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Sex Chromosome Aneuploidy In The Germline

The effects of both Klinefelter and Turner syndrome's on gonad development and fertility reflect the fact that inactivated X chromosomes of XXY males are reactivated in the germ cells of the testes create, which creates an excess of X-linked genes in the testes. Similarly, in normal XX females the inactivated X is reactivated in the germ cells and oogenesis requires two active Xs. Thus, X0 females will lack the necessary second X in their oocytes. Although one X does inactivate in the germ cell progenitors of early female embryos, it is eventually reactivated in oocytes before meiosis. This reactivation reflects a stringent requirement for two X chromosomes in oogenesis. The absence of the second X chromosome in Turner syndrome females causes rapid death (atresia) of oocytes during fetal development. The result is both sterility and small rudimentary ovaries. Similarly, Klinefelter men also reactivate the second (inactivated) X chromosome in the developing testis. The presence of the...

Clinical studies of human Xlinked genes and infertility

Few studies have examined mutations in X-linked genes in male infertility patients (Table 10.4). In a study of 56 infertile men with low or no sperm counts, Raverot et al. observed mutations in the SOX3 gene (sex-determining region Y box 3) (Raverot et al., 2004). The mouse homolog of this gene is found in the developing gonad and brain and, when disrupted, causes hypogonadism with loss of germ cells. Mutations in the human fetal and adult testis-expressed (FATE) gene (Xp28) have also been studied in infertile men (Olesen et al., 2003). This gene encodes a polypeptide of 21kDa that is not related to any known proteins. The FATE message is testis specific in fetal life soon after sex-determination and is co-expressed with SRY in the 7-week-old testis. Among 144 random chosen infertile men and 100 proven fertile men, a study of the FATE gene revealed 6 nucleotide substitutions, 4 of which were not amino acid altering, and 2 mutations. Each mutation was found only once in the...

Androgen receptor gene mutations 1 60000

In this condition, the androgen receptor (AR) is absent or functionally altered such that testosterone or its more bioactive derivative, dihydrotestosterone, cannot activate target genes. Thus, androgens have little to no effect on tissues as such the development of both internal and external genitalia are affected. Depending on the severity of the AR defect, serum testosterone levels can be low, normal or high. The androgen balance in each individual depends on the functional integrity of AR within the pituitary and hypothalamus. The clinical picture of infertility is also variable (nomenclature includes Reifenstein, Lub and Rosewater syndromes) and ranges from apparent females with testes (complete androgen insensitivity) to normal but infertile males (Shkolny et al., 1999). Over 300 distinct (mainly point) mutations and have been found in the AR, a large steroid receptor gene on the X chromosome (Xq11-q12) (Bhasin et al., 1998). Given the widely variable phenotype and numerous...

Therapy Regimens for Prostate Cancer

The standard therapy for prostate cancer is medical ablative hormone therapy with GnRH analogues. Additional antiandrogenic therapy is recommended before the start of medication, as there may be a transitory increase in testosterone levels (flare-up) at the beginning of medication (orchi-ectomy is an alternative, but is usually not the therapy of first choice, for psychological reasons). Therapy can be given in 3-month or in 1-month cycles (Table 49).

The Approach Look For The Rare But Remember The Ordinary

The key to teasing out potential genetic variables in a patient's family history is to look for unusual and infrequent features against a background of common diseases and normal physical variation. Male infertility is common, but a man with infertility, small testes (hypogonadism), and absence of the sense of smell (anosmia), may have a rare inherited condition called Kallman syndrome. Diabetes mellitus is a common chronic disorder, but a person with diabetes, seizures, hearing loss, and an unsteady gait may have a mitochondrial myopathy. Males with hypogonadism and or significant gynecomastia

Klinefelter syndrome incidence 1 500

This disorder is the most common genetic cause of azoospermia, accounting for 14 of cases. It is classically associated with a triad of findings small, firm testes, azoospermia and gynecomastia. Other features of the syndrome are increased height, decreased intelligence, varicosities, obesity, diabetes, leukemia, increased likelihood of extragonadal germ cell tumors and breast cancer (20 X higher than normal). Most affected individuals, however, do not exhibit the classic clinical phenotype. This is an abnormality of chromosomal number in which 90 of men carry an extra X chromosome (47 XXY) and 10 are mosaic with a combination of XXY XY chromosomes. It is thought that approximately half of XXY cases are paternally derived and recent evidence suggests that its occurrence may correlate with advanced paternal age (Lowe et al., 2001). Testis biopsies show sclerosis and hyalinization. Hormonal evaluation usually demonstrates a low testosterone and frankly elevated luteinizing hormone (LH)...

