Testosterone replacement therapy-perceptions of recipients and partners

Background. The androgenic hormones are important determinants of sexual behaviour in men. Testosterone replacement is important treatment for pituitary disease to maintain normal functioning. Although the physical effects of testosterone replacement have been well documented, little is known about the effects on relationships, particularly from the point of view of the sexual partners of men receiving testosterone replacement.

Aims. This paper reports a study exploring the perceptions of testosterone replacement on well-being and sexual functioning.

Methods. Semi-structured interviews were conducted with five men receiving testosterone implants (recipients), their permanent partners, and five recipients without partners. Recipient serum testosterone concentration was measured at 0, 1 and 4 months after testosterone implantation.

Results. The three groups reported similar effects of testosterone on well-being and sexual functioning. Recipient and partner ratings were also similar. Strength was less affected by decreasing testosterone concentration than energy in men with partners, but both strength and energy declined in men without partners. Decreased testosterone levels had a statistically significantly different effect on libido at time zero between men with and without partners (P < 0·015) and on ability to sustain an erection, but the ability to achieve an erection persisted over the 6 months in both male groups. Intercourse frequency increased from once per week at time 0 to ≥3 per week between 1 and 4 months after implant in men with partners. There were important effects of testosterone deficiency on general and sexual relationships, and these differed between men with partners and those without.

Conclusions. Testosterone has important physical and psychological benefits that may be related to the age at which testosterone replacement commences and the indications for its use. The small sample size may limit the ability to generalize the findings outside the study.

Hormone replacement therapy and cardiovascular disease

The authors examine the most recent research concerning the risks and benefits of oestrogen or combined oestrogen-progestin therapy in postmenopausal women.

Acute delirium in the setting of primary hypothyroidism: the role of thyroid hormone replacement therapy.

Psychiatric illness, mostly mania and psychosis, are reported to occur after rapid normalization of thyroid function in patients with primary hypothyroidism. It is generally believed that the gradual restoration of thyroid function may reduce the risk of psychiatric complications. This case report describes the occurrence of acute delirium in a 67-year-old man with primary hypothyroidism shortly after the initiation of thyroid hormone replacement. The use of low-dose thyroxine initially and persistent severe biochemical hypothyroidism on presentation with psychiatric symptoms illustrate that psychiatric illness can still occur despite unaggressive thyroid hormone replacement. A temporal relationship with the initiation of thyroxine and rapid recovery of mental state over 1 to 2 weeks differentiate this condition from hypothyroidism-related psychopathology, which tends to have a more prolonged course.

Hormone therapy is associated with smaller achilles tendon diameter in active post-menopausal women

The effects of hormonal status and activity levels on Achilles tendon structure were examined in asymptomatic post-menopausal women. It was hypothesized that women using hormone replacement therapy (HRT) would have better tendon structure than those not using HRT and that active women would have poorer tendon structure than inactive women. Eighty-five women including 53 active women (regular golf players) and 32 controls (healthy but inactive women) recorded their HRT and menopausal history and underwent basic anthropometric measurements. Women were divided into two groups based on their hormonal status: those currently using HRT; and those who had never used HRT or ceased using HRT at least 12 months prior to the study. Achilles tendons were examined with ultrasound and categorized as normal or abnormal, and the diameter of each tendon (mm) was recorded. Active women had a greater prevalence of tendon abnormality ( P=0.10) and thicker Achilles tendons than inactive women ( P<0.05). Active women on HRT had less tendon abnormality ( P=0.056) than active women not on HRT and significantly less tendon thickness ( P<0.05). This study indicates that Achilles tendon diameter is greater in active post-menopausal women. Hormone replacement therapy appeared to ameliorate this effect in active women. A similar effect from HRT on the Achilles tendons of inactive women was not apparent.

The effectiveness of personalized smoking cessation strategies for callers to a Quitline service

Aim To assess the effectiveness of a program of computer-generated tailored advice for callers to a telephone helpline, and to assess whether it enhanced a series of callback telephone counselling sessions in aiding smoking cessation.

Design Randomized controlled trial comparing: (1) untailored self-help materials; (2) computer-generated tailored advice only, and (3) computer-generated tailored advice plus callback telephone counselling. Assessment surveys were conducted at baseline, 3, 6 and 12 months.

Setting Victoria, Australia.

Participants A total of 1578 smokers who called the Quitline service and agreed to participate.

Measurements Smoking status at follow-up; duration of cessation, if quit; use of nicotine replacement therapy; and extent of participation in the callback service.

Findings At the 3-month follow-up, significantly more (χ2(2) = 16.9; P < 0.001) participants in the computer-generated tailored advice plus telephone counselling condition were not smoking (21%) than in either the computer-generated advice only (12%) or the control condition (12%). Proportions reporting not smoking at the 12-month follow-up were 26%, 23% and 22%, respectively (NS) for point prevalence, and for 9 months sustained abstinence; 8.2, 6.0, and 5.0 (NS). In the telephone counselling group, those receiving callbacks were more likely than those who did not to have sustained abstinence at 12 months (10.2 compared with 4.0, P < 0.05). Logistic regression on 3-month data showed significant independent effects on cessation of telephone counselling and use of NRT, but not of computer-generated tailored advice.

