The following is a collection of medical article abstracts, i.e. summaries, that are related to the subject of androgens and female sexuality. This information is not directed at the casual reader but rather women seeking to better understand their own sexual dissatisfaction when their doctors are unable to help them. It may help women get the necessary medical treatment for conditions related to androgen deficiency and female sexuality. Towards the bottom I have included abstracts that address the possible risks associated with hormone replacement therapies and cancer.
New information is being published almost daily on this subject so you may want to search for the latest medical information pertaining to women and androgens at PubMed. Simply enter "women androgens" into the search box that appears at the top of your screen after you click the link.
The following online medical dictionaries may be of help when reading this medical information:
http://www.nlm.nih.gov/medlineplus/mplusdictionary.html
http://www.medterms.com/script/main/hp.asp
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Source: Sex Health. 2006 May;3(2):73-8.
Title: A clinical update on female androgen insufficiency--testosterone testing and treatment in women presenting with low sexual desire.
Authors: Burger HG, Papalia MA.
The diagnosis of female androgen deficiency syndrome is suggested by complaints of a diminished sense of well being, persistent unexplained fatigue and decreased sexual desire, sexual receptivity and pleasure in a woman who is oestrogen (estrogen) replete [replete = abundantly supplied] and in whom no other significant contributing factors can be identified. The diagnosis is supported by the finding of low circulating concentrations of free testosterone. Barriers to its recognition include the non-specificity of the symptoms and methodological problems due to insensitive testosterone assays [test methods]. Barriers to its treatment include the unavailability of satisfactory forms of testosterone for administration to women and lack of data regarding long-term safety. Although several conditions lead to clear-cut androgen deficiency, such as hypopituitarism, adrenal and ovarian insufficiency, glucocorticoid therapy and use of oral contraceptives and oral oestrogens, it is important for clinicians to recognize that in normal women, androgen levels decline by 50% from the early 20s to the mid 40s, and hence age-related androgen insufficiency may occur in women in their late 30s and 40s, as well as postmenopausally. Satisfactory measurements of free testosterone requires a sensitive and reliable assay for total testosterone, and quantitation of sex hormone binding globulin, from which free testosterone is readily calculated. Adverse effects of testosterone treatment are few if replacement is monitored to achieve physiological [normal or average] circulating testosterone concentrations. Currently, available methods include testosterone implants and testosterone creams, and transdermal patches and sprays are in development.
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Source: Maturitas. 2006 Jul 3; [Epub ahead of print]
Title: The benefits of androgens combined with hormone replacement therapy regarding to patients with postmenopausal sexual symptoms.
Authors: de Paula FJ, Soares JM Jr, Haidar MA, Lima GR, Baracat EC.
Objective: To evaluate the benefits and risks of hormone replacement therapy (HRT) combined with methyltestosterone (MT) in postmenopausal women with sexual dysfunction.
Design: This study was a randomized, double-blind, placebo-controlled and crossover trial. Eighty-five women using HRT were divided into four treatment groups: GI-HRT plus placebo for 4 months; GII-HRT plus MT 2.5 mg/day for 4 months; GIII-HRT plus placebo for 2 months and then replaced with HRT plus MT 2.5 mg/day for 2 months; GIV-HRT plus MT 2.5 mg/day and then replaced with HRT plus placebo for 2 months. Blood was collected at baseline, after 2 months (T1) and 4 months (T2) of treatment for hormone determinations of estradiol, FSH, total and free testosterone, GOT, GPT, glucose, total and fractions of cholesterol and triglycerides. All participants answered clinical questions and a validated questionnaire of modified McCoy's sex scale.
Results: The association of HRT with MT 2.5 mg/day did not significantly change liver enzymes or increase cardiovascular risk factors. The patients of GII, GIIII and GIV when using MT presented amelioration of sex symptoms, mainly satisfaction and desire (p < 0.01); however, GIII at T1 (1.3 ± 0.3) presented similar problem score results as compared to GIII at T2 (1.5 ± 0.6).
Conclusion: All data suggest that combined HRT-androgen therapy may be beneficial for postmenopausal women receiving HRT who continue to complain of sexual difficulties or for postmenopausal women with sexual complaints who are not undergoing estrogen therapy.
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Source: Curr Opin Obstet Gynecol. 2006 Aug;18(4):427-32.
Title: Androgen and menopause.
Authors: Somboonporn W.
PURPOSE OF REVIEW: Androgen therapy is being increasingly used in the management of postmenopausal women. The most common indication is to improve sexual function. The aim of this review is to evaluate current knowledge pertaining to testosterone and sexual function in postmenopausal women.
