocrinol Metab 2013;98:2854-63.

  2. Sowers MF, Zheng H, McConnell D, et al. Follicle stimulating hormone and its rate of change in defining menopause transition stages. J Clin Endocrinol Metab 2008;93:3958-64

  3. Paula FJ, Rosen CJ. Obesity, diabetes mellitus and last but not least, osteoporosis. Arq Bras Endocrinol Metabol 2010;54:150-7.

  4. Zhao LJ, Liu YJ, Liu PY, Hamilton J, Recker RR, Deng HW. Relationship of obesity with osteoporosis. J Clin Endocrinol Metab 2007;92:1640-6.

  5. Akune T, Ohba S, Kamekura S, et al. PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest 2004;113:84655.

  6. Pei L, Tontonoz P. Fats loss is bones gain. J Clin Invest 2004;113:8056.

  7. Kameda T, Mano H, Yuasa T, et al. Estrogen inhibits bone resorption by directly  +6inducing apoptosis of the bone-resorbing osteoclasts. J Exp Med 1997;186:48995.

  8. Zargar AH, Ahmad S, Masoodi SR, et al. Vitamin D status in apparently healthy adults in Kashmir Valley of Indian Subcontinent. Postgrad Med J 2007;83:713-16.

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