Amyl nitrite inhalant See isobutyl nitrite

Anabolic steroids Anabolic steroids are testosterone derivatives designed to increase strength and muscle mass. Testosterone performs these functions in the body, but its masculinizing effects make it an inappropriate therapy for men who already have normal testosterone levels, or for women. The synthetic anabolic steroids, such as nandrolone, oxan-drolone, methandrostenolone, and oxymetholone, were designed to be less masculinizing than testosterone and are often used to treat men with AIDS. These men often have low testicular function or testosterone deficiencies caused by HIV suppression of normal endocrine-gland function or by drugs (like ketoconazole) used to treat opportunistic infections. These deficiencies are associated with weakness and loss of lean tissue mass. Anabolic steroids have the advantage of being dramatically cheaper than most therapies being studied for HIV-related wasting. The ability of anabolic steroids to increase muscle mass and break down fat in healthy,...

The case of the shrinking alligator penis

It was reported that the alligator population of Lake Apopka in northern Florida was declining, presumably because of lack of success in reproduction. The male animals were found to have abnormal testes, low testosterone levels, and small phalli (penises). The female alligators had abnormalities too and high levels of oestrogen. It is believed that high levels of organochlorine compounds, resulting from a spillage of the pesticide difocol, were responsible. The difocol was contaminated with DDE, a breakdown product of DDT, which may have affected the level of the sex hormones. Apparently such effects can be produced in alligators by treating them with DDE.

Single gene defects in infertile men

The number of non-Y-chromosomal human single gene defects known to impair spermatogenesis is still small (Table 9.2). Most of them are also involved in the genetic control of male gonad development or some somatic development indicating a functional linkage with the germ line. Clinically, the best known are the cystic fibrosis (CF) locus located on the long arm of chromosome 7 (7q31.2), because CF mutations were abundantly found in patients with a congenital bilateral aplasia of the vas deferens (CBAVD), that is with obstructive azoospermia (Oates and Amos, 1994). Less frequent are mutations in the androgen receptor (AR) gene which causes different pathologies, summarised under the phrase Androgen Insensitivity Syndromes (AIS Testicular feminisation, Reifenstein, Infertile male syndrome) and mutations in the genes for the Follicle-Steroid- or Luteinising hormone receptors (FSHR LHR) causing the Idiopathic Hypo- and hyper-gonadotropic Hypogonadism (IHH) syndrome and the KAL-1 gene...

The Hormonal Hypothesis

The hypothesis (known as the Geschwind-Behan-Galaburda or GBG hypothesis) generated a huge amount of research which was reviewed comprehensively by Bryden, McManus, and Bulman-Fleming (1994). It was not until 1995, however, that anyone was able to test the theory directly. Grimshaw, Bryden, and Finegan (1995) measured testosterone levels in the amniotic fluid of mothers undergoing amniocentesis at 16 gestational weeks. The levels of testosterone are assumed to reflect largely though not exclusively foetal rather than maternal levels of the hormone. The results were contrary to the predictions of the GBG hypothesis. When the children of the pregnancies which went to full term were tested at the age of 10 years, high levels of foetal testosterone were found to be associated with stronger right-handedness and stronger left lateralisation of language (measured by a non-invasive technique known as dichotic listening) than low levels of testosterone. Although there is some research linking...

Kallman syndrome 1 30000

Idiopathic hypogonadotropic hypogonadism (IHH) or Kallman syndrome is characterized by hypogonadism. Most patients experience a delay in puberty although those with less severe defects may present with only infertility. Other findings include anosmia, small testes and occasionally renal agenesis, bimanual synkinesia, cleft lip and dental agenesis. When anosmia is not present, the condition is termed IHH. Testicular biopsies display a wide range of findings from germ cell aplasia to focal areas of complete spermatogenesis (Patrizio and Broomfield, 1999). The condition is inherited as a familial disorder in one-third of cases. Both X-linked and autosomal inheritance patterns have been described (Bhasin et al., 1998 Layman et al., 1998). In the X-linked recessive form, deletions occur in Kalig-1 (kallman-interval 1 or KAL1), a gene responsible for the migration of gonadotropin releasing hormone (GnRH) neurons to the pre-optic area of the hypothalamus during development (Bick et al.,...

