The proposed key symptoms of the female androgen insufficiency syndrome (FAIS) include reduced libido, diminished well being and lowered mood. In the SWAN study, changes in hormone levels across the menopausal transition were reported in 3029 women aged between 42 and 54 years from five ethnic groups (Lasley et al., 2002). Androgens also play an important role in bone physiology. Some researchers argue that the condition causes symptoms such as tiredness and loss of sexual interest. Testosterone is a hormone known as an androgen. This formulation is specifically designed for men and the safety and efficacy in women are unknown. Testosterone levels also show diurnal variation with an early morning peak. If treatment with DHEA is considered, DHEAS should be below the normal female range. Clearly there is a need for a reliable, commercially available assay. Women who choose to have testosterone therapy need to consult a doctor who is knowledgeable in this area, can give accurate and up-to-date advice, and who can monitor their treatment properly. There is no established level of free testosterone below which a woman can be said to be deficient, nor any level to which a woman should be restored that determines that she is replete. Adrenal androgen secretion is stimulated by adrenocorticotropic hormone (ACTH) while ovarian androgen secretion is stimulated by LH. The State of Victoria and the Department of Health shall not bear any liability for reliance by any user on the materials contained on this website. It is essential that women be well-estrogenized prior to androgen replacement in order to avoid the unwanted side effects of unopposed androgens. However, in women suffering from dyspareunia secondary to atrophic vaginitis, the use of estrogen replacement may improve libido following the relief of vaginal symptoms (Studd et al., 1977a). (2002) found no difference in levels of total and free testosterone, DHEAS, DHT, androstenedione and SHBG in 309 surgically menopausal women with low libido on hormone therapy (HT) compared with naturally menopausal women with normal libido also on HT. Thus, tissue sensitivity to androgens will vary according to the amount and activity of these enzymes, which may vary considerably between individuals and does not correlate with serum T levels. It is important to consider this a working definition, on which to base future research. DHT is derived almost entirely from peripheral conversion of testosterone by the enzyme 5α-reductase. However, the measuring of testosterone levels is limited by the lack of routinely available sensitive assays for both total and free testosterone. Mouse studies suggest that aromatization of testosterone to estrogen within the brain is responsible for sexual activity in rodents (Ogawa et al., 2000; Simpson et al., 2000). Only 1–2% of total circulating testosterone is in the unbound form (free T). Many of these symptoms are non-specific and are common to other disorders such as depression, and are affected by multiple variables including socio-economic, environmental and life circumstances. Additional biochemical investigations such as liver function tests should be based on clinical judgement. Conversely, it has been suggested that parenteral T therapy may be associated with improved cardiovascular risk (Yue et al., 1995; Worboys et al., 2001). DHEA is produced by the adrenals (50%) and the ovaries (20%) from pregnenolone and from peripheral conversion of DHEAS (30%). (, Bachmann GA, Bancroft J, Braunstein G et al. Androstenedione and testosterone are products of the ovary and the adrenal. (1980) conducted a 10 week double blind study of 40 naturally menopausal women randomized to one of four treatment groups: conjugated equine estrogen (CEE) 0.625 mg, CEE 0.625 mg plus medroxyprogesterone acetate (MPA) 5 mg, CEE 0.625 mg plus methyltestosterone (MT) 5 mg or placebo. Elevations in estradiol (as occurs during pregnancy), hyperthyroidism and liver disease cause a marked increase in SHBG levels with a subsequent decrease in serum free T levels, whereas hypothyroidism, obesity, and hyper-insulinemia are associated with decreased SHBG levels. Despite the complexities involved with defining FAIS, the symptoms have been reported to respond well to testosterone replacement. Shifren et al. Patients with CAH due to steroid 21-hydroxylase gene (CYP21A2) mutations usually have very high levels of androstenedione, often 5- to 10-fold elevations. Premenopausal women — The major androgens in the serum of normal cycling women are dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione, testosterone, and dihydrotestosterone (DHT), in descending order of serum concentrations . So next time you’re reaching for that donut in the break room, try to remember that sugar is not a friend to any of your hormones. Oral androgen therapy has been associated with an adverse lipid profile, with a reduction in high density lipid (HDL) levels, and is not an ideal form of androgen replacement. There are currently no approved androgen therapies available for treatment of sexual dysfunction in women. The risk of side effects depends on many factors, such as the treatment method, the dosage and the length of the therapy. Causes of androgen deficiency in women. With the onset of adrenarche, androstenedione raises gradually, a process that accelerates with the onset of puberty, reaching adult levels around age 18. On the other hand, Myers et al. Women received either estradiol implants 50 mg alone or estradiol 50 mg with testosterone 50 mg. The proposed key symptoms of the female androgen insufficiency syndrome (FAIS) include reduced libido, diminished well being and lowered mood. These effects may be due to direct androgen actions or be due in part to estradiol biosynthesis from testosterone in the vascular bed (Harada et al., 1999). (2003) compared four different commercial direct testosterone immunoassays with extraction chromatography RIA and also concluded that commercial immunoassays are unreliable for measuring testosterone levels in female serum samples. In particular, genes