The hormonal profile and clinical manifestations of androgen deficiency in menopausal women and the current aspects associated with using hormone therapy

1. Labrie F., Martel C., Belanger A., Pelletier G. Androgens in women are essen-tially made from DHEA in each peripheral tissue according to intracrinology. J. Steroid Biochem. Mol. Biol. 2017; 168: 9-18. https://dx.doi.org/10.1016/j.jsbmb.2016.12.007.
2. Schifer L., Kempegowda P., Arlt W., O’Reilly M.W. Mechanisms in endocrinol-ogy: the sexually dimorphic role of androgens in human metabolic disease. Eur. J. Endocrinol. 2o17; 177(3): R125-43. https://dx.doi.org/10.1530/eje-17-0124.
3. Soman M., Huang L.C., Cai W.H., Xu J.B., Chen J.Y., He R.K. et al. Serum androgen profles in women with premature ovarian insufciency: a systematic re-view and meta-analysis. Menopause. 2019; 26(1): 78-93. https://dx.doi. org/10.1097/gme.0000000000001161.
4. Miller K.K., Biller B.M.K., Beauregard C., Lipman J.G., Jones J., Schoenfeld D. et al. Effects of testosterone replacement in androgen-deficient women with hy-popituitarism: a randomized, double-blind, placebo-controlled study. J. Clin. Endocrinol. Metab. 2006; 91(5): 1683-90.
5. Hovi L., Saarinen-Pihkala U.M., Taskinen M., Wilkstrőm A.M., Dunkel L. Sub-normal androgen levels in young female bone marrow transplant with ovarian disfunction, chronic GVHD and receiving glucocorticoid therapy. Bone Marrow Transplant. 2004; 33(5): 503-8.
6. Pluchino N., Carmignani A., Cubeddu A., Santoro A., Cela V., Errasti T. An-drogen therapy in women: for whom and when. Arch. Gynecol. Obstet. 2013; 288(4): 731-7. https://dx.doi.org/10.1007/s0040 4-013-2969-7.
7. Traish A.M., Vignozzi L., Simon J.A., Goldstein I., Kim N.N. Role of androgens in female genitourinary tissue structure and function: implications in the genitou-rinary syndrome of menopause. Sex. Med. Rev. 2018; 6(4): 558-71. https://doi.org/10.1016/j. sxmr.2018.03.005.
8. Wierman M.E., Basson R., Davis S.R., Khosla S., Miller K.K., Rosner W., Santoro N. Androgen therapy in women: an Endocrine Society Clinical Practice guideline. J Clin Endocrinol Metab. 2006 Oct; 91(10):3697-710. https://doi.org/10.1210/jc.2006-1121.
9. Pancer C., Guay A. Testosterone replacement therapy in naturally and surgi-cally menopausal women. J. Sex. Med. 2009; 6: 8-18.
10. Davis S.R., Davison S.L., Donath S., Bell R.J. Circulating androgen levels and self-reported sexual function in women. JAMA. 2005; 294(1): 91-6.
11. Randolph J.F. Jr., Zheng H., Avis N.E., Greendale G.A., Harlow S.D. Mas-turbation frequency and sexual function domains are associated with serum re-productive hormone levels across the menopausal transition. J. Clin. Endocrinol. Metab. 2015; 100(1): 258-66. https://dx.doi.org/10.1210/jc.2014-1725.
12. Rosen R., Brown C., Heiman J., Leiblum S., Meston C., Shabsigh R. et al. The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000; 26(2): 191-208. https://dx.doi.org/10.1080/009262300278597.
13. Wåhlin-Jacobsen S., Pedersen A.T., Kristensen E., Laessøe N.C., Lundqvist M., Cohen A.S. et al. Is there a correlation between androgens and sexual desire in women? J. Sex. Med. 2015; 12(2): 358-73. https://dx.doi.org/10.1111/jsm.12774.
14. Wierman M.E., Arlt W., Basson R., Davis S.R., Miller K.K., Murad M.H. et al. Androgen therapy in women: a reappraisal: an Endocrine Society clinical prac-tice guideline. J. Clin. Endocrinol. Metab. 2014; 99(10): 3489-510. https://dx.doi.org/10.1210/jc.2014-2260.
15. American Psychiatric Association. Diagnostic and statistical manual of men-tal disorders. Washington, DC: American Psychiatric Press; 1994.
16. Elraiyah T., Sonbol M.B., Wang Z., Khairalseed T., Asi N., Undavalli C. et al. Clinical review: The benefits and harms of systemic testosterone therapy in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 2014; 99(10): 3543-50. https://dx.doi.org/10.1210/jc.2014-2262.