Examples of Evolved Psychological Mechanisms

Attractive features also serve as hormone markers, indicating higher levels of estrogen in females and testosterone in males. Research generally supports the evolutionary hypothesis that men prefer women with a low waist-to-hip ratio, an observable cue to high estrogen levels associated with greater fertility. In most studies, the ideal ratio of waist to hips is near the .7 that experts consider optimal for reproduction, but in Uganda, even larger hips attract men, probably as part of a general preference in that culture for large-bodied women (Bereczkei, 2000 Furnham, Moutafi, & Baguma, 2002). For their part, women are attracted to men whose faces show masculine bone structure features, such as a strong chin, that are produced by higher testosterone levels especially when the women respond to researchers' questions during their most fertile phase (Fink & Penton-Voak, 2002).

Testicular cancer Cancer of the testicles

Testosterone A naturally occurring male hormone, found in both men and women. Testosterone is responsible for the masculinizing and tissue-building (anabolic) changes that occur in males during adolescence, including the growth of the reproductive tract and the development of secondary sexual characteristics. When administered as a drug it can cause gain in lean body mass, increased sex drive, and possibly aggressive behavior. Many men with HIV have low testosterone levels caused by HIV suppression of normal endocrine-gland function or by drugs (like keton-conazole) used to treat opportunistic infections. These deficiencies are associated with the loss of both energy and lean tissue mass in HIV-related weight loss. Testosterone and other anabolic steroids are often prescribed as part of testosterone REPLACEMENT THERAPY. Oral and injectable testosterone have long been available to treat testosterone deficiencies. Synthetic forms are also available. The advantages of these include lower...


Sex hormones definitely affect memory this is true for men as well as women. With age, estrogen levels in women and testosterone levels in men fall, and this decline undoubtedly contributes to age-related memory loss. Many women notice problems with memory during menopause, when their estrogen levels drop dramatically. It could be that estrogen benefits memory by protecting neurons, as some laboratory studies suggest. As for men, those with high levels of testosterone in their blood have better visual and verbal memory than men with low testosterone levels, according to a large study reported by the National Institute on Aging. Low testosterone may increase the risk of memory disorders. Men with low testosterone were more likely to develop Alzheimer's disease in a study reported in the journal Neurology in 2004. The jury is still out on the benefit of testosterone supplementation in men we still don't know much about its long-term effects. A study in the Journal of Cognitive...

Endocrine factors

Endocrine disturbances can influence prevalence of the metabolic syndrome, specifically hyperandrogenaemia and polycystic ovary syndrome (PCOS) (discussed in more detail in Chapter 12). The menopause also may influence development of the metabolic syndrome and a summary of the relationships between the metabolic syndrome and menopause hormone replacement therapy (HRT) is discussed below. Also, low total testosterone and sex hormone binding globulin (SHBG) levels both independently predict development of the metabolic syndrome and diabetes in middle-aged Finnish men (Laaksonen etal., 2004). For further discussion of the role of androgens in obesity, see Marin and Arver (1998). The growth hormone-insulin-like growth factor (IGF) axis also may play a role in the development of the metabolic syndrome and this hormonal axis is discussed in more detail in Chapter 14. Similarities between Cushing's disease and the metabolic syndrome also suggest that a role for the glucocorticoid axis is...

Parental Behavior

Competition among males for reproductive opportunities makes social dominance a male issue and leads to much higher rates of aggression among males than among females, particularly among young men who are at an age when competition with other males serves the evolutionary purpose of selecting the fittest and enforcing upon women their exclusive sexual access to them (D. Jones, 1999 Mesquida & Wiener, 1996). In some studies, testosterone levels are higher, on average, in boys and men who are more aggressive (Chance, Brown, Dabbs, & Casey, 2000) and who are diagnosed with antisocial personality disorder and alcoholism (Stalenheim, Eriksson, von Knorring, & Wide, 1998). The evolutionary selection for aggression in males does not mean, however, that male aggression today is necessarily tied to competition over females. A review suggests that, more often, men are concerned with status and respect from other men (Fischer & Mosquera, 2001). Whether this means that the theorized...


Are affected by whether they were passed along by the mother or the father (Figure 23.4). Both Prader-Willi and Angelman syndrome are usually associated with newly arising deficiencies that include band q11 on chromosome 15. When that deficiency is inherited from the father, the offspring exhibits PraderWilli syndrome (obesity, small hands and feet, hypogonadism, and mental retardation). When the deficiency is inherited from the mother, the offspring exhibits Angelman (happy puppet) syndrome.


That HIV can be passed from a women to her child through breast milk. In areas where nutritionally sound alternatives are readily available, breastfeeding is discouraged for HIV-positive women. Megestrol passes through breast milk, and although it has not been shown to cause problems in nursing infants, women should consider alternatives to breast-feeding while taking the drug. Note, too, that Megestrol has been shown to decrease testosterone levels therefore, people taking the drug may want to have their testosterone levels monitored and utilize testosterone replacement therapy as appropriate.

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