coding for testosterone and DHT were located in the vicinity of different genomic regions depending on whether the person was of black or white origin. Androstenedione is produced in equal amounts by the adrenals and the ovaries from cholesterol via progesterone. Insulin Resistance. There is an ∼50% fall in both total and free testosterone between the ages of 20 and 40–45, with only a very slight fall in circulating concentrations thereafter. A recent consensus conference recommended that the female androgen insufficiency syndrome (FAIS) is defined by a pattern of clinical symptoms and signs in the presence of decreased bioavailable testosterone and normal estrogen status (Bachmann et al., 2002). Sherwin et al. The risks of testosterone therapy in those with a history of VTE are currently unclear and testosterone therapy is best avoided in this group of women. These characteristics are extremely unlikely to develop if dosage is monitored appropriately and if testosterone levels are maintained within the normal range for young adult women of reproductive age. The most significant biologically active androgen in males and females is testosterone. Androstenedione appears to be more likely to cause virilizing side effects than DHEA because supraphysiological testosterone levels are attained with the administration of androstenedione (Kicman et al., 2003). Oral androgen therapy is associated with suppressed HDL levels and is not ideal for long-term administration. There is no definitive answer on what constitutes normal T levels for women. This outcome may reflect inadequate treatment time, too small study numbers, inability of MT to be aromatized, the effects of CEE on raising SHBG levels with a subsequent decline in free T levels or no true difference of therapy. Clinical symptoms of the proposed deficiency state (see Table I) may include decreased libido, sexual receptivity and pleasure; a diminished sense of well being; dysphoric mood and/or blunted motivation; and persistent unexplained fatigue. No specific test for androgen deficiency exists. No clinical human studies to date have differentiated whether any of these effects are AR or ER mediated, or both. All treatment groups had an increase in BMD at the hip and spine, but with the higher dose combination of estrogen and testosterone having the greatest effect (Barrett-Connor et al., 1999). Results: 44 patients were studied (27 females); mean age was 35.5±13.2 years. Other researchers believe that there is not enough evidence to support the existence of the condition. The symptoms of androgen deficiency are similar to those of many other conditions, such as: Your doctor may need to assess you for these conditions. If you are a female with the levels of Androstenedione lower than the clinical range according to your age and phase, it can indicate the following conditions: – The incapability of the adrenal glands to work the way that it should. With increasing age there tends to be a reduction in libido, with a reported decline immediately following oophorectomy (Nathorst-Boos et al., 1992). If this patient had a blood sample taken to measure androstenedione level at 10:00, the result of 9.9 (nmol/l) would suggest that levels over the 24 hours would all be acceptable. Testosterone appears to be important for its vasomotor effects (Worboys et al., 2001), enhancing vaginal blood flow and lubrication (Leiblum et al., 1983; Tuiten et al., 2000). It is made in the adrenal glands and gonads (testes in males and ovaries in females). Foods high in fiber can … In addition, circulating SHBG levels fall across (Zumoff et al., 1995) the menopausal transition with a subsequent rise in free androgen levels (Burger et al., 2000). Alternatively, antidepressants may worsen sexual dysfunction as a side effect of treatment and a change of antidepressant therapy may be required to clarify the predominant factor. Information about a therapy, service, product or treatment does not in any way endorse or support such therapy, service, product or treatment and is not intended to replace advice from your doctor or other registered health professional. If low levels are found, a morning cortisol level should be checked to investigate for adrenal insufficiency. In another RPCT with a cross-over design of 45 premenopausal women presenting with low libido, treatment with transdermal testosterone significantly improved sexual motivation, fantasy, frequency of sexual activity, pleasure, orgasm and satisfaction (Goldstat et al., 2003). The low plasma oestrone levels do not appear to be due to impaired conversion of androstenedione to oestrone, but are probably the result of the low plasma androstenedione levels themselves. Hormones are chemical messengers that communicate with tissues in the body to bring about many different changes. Following administration, serum concentrations are very variable and short-lived, and its use is not recommended in women (Buckler et al., 1998). (2000) conducted a 12 week study in estrogen-replaced, surgically menopausal women with decreased libido that demonstrated significant improvements in sexual function with physiological testosterone therapy. The risk of breast cancer in premenopausal women in relation to endogenous free T levels and exposure to exogenous testosterone has not been assessed to date. It shows diurnal variation and a midcycle elevation in concentration, which parallels the midcycle peak of estradiol. Such absolute levels are not likely to be established because of the large inter-individual variability and the intracrinology of androgens in women. Many blood and salivary tests for testosterone levels lack accuracy when measuring the low levels present in women, though some sensitive testosterone tests are now available. Hepatic side effects of androgen therapy in women are predominantly associated with the use of oral methyltestosterone (MT) and other 17-alkylated derivatives in supraphysiological doses. Following treatment with combined subcutaneous implants with estradiol 40 mg and T 100 mg, no significant changes were seen in total