Conclusion Computer-generated tailored advice did not enhance telephone counselling, nor have any independent effect on cessation. This may be due to poor timing of the computer-generated tailored advice and poor integration of the two modes of advice.

Metabolism and transport of oxazphosphorines and the clinical implications

The oxazaphosphorines including cyclophosphamide (CPA), ifosfamide (IFO), and trofosfamide represent an important group of therapeutic agents due to their substantial antitumor and immuno-modulating activity. CPA is widely used as an anticancer drug, an immunosuppressant, and for the mobilization of hematopoetic progenitor cells from the bone marrow into peripheral blood prior to bone marrow transplantation for aplastic anemia, leukemia, and other malignancies. New oxazaphosphorines derivatives have been developed in an attempt to improve selectivity and response with reduced toxicity. These derivatives include mafosfamide (NSC 345842), glufosfamide (D19575, β-D-glucosylisophosphoramide mustard), NSC 612567 (aldophosphamide perhydrothiazine), and NSC 613060 (aldophosphamide thiazolidine). This review highlights the metabolism and transport of these oxazaphosphorines (mainly CPA and IFO, as these two oxazaphosphorine drugs are the most widely used alkylating agents) and the clinical implications. Both CPA and IFO are prodrugs that require activation by hepatic cytochrome P450 (CYP)-catalyzed 4-hydroxylation, yielding cytotoxic nitrogen mustards capable of reacting with DNA molecules to form crosslinks and lead to cell apoptosis and/or necrosis. Such prodrug activation can be enhanced within tumor cells by the CYP-based gene directed-enzyme prodrug therapy (GDEPT) approach. However, those newly synthesized oxazaphosphorine derivatives such as glufosfamide, NSC 612567 and NSC 613060, do not need hepatic activation. They are activated through other enzymatic and/or non-enzymatic pathways. For example, both NSC 612567 and NSC 613060 can be activated by plain phosphodiesterase (PDEs) in plasma and other tissues or by the high-affinity nuclear 3'-5' exonucleases associated with DNA polymerases, such as DNA polymerases and ε. The alternative CYP-catalyzed inactivation pathway by N-dechloroethylation generates the neurotoxic and nephrotoxic byproduct chloroacetaldehyde (CAA). Various aldehyde dehydrogenases (ALDHs) and glutathione S-transferases (GSTs) are involved in the detoxification of oxazaphosphorine metabolites. The metabolism of oxazaphosphorines is auto-inducible, with the activation of the orphan nuclear receptor pregnane X receptor (PXR) being the major mechanism. Oxazaphosphorine metabolism is affected by a number of factors associated with the drugs (e.g., dosage, route of administration, chirality, and drug combination) and patients (e.g., age, gender, renal and hepatic function). Several drug transporters, such as breast cancer resistance protein (BCRP), multidrug resistance associated proteins (MRP1, MRP2, and MRP4) are involved in the active uptake and efflux of parental oxazaphosphorines, their cytotoxic mustards and conjugates in hepatocytes and tumor cells. Oxazaphosphorine metabolism and transport have a major impact on pharmacokinetic variability, pharmacokinetic-pharmacodynamic relationship, toxicity, resistance, and drug interactions since the drug-metabolizing enzymes and drug transporters involved are key determinants of the pharmacokinetics and pharmacodynamics of oxazaphosphorines. A better understanding of the factors that affect the metabolism and transport of oxazaphosphorines is important for their optional use in cancer chemotherapy.

Guidelines for treatment of osteoporosis in men

BACKGROUND: Osteoporosis is associated with significant morbidity and mortality in men. Published randomised controlled trials assessing the benefits of therapy in men with osteoporosis are limited, but those available need to be used to develop management guidelines.

OBJECTIVE: To present evidence based guidelines for the treatment of osteoporosis in men.

DISCUSSION: It is estimated that 30-60% of men presenting with spinal fractures have another illness contributing to their bone disease. Therefore assessment and treatment of coexisting medical conditions is a vital part of management of osteoporosis. While primary prevention of fractures remains crucial, treatment to ensure further fractures do not occur is equally important. Alendronate is the treatment of choice for men with osteoporosis and fractures, with cyclical etidronate an appropriate alternative and testosterone replacement therapy is indicated in hypogonadal men presenting with osteoporosis.