17. Somboonporn W., Davis S., Seif M.W., Bell R. Testosterone for peri- and postmenopausal women. Cochrane Database Syst. Rev. 2005; (4): CD004509.
18. Islam R.M., Bell R.J., Green S., Page M.J., Davis S.R. Safety and efcacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data. Lancet Diabetes Endocrinol. 2019; 7(10): 754-66. https://dx.doi.org/10.1016/s2213 -8587(19)30189-5.
19. Davis S.R., Baber R., Panay N., Bitzer J., Perez S.C., Islam R.M. et al. Global consensus position statement on the use of testosterone therapy for women. J. Clin. Endocrinol. Metab. 2019; 104(10): 4660-6. https://dx.doi.org/10.1210/jc.2019-01603.
20. Prough R.A., Clark B.J., Klinge C.M. Novel mechanisms for DHEA action. J. Mol. Endocrinol. 2016; 56(3): R139-55. https://dx.doi. org/10.1530/jme-16-0013.
21. Li H., Sun J., Xu Z. Biotransformation of DHEA into 7alpha,15alpha-diOH-DHEA. Methods Mol. Biol. (Clifton, NJ) 2017; 1645: 289-95. https://dx.doi.org/10.1007/978-1-4939-7183-1_20.
22. Marsden J. British Menopause Society consensus statement: the risks and benefits of HRT before and after a breast cancer diagnosis. Post Reprod. Health. 2019; 25(1): 33-7. https://dx.doi. org/10.1177/2053369119825716.
23. Davis S.R. Cardiovascular and cancer safety of testosterone in women. Curr. Opin. Endocrinol. Diabetes Obes. 2011; 18(3): 198-203. https://dx.doi.org/10.1097/MED.0b013e328344f449.
24. Somboonporn W., Davis S.R. Testosterone efects on the breast: implications for testosterone therapy for women. Endocr. Rev. 2004; 25(3): 374-88. https://dx.doi.org/10.1210/er.2003-0016.
25. Misso M.L., Jang C., Adams J., Tran J., Murata Y., Bell R. et al. Adipose aromatase gene expression is greater in older women and is unafected by post-menopausal estrogen therapy. Menopause. 2005; 12(2): 210-5
26. Labrie F., Luu-The V., Labrie C., Belanger A., Simard J., Lin S.X., Pelletier G. Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr. Rev. 2003; 24(2): 152-82. https://dx.doi.org/10.1210/er.2001-0031.
27. Gera R., Tayeh S., Chehade H.E., Mokbel K. Does transdermal testosterone increase the risk of developing breast cancer? A systematic review. Anticancer Res. 2018; 38(12): 6615-20. https://dx.doi. org/10.21873/anticanres.13028.
28. Braunstein G.D., Sundwall D.A., Katz M., Shifren J.L., Buster J.E., Simon J.A. et al. Safety and efcacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Arch. Intern. Med. 2005; 165(14): 1582-9. https://dx.doi. org/10.1001/archinte.165.14.1582.
29. Buster J.E., Kingsberg S.A., Aguirre O., Brown C., Breaux J.G., Buch A. et al. Testosterone patch for low sexual desire in surgically menopausal women: a ran-domized trial. Obstet. Gynecol. 2005; 105(5, Pt 1): 944-52. https:// dx.doi.org/10.1097/01.AOG.0000158103.27672.0d.
30. Wallace I.R., McKinley M.C., Bell P.M., Hunter S.J. Sex hormone binding globulin and insulin resistance. Clin. Endocrinol. 2013; 78(3): 321-9. https://dx.doi.org/10.1111/cen.12086.
31. Ding E.L., Song Y., Manson J.E., Hunter D.J., Lee C.C., Rifai N. et al. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N. Engl. J. Med. 2009; 361(12): 1152-63. https://dx.doi.org/10.1056/NEJMoa0804381.
32. Worsley R., Robinson P.J., Bell R.J., Moufarege A., Davis S.R. Endogenous estrogen and androgen levels are not independent predictors of lipid levels in postmenopausal women. Menopause. 2013; 20(6): 640-5. https://dx.doi.org/10.1097/GME.0b013e318279bd4a.
33. Labrie F., Derogatis L., Archer D.F., Koltun W., Vachon A., Young D. et al. Efect of intravaginal prasterone on sexual dysfunction in postmenopausal women with vulvovaginal atrophy. J. Sex. Med. 2015; 12(12): 2401-12. https://dx.doi.org/10.1111/jsm.13045.
