Randomized placebo‐controlled trial of testosterone replacement in men with mild Leydig cell insufficiency following cytotoxic chemotherapy

Howell, Simon; Radford, John; Adams, Judith E.; Smets, E. M. A.; Warburton, Rod R.; Shalet, Stephen M

doi:10.1046/j.1365-2265.2001.01297.x

Cited by 104 publications

(54 citation statements)

References 49 publications

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“…The frequently prescribed 5α-reductase inhibitors for prostate enlargement can induce mild hypogonadal symptoms [Thompson et al 2003]. Many cancer treatments, such as alkylating agents, can significantly harm Leydig-cell function and spermatogenesis [Howell et al 2001]. Systemic glucocorticoids have direct inhibitory effects on all levels of the HPG axis, which can persist up to 12 months after cessation of therapy [Morrison et al 1994].…”

Section: Etiologies Of Hypogonadism In Aging Menmentioning

confidence: 99%

Testosterone deficiency in the aging male

McBride

Carson

Coward

2015

Therapeutic Advances in Urology

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Treatment for hypogonadism is on the rise, particularly in the aging population. Yet treatment in this population represents a unique challenge to clinicians. The physiology of normal aging is complex and often shares the same, often vague, symptoms of hypogonadism. In older men, a highly prevalent burden of comorbid medical conditions and polypharmacy complicates the differentiation of signs and symptoms of hypogonadism from those of normal aging, yet this differentiation is essential to the diagnosis of hypogonadism. Even in older patients with unequivocally symptomatic hypogonadism, the clinician must navigate the potential benefits and risks of treatment that are not clearly defined in older men. More recently, a greater awareness of the potential risks associated with treatment in older men, particularly in regard to cardiovascular risk and mortality, have been appreciated with recent changes in the US Food and Drug Administration recommendations for use of testosterone in aging men. The aim of this review is to provide a framework for the clinician evaluating testosterone deficiency in older men in order to identify correctly and treat clinically significant hypogonadism in this unique population while minimizing treatment-associated harm.

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Section: Etiologies Of Hypogonadism In Aging Menmentioning

confidence: 99%

Testosterone deficiency in the aging male

McBride

Carson

Coward

2015

Therapeutic Advances in Urology

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“…[24][25][26] Similarly, merely replacing testosterone does not restore sexual function and satisfaction among men with abnormal hormonal profiles after bone marrow transplantation. 27 Sexual rehabilitation after cancer in women also cannot be reduced to a simple paradigm of hormonal replacement or a mechanical device. Despite promising results with using testosterone patches to treat low desire, 20 female cancer survivors have to consider their risk for breast cancer that may be potentiated by such therapy.…”

Section: Sexual Rehabilitation After Cancer Treatmentmentioning

confidence: 99%

Sexuality and Fertility after Cancer

Schover¹

2005

Hematology

164

124

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As more people achieve long-term survival after cancer, sexual dysfunction and infertility have increasingly been recognized as negative consequences that impact quality of life. Sexual dysfunction is a frequent long-term side effect of cancer treatment, but damage to different underlying physiological systems is salient in men versus women. Men frequently have erectile dysfunction (ED) related to damage to the autonomic nervous system and/or reduced circulation of blood to the penis. Hormonal impairment of sexual function is less common. Women, in contrast, are able to overcome damage to autonomic nerves if genital tissues remain structurally intact and estrogenized. Female sexual dysfunction is frequently associated with sudden premature ovarian failure or direct effects of radiation fibrosis or scar tissue causing pain with sexual activity. The lack of validated interventions for sexual rehabilitation after cancer is a major problem, as is finding cost-effective ways of providing services. Concerns about fertility are also a major source of distress to people treated for cancer during childhood or young adulthood, yet many young survivors do not recall any discussion about future childbearing potential with their oncology team. Since fertility preservation is becoming more practical for both men and women, producing patient and professional educational materials and developing professional practice guidelines should be high priorities for oncology societies.As long as cancer treatments cannot be exclusively targeted to tumor cells, damage to the reproductive system will remain an important aspect of cancer morbidity. Problems with sexual function and fertility after cancer are not only ubiquitous, they are less likely to resolve with time than most other treatment side effects. Although not every cancer survivor cares about remaining sexually active, longterm sexual dysfunction has been documented in at least 50% of those treated for breast, prostate, colorectal or gynecological cancer.1 Most available information about sexual dysfunction and fertility is from patients treated for solid tumors. Distress about cancer-related infertility is typically highest among those diagnosed in their reproductive years. Although a much smaller percentage of people treated for cancer are affected by infertility than by sexual dysfunction, 1 in 71 men and 1 in 51 women are diagnosed with a malignancy before age 39.2 Although some cancer treatments can cause both sexual dysfunction and infertility, these two types of morbidity are frequently independent. For example, many young men treated with chemotherapy have poor semen quality, but with all but the highdose regimens, their testosterone levels and sexual function remain normal.3 Therefore, sexual function and fertility will be discussed in separate sections. Sexual Function, Gender, and Damage from Cancer TreatmentThe most common sexual problems after cancer treatment include loss of desire for sex in men or women, erectile dysfunction (ED) in men, and pain with sexual act...