RECENT FINDINGS: The change of testosterone levels during the menopause transition remains controversial. A correlation of endogenous testosterone levels and sexual function is still inconclusive. A Cochrane Review and recent randomized control trials have, however, consistently demonstrated that short-term testosterone therapy in combination with traditional hormone therapy regimens improves sexual function in postmenopausal women, particularly surgically menopausal women with hypoactive [hypo = low or deficient] sexual desire disorder. An adverse effect on the lipid [ Lipid = fat relating to cardiovascular disease] profile has been identified which appears to be mostly associated with oral methyltestosterone. Data for other effects of testosterone and long-terms risks are lacking. Testosterone may act in a variety of ways in different tissues. This is, however, an area that requires further investigation.
SUMMARY: Testosterone therapy is a promising option for treating women with hypoactive sexual desire disorder after surgical menopause. Two remaining questions need to be answer: who is most likely to benefit from testosterone therapy and what are the long-term health risks?
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Source: Gynecol Endocrinol. 2006 Jun;22(6):318-23
Title: Hypoactive sexual desire disorder in postmenopausal women.
Authors: Nappi RE, Wawra K, Schmitt S.
Decreases in sex hormone levels with menopause may bring about a number of consequences in women's general health and sexual well-being, especially when levels decline suddenly and prematurely, as in surgical menopause. In addition to the well-established role of estrogens in preserving the biological basis of sexual response, there is emerging evidence that androgens are significant independent determinants affecting sexual desire, activity and satisfaction, as well as mood, energy and other components of women's health. Hypoactive sexual desire disorder (HSDD), a persistent absence of sexual fantasies or thoughts and/or desire for and receptivity to sexual activity that causes personal distress, is experienced by some postmenopausal women. Even though conventional hormone therapy with estrogens or estrogens and progestogens may be effective for vaginal atrophy, increasing vaginal lubrication and reducing dyspareunia, it has not been shown to consistently increase sexual desire or activity and many women with sexual dysfunction remain unresponsive. Several recent, large, phase III studies have shown that the addition of transdermal testosterone to conventional hormone therapy can be helpful in surgically menopausal women presenting with HSDD. After 24 weeks of treatment in these studies, testosterone-treated women experienced significantly greater increases in satisfying sexual activity and sexual desire, and greater decreases in distress, than placebo-treated women. Accurate clinical assessment and individualized management of sexual symptoms are fundamentally important for all menopausal women with HSDD or other sexual problems.
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Source: Growth Horm IGF Res. 2006 Jul;16 Suppl A:S109-17. Epub 2006 Apr 24
Title: Androgen insufficiency in women.
Authors: Braunstein GD.
Androgens are directly secreted by the ovaries and adrenals in women, and androgen precursors from these glands are converted in a variety of peripheral tissues into androgens. The major androgen in women is testosterone, and its action in target tissues can be mediated through the androgen receptor or through the estrogen receptor after aromatization to estradiol. Low sexual desire that causes personal distress (or hypoactive sexual desire disorder [HSDD]) is the most common form of female sexual dysfunction, and androgen insufficiency is one cause of this problem. In addition to a low libido, the clinical construct of the female androgen insufficiency syndrome includes the presence of persistent, unexplained fatigue and a decreased sense of well-being. Although there is conflicting information about the relationship between serum testosterone concentrations and sexual desire, multiple randomized, double-blind, placebo-controlled treatment trials have demonstrated that testosterone improves libido significantly more than placebo. Doses that provide physiologic to slightly supraphysiologic serum free or bioavailable testosterone concentrations are safe and associated with only mild androgenic side effects of acne and hirsutism. Oral, but not parenteral or transdermal, testosterone may decrease high-density lipoprotein cholesterol. At present, no testosterone preparation has been approved by the FDA for the treatment of low sexual desire (HSDD), so all such therapy is considered to be off-label use at this time.
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Source: J Steroid Biochem Mol Biol. 2006 Jun;99(4-5):182-8. Epub 2006 Apr 18.
Title: Androgen glucuronides, instead of testosterone, as the new markers of androgenic activity in women.
Authors: Labrie F, Belanger A, Belanger P, Berube R, Martel C, Cusan L, Gomez J, Candas B, Castiel I, Chaussade V, Deloche C, Leclaire J.