34. Davis S.R., Worsley R., Miller K.K., Parish S.J., Santoro N. Androgens and female sexual function and dysfunction-fndings from the fourth international consultation of sexual medicine. J. Sex. Med. 2016; 13(2): 168-78. https://dx.doi.org/10.1016/j. jsxm.2015.12.033.
35. Arlt W., Callies F., Koehler I., van Vlijmen J.C., Fassnacht M., Strasburger C.J. et al. Dehydroepiandrosterone supplementation in healthy men with an age-related decline of dehydroepiandrosterone secretion. J. Clin. Endocrinol. Metab. 2001; 86(10): 4686-92. https://doi.org/10.1210/jcem.86.10.7974.
36. Davis S.R., Shah S.M., McKenzie D.P., Kulkarni J., Davison S.L., Bell R.J. Dehydroepiandrosterone sulfate levels are associated with more favorable cogni-tive function in women. J. Clin. Endocrinol. Metab. 2008; 93(3): 801-8. https://dx.doi.org/10.1210/ jc.2007-2128.
37. Rosario E.R., Chang L., Head E.H., Stanczyk F.Z., Pike C.J. Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer’s disease. Neurobiol. Agin.g 2011; 32(4): 604-13. https://dx.doi.org/10.1016/j.neurobiolaging.2009.04.008.
38. Brown C.M., Mulcahey T.A., Filipek N.C., Wise P.M. Production of proin-flammatory cytokines and chemokines during neuroinflammation: novel roles for estrogen receptors alpha and beta. Endocrinology. 2010; 151(10): 4916–25. https://dx.doi.org/10.1210/en.2010-0371.
39. Drake E.B., Henderson V.W., Stanczyk F.Z., McCleary C.A., Brown W.S., Smith C.A. et al. Associations between circulating sex steroid hormones and cognition in normal elderly women. Neurology. 2000; 543: 599-603. https://dx.doi.org/10.1212/wnl.54.3.599.
40. Aleman A., Bronk E., Kessels R.P., Koppeschaar H.P., van Honk J. A single administration of testosterone improves visuospatial ability in young women. Psychoneuroendocrinology 2004; 29(5): 612-7. 1 https://dx.doi.org/10.1016/S0306-4530(03)00089-1.
41. Davis S.R., Jane F., Robinson P.J., Davison S.L., Worsley R., Maruff P., Bell R.J. Transdermal testosterone improves verbal learning and memory in post-menopausal women not on oestrogen therapy. Clin. Endocrinol. (Oxf). 2014; 81(4): 621-8. https://dx.doi.org/10.1111/cen.12459.
42. Clarke B.L., Khosla S. Androgens and bone. Steroids. 2009; 74(3): 296-305. 10.1016/j.steroids.2008.10.003.
43. Almeida M., Laurent M.R., Dubois V., Claessens F., O'Brien C.A., Bouillon R., Vanderschueren D., Manolagas S.C. Estrogens and Androgens in Skeletal Physiology and Pathophysiology. Physiol Rev. 2017 Jan; 97(1):135-87. https://dx.doi.org/10.1152/physrev.00033.2015.PMID: 27807202.
44. Barrett-Connor E., Young R., Notelovitz M., Sullivan J., Wiita B., Yang H.M. Nolan J. A two-year, double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. Effects on bone mineral density, symptoms and lipid profiles. J. Reprod. Med. 1999; 44(12): 1012-20.
45. Popat V.B., Calis K.A., Kalantaridou S.N., Vanderhoof V.H., Koziol D., Troendle J.F. et al. Bone mineral density in young women with primary ovarian in-sufficiency: results of a three-year randomized controlled trial of physiological transdermal estradiol and testosterone replacement. J. Clin. Endocrinol. Metab. 2014; 99(9): 3418-26. https://dx.doi.org/10.1210/jc.2013-4145.
46. Rariy C.M., Ratcliffe S.J., Weinstein R. et al. Higher serum free testosterone concentration in older women is associated with greater bone mineral density, lean body mass, and total fat mass: the cardiovascular health study. J. Clin. En-docrinol. Metab. 2011; 96: 989–96.
47. Dobs A.S., Nguyen T., Pace C., Roberts C.P. Differential effects of oral estro-gen versus oral estrogen-androgen replacement therapy on body composition in postmenopausal women. J. Clin. Endocrinol. Metab. 2002; 87(4): 1509-16. https://dx.doi.org/10.1210/jcem.87.4.8362.

Received 19.05.2020

Accepted 22.05.2020