Lesbians' experience of menopause

This thesis examines the menopausal experiences of a non-clinical sample of lesbians living in Australia. Research on menopause to date has largely been conducted from a medicalised and heterosexual perspective: thus lesbians’ experiences remain unknown and invisible. Using a qualitative feminist multiple method research methodology combining content analysis and questionnaire/interview research, two hundred questionnaires were posted upon request to self-identified lesbians living in every Australian state and territory. Follow up in-depth interviews were conducted with twenty lesbians. Responses were grouped into four major themes: body image, sex and sexuality, hormone replacement therapy and health services and homophobia. The findings show that lesbians at menopause face some different and additional issues from those experienced by heterosexual midlife women. For many of the study participants, commonly discussed concerns at menopause such as weight gain and other physical signs of ageing, decreased fertility, lack of libido, sexual difficulties and hormone replacement therapy were of little relevance and importance. Lesbians in this study frequently raised other issues such as the universal assumption of heterosexuality and homophobia experienced when interacting with health professionals, which led to less than satisfactory health care and reinforced feelings of invisibility. In the Conclusion I argue that the study participants' views and experiences challenge negative, stereotypical views of both lesbians and menopause. The data thus add a new dimension to the presently narrow, heterosexist and medicalised view of women at midlife and contribute new knowledge to the body of literature on menopause. This thesis is a first important step in recording the experiences of lesbians regarding menopause in Australia. I include recommendations for further research in the area of lesbian health and improved practice, and discuss old and new obstacles lesbians face in a heteropatriarchal society in which lesbians continue to be invisible.

The effects of treating male hypogonadism on couples' sexual desire and function

Introduction: Hypogonadism is a common endocrine condition characterized by low levels of testosterone (T) and marked by numerous symptoms, one of which is low sexual desire. Studies comparing T delivery systems have suggested that hypogonadal men’s partners may be at risk from exposure to T gels. Little other mention is found of the impact of hypogonadism and its treatment on a man’s partner and the couple’s sexual function.

Aim: To assess sexual desire and sexual function in hypogonadal men and their woman partners before and after treatment with T replacement therapy.

Methods: Twenty-one hypogonadal men and 18 partners were recruited from a   tertiary endocrine clinic, and were compared with a control group of 20 eugonadal age-matched men and their partners. All men had baseline blood tests to confirm their status as hypogonadal or eugonadal, and hypogonadal men repeated tests at 3-month intervals. All participants completed the Sexual Desire Inventory (SDI) and sexual function questionnaires at baseline and at 3-month intervals until the hypogonadal men attained normal T levels.

Main Outcome Measures: Pre- and post-treatment SDI and sexual function questionnaires were compared once T normalization was achieved. Between- and within-group comparisons were carried out.

Results: Pretreatment hypogonadal men recorded lower levels of sexual desire and function than controls, but significantly improved once hypogonadism was corrected. Eugonadal controls recorded no significant changes in either sexual desire or function during the study. Partners of the hypogonadal men reported no changes on the SDI, but significant improvements in sexual function as their partners recovered.

Conclusion: SDI and sexual function measures reflect sexual changes that  accompany rising serum T levels during correction of male hypogonadism. Women partners reported more satisfaction, less pain, and improved sexual function following the men’s treatment. Treatments affecting one partner potentially have important effects on the other.

Dialysing acutely ill patients : the lived experience of renal nurses

This interpretive study is based on Heideggarian phenomenology and explores the lived experiences of four registered nurses experienced in the use of haemodialysis as a renal replacement therapy.

Diet high in monounsaturated fat does not have a different effect on arterial elasticity than a low-fat, high-carbohydrate diet

Objective : To compare the effects of a modified-fat diet high in monounsaturated fat, and a low-fat/high-carbohydrate diet on arterial elasticity.
Design : Randomized crossover design; each diet period was 1 month and a 2-week wash out period occurred in between.
Subjects/setting : Thirty healthy, free-living, nonsmoking men and women were recruited from the Melbourne, Australia, metropolitan region of Australia. Men were aged 35 to 55 years and postmenopausal women were aged 50 to 60 years and were not taking hormone replacement therapy. Twenty-eight subjects completed the study.
Intervention : Two diets of equal energy value: a modified-fat diet and a low-fat/high-carbohydrate diet; the modified-fat diet had 3 times more energy from monounsaturated fat.
Main outcome measures : Arterial elasticity and serum lipoprotein concentrations.
Statistical analysis : The general linear model was used to investigate overall effect and any carryover or order effects. Paired t test and the general linear model were used to compare the results from the 2 diet periods.
Results : High-density lipoprotein cholesterol concentration was significantly higher on the modified-fat diet than on the low-fat/low-carbohydrate diet. Arterial elasticity and concentrations of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were not significantly different on the 2 diets.
Applications/conclusions : There is no evidence to favor a diet high in monounsaturated fat over a low-fat/high-carbohydrate diet because of an effect on arterial elasticity. Other changes in diet may be needed to cause a beneficial effect on arterial elasticity.

Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women

The possibility that the heightened cardiovascular risk associated with the menopause, which is said to be ameliorated by soybeans, can be reduced with soy isoflavones was tested in 21 women. Although several were perimenopausal, all have been included. A placebo-controlled crossover trial tested the effects of 80-mg daily isoflavones (45 mg genistein) over 5- to 10-week periods. Systemic arterial compliance (arterial elasticity), which declined with age in this group, improved 26% (P < .001) compared with placebo. Arterial pressure and plasma lipids were unaffected. The vasodilatory capacity of the microcirculation was measured in nine women; high acetylcholine-mediated dilation in the forearm vasculature was similar with active and placebo treatments. LDL oxidizability measured in vitro was unchanged. Thus, one important measure of arterial health, systemic arterial compliance, was significantly improved in perimenopausal and menopausal women taking soy isoflavones to about the same extent as is achieved with conventional hormone replacement therapy.