Despite the long series of cohort studies performed during the last 20 years, the correlation between serum testosterone and any clinical situation believed to be under androgen control in women has remained elusive. This is likely related to the recent finding that the androgens made locally in large amounts in peripheral tissues from the precursor dehydroepiandrosterone (DHEA) act in the same cells where synthesis takes place and are not released in significant amounts in the circulation, thus making unreliable the measurement of serum testosterone as marker of total androgenic activity. The objective is to determine if serum androgen glucuronides can be replaced by testosterone or another steroid as measure of androgenic activity. Since the glucuronide derivatives of androgens are the obligatory route of elimination of all androgens, these metabolites were measured by liquid chromatography tandem mass spectrometry under basal conditions in 377 healthy postmenopausal women aged 55-65 years as well as in 47 premenopausal women aged 30-35 years while testosterone was assayed by gas chromatography mass spectrometry. No correlation was found between the serum concentration of testosterone and that of androsterone glucuronide (ADT-G) or androstenediol glucuronide (3alpha-diol-G), the androgen metabolites which account for the total pool of androgens. The present data show that measurement of the total pool of androgens reflected by the serum levels of ADT-G and 3alpha-diol-G cannot be replaced by serum testosterone or any other steroid, including DHEA or DHEA sulphate. These findings may have implications for women with androgen deficiency involving osteoporosis, obesity, type 2 diabetes, sexual dysfunction, loss of muscular strength and a series of other clinical situations affecting women's health. Measuring ADT-G and 3alpha-diol-G might identify cases of true androgen deficiency and provide an opportunity to offer appropriate androgen therapy.
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Source: J Clin Endocrinol Metab. 2006 May;91(5):1683-90. Epub 2006 Feb 14
Title: Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study.
Authors: Miller KK, Biller BM, Beauregard C, Lipman JG, Jones J, Schoenfeld D, Sherman JC, Swearingen B, Loeffler J, Klibanski A.
CONTEXT: Hypopituitarism in women is characterized by profound androgen deficiency due to a loss of adrenal and/or ovarian function. The effects of testosterone replacement in this population have not been reported.
OBJECTIVE: The objective of the study was to determine whether physiologic testosterone replacement improves bone density, body composition, and/or neurobehavioral function in women with severe androgen deficiency secondary to hypopituitarism.
DESIGN: This was a 12-month randomized, placebo-controlled study. SETTING: The study was conducted at a general clinical research center.
STUDY PARTICIPANTS: Fifty-one women of reproductive age with androgen deficiency due to hypopituitarism participated.
INTERVENTION: Physiologic testosterone administration using a patch that delivers 300 microg daily or placebo was administered.
MAIN OUTCOME MEASURES: Bone density, fat-free mass, and fat mass were measured by dual x-ray absorptiometry. Thigh muscle and abdominal cross-sectional area were measured by computed tomography scan. Mood, sexual function, quality of life, and cognitive function were assessed using self-administered questionnaires.
RESULTS: Mean free testosterone increased into the normal range during testosterone administration. Mean hip (P = 0.023) and radius (P = 0.007), but not posteroanterior spine, bone mineral density increased in the group receiving testosterone, compared with placebo, as did mean fat-free mass (P = 0.040) and thigh muscle area (P = 0.038), but there was no change in fat mass. Mood (P = 0.029) and sexual function (P = 0.044) improved, as did some aspects of quality of life, but not cognitive function. Testosterone at physiologic replacement levels was well tolerated, with few side effects.
CONCLUSIONS: This is the first randomized, double-blind, placebo-controlled study to show a positive effect of testosterone on bone density, body composition, and neurobehavioral function in women with severe androgen deficiency due to hypopituitarism.
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Source: Exp Clin Endocrinol Diabetes. 2006 Apr;114(4):182-7
Title: Is it necessary to measure free testosterone to assess hyperandrogenemia in women? The role of calculated free and bioavailable testosterone.
Authors: Mueller A, Dittrich R, Cupisti S, Beckmann MW, Binder H.
Hirsutism in women is defined as excessive facial and/or body terminal hairs showing a masculine distribution; the condition affects approximately 7% of women of reproductive age, and chronic anovulation is a common problem for infertile couples, with a rate of 20-25%. There is a general consensus that these women should be evaluated endocrinologically, as many are found to have an androgen excess (AE) disorder. Free testosterone (FT) is the most prevalent marker in women with androgen excess, but the reference measurement procedures for FT are time-consuming and complex manual procedures that are not routinely practicable in large laboratories. Recently, models have been developed for calculating FT from total testosterone (TT), sex hormone binding globulin (SHBG), and albumin. These calculated values have been found to correlate closely with values estimated using the reference measurement procedures. This study compared measured endocrinological parameters--TT, free testosterone (aFT) by analogue ligand immunoassay method, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), (SHBG), And calculated parameters--calculated free testosterone (cFT), calculated bioavailable testosterone (cBT), and the free androgen index (FAI) in hirsute women and women with polycystic ovary syndrome (PCOS)--with the values in control individuals. A modified Ferriman-Gallwey score was use to describe the hirsutism pattern. No differences were observed when the measured hormone parameters were compared, while the calculated parameters were significantly increased in women in the hirsutism and PCOS groups in comparison with the values in the control group. Calculate parameters mat be more appropriate markers for assessing hyperandrogenemia in women in comparison with measured values of simple enzyme immuno-assays. These calculated values may be capable of replacing the values estimated using reference measurement procedures, so that time-consuming and complex manual procedures for measuring free testosterone with the reference methods may be dispensable in clinical practice.
