A physical examination is necessary when HSDD is acquired and generalized in a man. However, one might legitimately ask what to look for since HSDD can be seen as a symptom of a disorder, or, as a syndrome (i.e., as a collection of symp- toms which result from a wide variety of causes). When associated with another disease, loss of sexual desire may resemble other phenomena like loss of appetite or fatigue—symptoms linked to many different medical and psychiatric disorders ranging from depression to cancer, and not having any specific physical findings.
When no specific cause of HSDD is apparent from the history, one must then consider an unrecognized disorder (like renal, cardiac, or endocrine disease) when conducting a physical examination. The principal endocrine disorders would be hypoandrogen states and hypothyroidism. Signs of the former can be subtle and in men, are often delayed. When considering hypogo- nadism, examination of the testes is mandatory. “Since generalized disease and
endocrine disorders can coexist, the presence of the former does not necessarily mean that the explanation for sexual desire loss has been found and that a search for an accompanying endocrine disorder, is, therefore, unnecessary.” (12; p. 180).
A labaratory exam is only warranted when the sexual desire problem is clearly generalized. When a lab exam is required, the following should be considered:
1. Testosterone (T): (see section on “Hormones” in this chapter).
2. Prolactin (PRL): When an abnormal value is detected, it is best to repeat the test at least once and preferably twice since errors are common. When PRL is high, the T level is also often abnormal. More elaborate assessment of an abnormal PRL level involves brain imaging [magnetic resonance imaging (MRI) or computerized tom- ography (CT)], visual fields, and pituitary function tests. Patients who have repeatedly abnormal PRL levels, who require more elaborate testing, and where the etiology is not apparent, should be referred to an endocrinologist. Values which are higher than normal infrequently occur in a healthy man. When the PRL level is abnormal, one of the most common pathological causes is the use of an antipsychotic medi- cation. An unusual but serious cause is a prolactin-secreting tumor.
3. Erectile dysfunction (ED) often occurs together with sexual disinterest and it may not be easy to establish which preceded the other. Under such circumstances, it is wise to investigate common causes of ED by ensuring that the patient does not have diabetes (obtaining a fasting blood sugar), or elevated lipids [assessing his total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), and triglycerides], or abnormal thyroid function [investigating his thyroid stimulating hormone (TSH)].
Two hormones influence sexual desire in men: androgens generally—of which the most consequential is T, and PRL.
Components and Measurement (21)
There are three kinds of T: (i) free, that is, not bound to any protein (FT), (ii) bound to albumin, and (iii) bound to sex hormone binding globulin (SHBG). Only 2% of T is in the free form; about 60% of the remainder is weakly bound to albumin and other proteins; and about 40% is bound with a higher binding affinity to SHBG (Fig. 4.2).
Figure 4.2 Testosterone partitions in the serum. [Reprinted with permission from (Testosterone and Aging: Clinical Research Directions) (2004) by the National Academy of Sciences, courtesy of the National Academies Press, Washington, D.C.]
Total T comprises FT with whatever is bound to protein. The part that is most easily available to tissues is referred to as bioavailable testosterone (BAT) and includes both FT and the portion that is bound to albumin.
Total T is measured by radioimmunoassay which is a validated, standar- dized, and reproducible assay. However, as SHBG increases with age, and therefore a greater percentage of the total T is bound to SHBG, this measure may not be so informative in older men. BAT is measured in several ways including separately calculating the total T and SHBG. Measurement of FT is more difficult and “controversial” (21; p.18).
Segraves and Balon estimate that 200 – 350 ng/dL of T is required for normal sexual function and that above 450 ng/dL, “it is difficult to demonstrate a relationship between testosterone and sexual activity.” (22; p. 216).
Measurement of T is best performed in the morning because of the diurnal variation in blood levels.
Normal Aging Changes in the Quantity
In adult men, T increases greatly from 0.2 to 0.7 nmol/L (50 – 20 ng/dL) to the normal adult male level of 10 – 35 nmol/L ( 300 – 1000 mg/dL) by about age 17. The level of BAT (see later) remains balanced until men are in their 30s or 40s and then decreases slowly over the remainder of the man’s life at a rate of about 1.2% per year. (The latter contrasts with women who experience a sudden drop in estrogen and progesterone when ovulation ends.) In healthy
men, mean serum T levels decrease by 30% between ages 25 and 75. Mean FT levels decrease by as much as 50% over the same period. The steeper decline of FT is explained by the age-associated increase in SHBG. “At any age, the range of values observed, both for T and FT, is very wide … it is evident that … the limits of normality are rather arbitrary and that the sensitivity threshold for androgens might vary from tissue to tissue and possibly, also according to age” (23).
In addition to T, many hormones gradually change in the aging male including growth hormone (GH) and adrenal compounds [dehydroepiandroster- one (DHEA) and its sulfate (DHEAS)].
Origin, Production, and Control
Testosterone in men derives mostly from the testis but a small amount comes from the adrenal cortex. Hormonal control over the production of testicular T begins in the hypothalamus, which secretes gonadotropin-releasing hormone (GnRH) (Fig. 4.3). GnRH, in turn, stimulates the anterior part of the pituitary gland to produce both leutinizing hormone (LH) and follicle stimulating
Figure 4.3 Regulation of testosterone and sperm production by LH and FSH. (C ¼ cholesterol, T ¼ testosterone). Source: Griffin JE, Wilson JD. Disorders of the testes. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles of Internal Medicine. 15th ed. New York: McGraw-Hill, 2001:2143. (Reprinted with permission.)
hormone (FSH) both of which act on cells in the testes. LH causes the Leydig cells to produce T and FSH induces the Sertoli cells to produce spermatozoa. A negative feedback mechanism results in the testes controlling the output of LH and FSH. In older men, the function of both the testes and the hypothala- mic-pituitary axis are diminished and for both reasons, the output of T is less (24).
About 5 – 6 mg of T is secreted daily into the plasma of men, usually in a pulsatile manner every 60 – 90 min, and in a diurnal rhythm in which peak levels occur during the morning (although less pronounced in older men) (25). In addition to intraday fluctuations, there is a wide range of normal levels between different individuals.
Testosterone can act either (a) directly on target cells or (b) indirectly by being converted first to its principal metabolites, dihydrotestosterone (DHT), and estra- diol. Although both T and DHT bind to the androgen receptor, the latter does so more strongly and is therefore more potent. Two enzymes convert T to its metab- olites: 5 alpha-reductase, which converts T to DHT and which is found especially in prostate, skin, and reproductive tissues, and aromatase which converts T to estradiol and is found especially in adipose tissue, liver, and some central nervous system nuclei. Thus, the actions of T are widespread throughout the body.