Testosterone in women

Herold DA, Fitzgerald RL. 2003. Immunoassays for testosterone in women better than a Guess Clin Chem 49 1250-1251. 

Testosterone assays have been notoriously inaccurate, particularly at the low levels found in women and children. Excess testosterone in women is often a cause of infertility, hirsutism, amenorrhea, and obesity, and accurate measurement is essential... 

Oxime derivatization was utilized by Kushnir et al. [44] to improve ESI sensitivity for testosterone measurement. Using a C18 column for separation (3-min run times) and an API 4000 they monitored MRM transitions 304—>124 and 112 for testosterone oxime and 307—>14 and 112 for the d3 internal standard. Within-run and between-run irreproducibility was < 12%. The LOD was 10 pg/ml, allowing accurate measurement of testosterone in women and children. Reference intervals for the steroid in children of different ages and different Tanner stages are given in the publication as well as values for both free and total testosterone. 

Salivary testosterone concentration correlates with free testosterone concentrations in plasma and has been advocated as an indicator of androgen status. In a multicenter evaluation that examined nine different laboratories using various RIA methods with and without extraction, good correlation was found between laboratories despite widely varying methods. Reference intervals of 4 to 14ng/dL and 2 to 6ng/dL have been reported for testosterone in saliva of men. Measurement of salivary testosterone in women has been less reliable, with no consensus on salivary concentrations available. However, one commer-... 

The differentiation of normal from abnormal concentrations of plasma testosterone in women requires the use of either electron-capture GLC, isotopic-displacement methods, double-isotope methods, or fluorometric methods. Evidence to date suggests that the isotopic-displacement method is preferable (K3, M3). Existing fluorometric methods are adequate in analytical characteristics, but much more laborious (F2). This differentiation is crucial in cases of simple, provisionally idiopathic, hirsutism (cf. however. Cl). In many cases, however, an elevated excretion of urinary testosterone glucuronide would be equally satisfactory despite the uncertainty of its metabolic precursors (B2, II). This measurement is also desirable in cases of provisionally idiopathic amenorrhea. 

Dehydroepiandrosterone and androstenedione are the principal androgens. They have little masculinizing effects in men, but are metabolized to testosterone in women, resulting in development of pubic hair and libido. 

LH-RH (Luteinizing Hormone-Releasing Hormone) agonists are drugs that inhibit the secretion of sex hormones. In men, LH-RH agonists cause testosterone levels to fall. In women, LH-RH agonists cause the levels of estrogen and other sex hormones to fall. 

The advantage of this division of labour is not obvious but one possibility is that secretion of testosterone by the cells not only provides a precursor for oestradiol but provides a hormone that is secreted into the bloodstream to influence, perhaps surprisingly, sexual activity in women, particularly sexual arousal and interest. 

Steroid hormones These are the oestrogens (mainly oestradiol in women) progesterone, testosterone and 5a-dihydrotestosterone. 

The nonapeptide leuprolide is a synthetic analog of the decapeptide, gonadotropin releasing hormone, and it exceeds the activity of the natural hormone and significantly elevates the level of testosterone and dihydrotestosterone in men, and estrogen in women. It also inhibits foUicle-stimulating hormone and leutenizing hormone. 

Pharmacology Testosterone, produced by the Leydig cells of the testis, is the primary natural androgen. In women, small amounts are synthesized by the ovary and adrenal cortex. 

Testolactone is a synthetic drug related to testosterone. It is used for palliative treatment of advanced breast cancer in postmenopausal women and in women who have had their ovaries removed. The principal action of testolactone is reported to be inhibition of steroid aromatase activity and the reduction in estrone synthesis. The most common adverse effects are nausea, vomiting, and anorexia. An advantage is that it does not cause women to develop male characteristics such as a deep voice or facial hair. 

At high doses, ketoconazole causes a clinically significant reduction in testosterone synthesis and blocks the adrenal response to corticotropin. Gynecomastia, impotence, reduced sperm counts, and dimiiushed libido can occur in men, and prolonged drug use can result in irregular menses in women. These hormonal effects have led to the use of ketoconazole as a potential adjunctive treatment for prostatic carcinoma. 

Human prolactin is similar in structure to human growth hormone, and both are good lactogens. In women, prolactin acts with other hormones on the mammary gland during pregnancy to develop lactation and after birth to maintain it. Hyperprolactinemia causes impotence in men and amenorrhea and infertility in women. Chronically elevated levels of circulating prolactin are associated with suppression of 17-p-estradiol and testosterone production in the ovaries and testes. 

Concentrations of plasma testosterone and other androgens vary throughout the day in both sexes whether such variation is simply random or fits a repeatable diurnal pattern is a matter of debate. Compared with the diurnal variation seen with cortisol, plasma testosterone concentrations are reasonably constant. Plasma androgen concentrations also vary greatly in women through the menstrual cycle, with peak levels seen in the luteal phase. 

In men, approximately 8 mg of testosterone is produced daily. About 95% is produced by the Leydig cells and only 5% by the adrenals. The testis also secretes small amounts of another potent androgen, dihydrotestosterone, as well as androstenedione and dehydroepiandrosterone, which are weak androgens. Pregnenolone and progesterone and their 17-hydroxylated derivatives are also released in small amounts. Plasma levels of testosterone in males are about 0.6 mcg/dL after puberty and appear to decline after age 50. Testosterone is also present in the plasma of women in concentrations of approximately 0.03 mcg/dL and is derived in approximately equal parts from the ovaries and adrenals and by the peripheral conversion of other hormones. 

Spironolactone, a competitive inhibitor of aldosterone (see Chapter 15), also competes with dihydrotestosterone for the androgen receptors in target tissues. It also reduces 17a-hydroxylase activity, lowering plasma levels of testosterone and androstenedione. It is used in dosages of 50-200 mg/d in the treatment of hirsutism in women and appears to be as effective as finasteride, flutamide, or cyproterone in this condition. 

Other uses of the reproductive hormone approach are to avoid cyclical use of estrogen/progestins, eliminate progestins, add testosterone, or add dihydroepian-drosterone (DHEA). Such approaches remain anecdotal and require controlled studies of how they may be useful augmenting agents for antidepressants both in women and in men. 

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