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Source: Semin Reprod Med. 2006 Apr;24(2):115-24
Title: Testosterone therapy for postmenopausal women: efficacy and safety.
Authors: Somboonporn W.
The treatment of postmenopausal women with a variety of androgen formulations is increasing, despite the lack of clear guidelines regarding the diagnosis of androgen insufficiency. This review summarizes evidence on the efficacy and safety of adding testosterone to hormone therapy in postmenopausal women. Fair to good evidence exists that the use of testosterone in combination with hormone therapy has both benefits and risks. The benefits are an improvement in sexual function with various regimens of testosterone use (good evidence), an improved sense of well-being with transdermal testosterone (fair evidence), and a reduction in triglyceride levels with methyl testosterone (fair evidence). The most consistent risk is a reduction in high-density lipoprotein (HDL) cholesterol, particularly with methyl testosterone (good evidence). There has been insufficient reporting of other side effects; hence, testosterone therapy should be used with caution. The use of testosterone may be justified in specific clinical circumstances and should be limited to short-term use; long-term studies are not available. Close surveillance for HDL cholesterol and other side effects is necessary.
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Source: Semin Reprod Med. 2006 Apr;24(2):78-85
Title: Measurement of androgens in women.
Authors: Stanczyk FZ.
Much of our knowledge about the physiologic role of androgens in women is based on measurements, primarily in serum, using radioimmunoassay (RIA) methodology that involves purification of the analyte by organic solvent extraction and column chromatography. Although the extraction/chromatographic RIA is highly reliable when properly validated, it is time consuming and costly. For this reason, direct RIA methods were developed. Subsequently, the radioactive marker was replaced by other labels that have been used in direct chemiluminescent, fluorescent, and enzyme immunoassays on autoanalyzers. Although direct immunoassays are simple and rapid, they are seldom thoroughly validated, and generally lack the sensitivity and specificity for reliable measurements of testosterone levels found in postmenopausal serum. In recent years there has been increased use of mass spectrometry assay methods to quantify steroid hormones. These methods are touted to become the gold standard for all steroid hormone measurements. Because urine contains predominantly glucuronidated androgens, multistep procedures are required for the measurement, which is not practical for diagnostic testing. Androgens also can be measured in saliva, but major methodologic problems are associated with the measurements. In addition, there is a misconception that salivary testosterone levels reflect free testosterone levels in serum.
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Source: Semin Reprod Med. 2006 Apr;24(2):71-7
Title: Androgen physiology.
Authors: Davison SL, Bell R.
Androgen receptors are present in numerous tissues throughout the female body, and knowledge of the specific actions of androgens at different sites is increasing, along with the understanding of their contribution to various pathophysiological states. This article reviews the physiology of androgens (testosterone and dihydrotestosterone) and immediate androgen precursors (dehydroepiandrosterone [DHEA], dehydroepiandrosterone sulfate [DHEAS], and androstenedione), with specific reference to the androgen receptor, production and metabolism of C- (19) steroids, circulating androgen concentrations, and androgen actions. In addition, the evidence for physiological modulation of androgens including circadian variation, cyclical variation, age, and natural menopause is reviewed.
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Source: Fertil Steril. 2002 Apr;77 Suppl 4:S3-5.
Title: Androgen production in women.
Authors: Burger HG.
OBJECTIVE: To describe the sources, production rates, circulating concentrations, and regulatory mechanisms of the major androgen precursors and androgens in women.
DESIGN: Review of the major published literature.
RESULT(S): Quantitatively, women secrete greater amounts of androgen than of estrogen. The major circulating steroids generally classified as androgens include dehydroepiandrosterone sulphate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T), and dihydrotestosterone in descending order of serum concentration, though only the latter two bind the androgen receptor. The other three steroids are better considered as pro-androgens. Dehydroepiandrosterone is primarily an adrenal product, regulated by adrenocorticotropic hormone (ACTH) and acting as a precursor for the peripheral synthesis of more potent androgens. Dehydroepiandrosterone is produced by both the ovary and adrenal, as well as being derived from circulating DHEAS. Androstenedione and testosterone are products of the ovary and the adrenal. Testosterone circulates both in its free form, and bound to protein including albumin and sex steroid hormone-binding globulin (SHBG), the levels of which are an important determinant of free testosterone concentration.