serum cholesterol, triglyceride or cholesterol subfractions (Burger et al., 1984). In contrast, transdermal administration of testosterone at doses comparable to premenopausal hormone production has not been associated with virilization (Shifren et al., 2000; Goldstat et al., 2003). Androstenedione levels were slightly higher in testes (2.21 +/- 2 ng/g) than in ovaries (1.53 +/- 1.32 ng/g). Free/bioavailable T levels or total T with SHBG and calculated free T should be monitored regularly with the aim of maintaining these values at least within the normal range for premenopausal women, to reduce the likelihood of side effects. Testosterone is secreted by the adrenals (25%), the ovaries (25%) and by peripheral conversion of circulating androgens, predominantly androstenedione (50%). Diets low in sugar can help reduce androgen levels. There is evidence of a relationship between androgen deficiency and lowered mood and sense of well being which improves with testosterone therapy in pre- and postmenopausal women. There is little evidence that any of the added progestins improve or worsen sexual problems when given with estrogen (Walling et al., 1990; Shulman et al., 2002). On the other hand, Couzinet et al. In premenopausal women, adequate estrogenization is likely in the presence of regular cycles (periods every 21 to 35 days) and the absence of hot flushes or vaginal dryness. In addition, the risk of breast cancer is not increased in women with PCOS defined by a hyperandrogenic state. Contraindications to testosterone therapy include pregnancy and lactation, androgen-dependent neoplasia, severe acne and/or hirsutism, androgenic alopecia, a history of polycystic ovary syndrome and situations where increased libido is an undesirable consequence. The increased bone resorption can be corrected by oestrogen therapy and the malabsorption of calcium can be corrected with 1 α -OHD 3 or 1,25(OH) 2 D 3 therapy. Free testosterone by equilibrium dialysis (gold standard) or; Total testosterone after organic solvent extraction and calculation of free testosterone (laws of mass action equations) or; Total testosterone by RIA (with awareness of limitations) and calculation of free testosterone or; Total testosterone and calculation of free androgen index: total testosterone nM/SHBG nM×100 (if SHBG in normal range), Early morning cortisol (if adrenal insufficiency is suspected), Copyright © 2021 Human Reproduction Update. There are currently a number of studies being undertaken in this area. Similarly, girls may fail to start their periods and may not undergo many of the changes usually seen in puberty. Doctors may have difficulty detecting low testosterone levels in … In a recent study of 147 women, calculated free T was found to correlate well with free T measured by equilibrium dialysis (r = 0.99; P<0.0001). DHEAS is secreted solely by the adrenals. Investigate and diagnose the cause of male physical characteristics (virilization) in young girls and … However, not all women will experience a decline in androgen levels that translates into the clinical symptoms of FAI. L.M. Furthermore, whether depression can be a consequence of, or a cause of, androgen insufficiency remains unclear and requires further study for clarification. As the existence of the condition ‘androgen deficiency in women’ is still under debate, there is no standard treatment, and no licensed or registered treatment is available for women in Australia. Results of testosterone levels can only be interpreted in light of these limitations. There have been no long-term studies of testosterone therapy in women, so the long-term health risks and benefits are unknown. For example, the amount circulating in the blood does not reflect the amount active inside body cells. This is an area of androgen physiology that requires further investigation. Davis et al. There are currently various testosterone transdermal patches (Shifren et al., 2000), a 1% testosterone cream (Goldstat et al., 2003), transdermal sprays, patches, creams and gels along with intranasal sprays in development in large-scale clinical trials. However, the risk associated with exposure to exogenous testosterone in postmenopausal women is unclear, as these studies had various methodological limitations. It is an active hormone with effects similar to … Few studies have been done examining testosterone use in premenopausal women, as there is a risk that testosterone could harm a developing baby and result in the need for termination of pregnancy. Moreover, salivary testosterone levels should not be equated to levels of free testosterone in serum. Clinical symptoms along with testosterone levels are used to monitor therapy (Table III). Testosterone levels lower than 20 ng/dL in women aged 50 and older are considered low. Intranasal estradiol does not increase SHBG significantly (Mattson et al., 2000). As such, when investigating for androgen insufficiency, measures of total testosterone along with SHBG are required. In contrast to the androgen levels, the median SHBG levels increased steadily in men from 20.8 to 44.5 nmol/l, while the median SHBG levels in women decreased from 78.3 to 44.5 nmol/l in the age group of 61-70 years. While drugs and diet are clearly potential causes of low T in women, simply being obese or chronically avoiding exercise might also cause low levels. Dehydroepiandrosterone, 50 mg/d, increases DHEAS levels. Arthritis & Rheumatism. What is the Androstenedione Blood Test? 25.6). This web site is managed and authorised by the Department of Health, State Government of Victoria, Australia © Copyright State of Victoria 2020. Sex steroid-hormone binding globulin (SHBG) is a major determinant of the bioavailability of sex steroids. It appears that total and free testosterone levels decline with age in premenopausal women from the early to mid reproductive years (Zumoff et al., 1995), remain stable across the menopausal transition (Burger et al., 2000) and then either remain stable, continue to decline or increase with increasing age.
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