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“…The one study in younger adults examined a group of men with mild hypogonadism following treatment with gonadotoxic chemotherapy for cancer [55]. This study by our group differed from previous reports in that the definition of mild testosterone deficiency was based on both the luteinizing hormone (LH) level and the testosterone level, on the assumption that minor reductions in testosterone production would result in reduced hypothalamicpituitary negative feedback and therefore a rise in LH levels.…”

Section: Who To Treatmentioning

confidence: 46%

“…We demonstrated significantly lower femoral neck BMD, subtle changes in body composition and some reductions in sexual function in the study cohort compared with a control group of men who had undergone the same treatment for the same malignancies but had entirely normal LH and testosterone levels. However, testosterone replacement in these men did not result in any significant improvement in BMD, body composition, energy levels, mood or sexual function, and we concluded that androgen replacement could not be recommended for men with the mild biochemical abnormalities observed in this cohort [55]. Thus, whilst there is good evidence for the benefits of testosterone replacement in men with a total testosterone !7 nmol/l (200 ng/dl), the role of androgen replacement in milder degrees of androgen deficiency is less clear.…”

Section: Who To Treatmentioning

confidence: 71%

Testosterone Deficiency and Replacement

Howell

Shalet²

2001

Horm Res Paediatr

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In the human male, testosterone is the major circulating androgen. More than 95% of circulating testosterone is secreted by the testis with a production rate of 6–7 mg/day. The clinical effects of androgens are numerous, and testosterone deficiency is associated with a number of clinical abnormalities. Overt hypogonadism results in reductions in bone mineral density, alterations in body composition and effects on mood, aggressive behaviour, cognitive function, sexual function and several factors important for cardiovascular risk. Androgen replacement in this context is clearly beneficial, and numerous studies have demonstrated improvements in bone and muscle mass, reductions in body fat, and positive effects on quality of life following treatment. The benefits of therapy in men with milder degrees of hypogonadism, and elderly men with ‘physiological’ testosterone deficiency, are less clear-cut, and the appropriate biochemical cut-off below which replacement should be offered has not been clearly defined. Several options are available for androgen replacement in adult men. Oral testosterone, intramuscular injections, subcutaneous implants and transdermal therapy have all been used. Each mode of delivery has advantages and drawbacks and the choice between them will often depend on patient reference. Recent advances include the development of longer-acting intramuscular preparations, which offer more stable androgen levels with fairly infrequent injections, and testosterone gel which appears to provide transdermal replacement without a high incidence of skin reactions. This article will examine the evidence concerning the impact of male hypogonadism and the response to androgen therapy. The question of who to treat will be addressed with particular reference to mild hypogonadism and hypogonadism in the elderly. Finally, an overview of the different modes of replacement therapy will be presented.

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Randomized placebo‐controlled trial of testosterone replacement in men with mild Leydig cell insufficiency following cytotoxic chemotherapy

Cited by 104 publications

References 49 publications

Testosterone deficiency in the aging male

Testosterone deficiency in the aging male

Sexuality and Fertility after Cancer

Testosterone Deficiency and Replacement

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