CONCLUSION(S): The postmenopausal ovary is an androgen-secreting organ and the levels of testosterone are not directly influenced by the menopausal transition or the occurrence of menopause. Dihydrotestosterone (DHT) is primarily a peripheral product of testosterone metabolism. Severe androgen deficiency occurs in hypopituitarism, but other causes may lead to androgen deficiency, including Addison's disease, corticosteroid therapy, chronic illness, estrogen replacement (leads to elevated SHBG and, therefore, low free testosterone), premenopausal ovarian failure, or oophorectomy.
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Source: Semin Reprod Med. 2006 Apr;24(2):71-7
Title: Androgen Physiology
Authors: Davison SL, Bell R.
Androgen receptors are present in numerous tissues throughout the female body, and knowledge of the specific actions of androgens at different sites is increasing, along with the understanding of their contribution to various pathophysiological states. This article reviews the physiology of androgens (testosterone and dihydrotestosterone) and immediate androgen precursors (dehydroepiandrosterone [DHEA], dehydroepiandrosterone sulfate [DHEAS], and androstenedione), with specific reference to the androgen receptor, production and metabolism of C-19 steroids, circulating androgen concentrations, and androgen actions. In addition, the evidence for physiological modulation of androgens including circadian variation, cyclical variation, age, and natural menopause is reviewed.
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Source: Endokrynol Pol. 2005;56(6):1016-1020
Title: Androgen deficiency in women
Authors: Jakiel G, Baran A.
Androgens are defined as the steroids having a binding affinity of the androgen receptor. In the reproduction age a daily production of testosterone is equally divided between the ovaries and adrenal and local tissue conversion of androstenedione and DHEA. After menopause the 80% of testosterone is produced in ovaries, but majority of precursors for peripheral conversion is adrenal origin. Androgen receptors are present throughout in the body; over 200 cellular actions of androgens have been described. Androgenic action is determined by quantitative level of the androgen present in the circulation, its degree of binding to proteins, the degree of interconversion to other androgens and estrogens, and the biological potency and androgen receptor binding affinity of the androgen. The most common clinical symptoms of androgen deficiency are the reduction of sex motivation, sex fantasy, sex enjoyment, sex arousal, vaginal vasocongestion, but also reduction of pubic hair, bone mass, muscle mass, worsening of quality of life (mood, affect, energy), more frequent vasomotors symptoms, insomnia, depression, headache. All these signs and symptoms can be multifactorial. Most common conditions associated with hypoandrogenism in women are hypothalamic-pituitary abnormalities, lack or insufficiency of ovaries, adrenal insufficiency, glucocorticoid therapy, exogenous estrogen administration. Besides the clinical picture the free testosterone measuring is important for diagnosis. The method of choice of this measure is equilibrium dialysis assay. Despite of clinical importance of androgen insufficiency in women, none of methods of androgen substitution is approved by FDA.
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Source: Eur J Endocrinol. 2006 Jan;154(1):1-11.
Title: Androgen therapy in women.
Authors: Arlt W.
Androgens in women either derive from direct ovarian production or from peripheral conversion of the adrenal sex steroid precursor, dehydroepiandrosterone, towards active androgens. Therefore, loss of adrenal or ovarian function, caused by Addison's disease or consequent to bilateral oophorectomy, results in severe androgen deficiency, clinically often associated with a loss of libido and energy. Importantly, physiological [normal] menopause does not necessarily lead to androgen deficiency, as androgen synthesis in the ovaries may persist despite the decline in estrogen production. However, the definition of female androgen deficiency, as recently provided by the Princeton consensus statement, is not precise enough and may lead to over-diagnosis due to the high prevalence of its diagnostic criteria: androgen levels below or within the lower quartile of the normal range and concurrent sexual dysfunction. Importantly, physiological [normal] menopause is not necessarily associated with androgen deficiency and therefore does not routinely require androgen therapy. Current replacement options include transdermal testosterone administration or dehydroepiandrosterone treatment, both of which have been shown to result in significant improvements, in particular in libido and mood, while effects on body composition and muscular function are not well documented. It is important to keep in mind that the number of randomized controlled trials is still limited and that currently none of the available preparations is officially approved for use in women. Currently, androgen replacement should be reserved for women with severe androgen deficiency due to an established cause and matching clinical signs and symptoms.
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