Biomedical subjects

Louis J G Gooren

Publications and source records attributed to Louis J G Gooren.

At least 19 recordsLinked to original sources

PubMed2006

Calculation of bioavailable and free testosterone in men: a comparison of 5 published algorithms.

BACKGROUND: Estimation of serum concentrations of free testosterone (FT) and bioavailable testosterone (bioT) by calculation is an inexpensive and uncomplicated method. We compared results obtained with 5 different algorithms. METHODS: We used 5 different published algorithms [described by Sodergard et al. (bioTS and FTS), Vermeulen et al. (bioTV and FTV), Emadi-Konjin et al. (bioTE), Morris et al. (bioTM), and Ly et al. (FTL)] to estimate bioT and FT concentrations in samples obtained from 399 independently living men (ages 40-80 years) participating in a cross-sectional, single-center study. RESULTS: Mean bioT was highest for bioTS (10.4 nmol/L) and lowest for bioT(E) (3.87 nmol/L). Mean FT was highest for FTS (0.41 nmol/L), followed by FTV (0.35 nmol/L), and FTL (0.29 nmol/L). For bioT concentrations, the Pearson correlation coefficient was highest for the association between bioTS and bioTV (r = 0.98) and lowest between bioTM and bioTE (r = 0.66). FTL was significantly associated with both FTS (r = 0.96) and FTV (r = 0.88). The Pearson correlation coefficient for the association between FTL and bioTM almost reached 1.0. Bland-Altman analysis showed large differences between the results of different algorithms. BioTM, bioTE, bioTV, and FTL were all significantly associated with sex hormone binding globulin (SHBG) concentrations. CONCLUSION: Algorithms to calculate FT and bioT must be revalidated in the local setting, otherwise over- or underestimation of FT and bioT concentrations can occur. Additionally, confounding of the results by SHBG concentrations may be introduced.

Adult↗

PubMed2006

Effect of testosterone administration on serum and urine kallikrein concentrations in female-to-male transsexuals.

BACKGROUND: Concentrations of human tissue kallikreins (hKs), a group of 15 secreted serine proteases found in many tissues, are modulated by steroid hormones in cancer cell lines. To gain insight into in vivo kallikrein regulation we measured kallikrein concentrations in serum and urinary tissue in female-to-male transsexuals before and after testosterone administration. METHODS: We collected blood and urine samples before treatment and after 4 and 12 months from 28 female-to-male transsexuals who received 250 mg of testosterone esters intramuscularly every 2 weeks. We used ELISA assays to measure multiple kallikreins in serum and urine. RESULTS: After testosterone administration, serum testosterone concentrations increased by approximately 15-fold. Serum kallikrein concentrations increased dramatically for hK3 (prostate-specific antigen) and increased moderately for hK2, hK5, hK6, hK7, hK8, hK10, and hK11. In urine, we noted major increases for hK3 and hK2 only. For all other kallikrein concentrations, we observed no considerable changes. CONCLUSIONS: We conclude that, in serum and urine of female-to-male transsexuals after testosterone administration, hK3 (prostate-specific antigen) and to a lesser extent hK2 concentrations increase dramatically, but concentration of other kallikreins increase either moderately in serum (hK5, hK6, hK7, hK8, hK10, and hK11) or not at all in either serum (hK4, hK13, hK14) or urine (hK4, hK5, hK6, hK7, hK8, hK10, hK11, hK13, hK14).

Adolescent↗

PubMed2006

Serum and urine tissue kallikrein concentrations in male-to-female transsexuals treated with antiandrogens and estrogens.

BACKGROUND: The expression of human tissue kallikrein genes is regulated by steroid hormones, but most studies have been conducted with cancer cell lines. Our purpose was to examine serum and urinary tissue kallikrein concentration changes in male-to-female transsexuals before and after treatment with antiandrogens and estrogens. METHODS: Thirty-five male-to-female transsexuals receiving cyproterone acetate and estrogens (orally or transdermally) were included in this study. Serum and urine samples were collected before initiation of therapy and 4 and 12 months post therapy. ELISAs were used to measure multiple kallikreins in serum and urine. RESULTS: After antiandrogen and estrogen therapy, serum testosterone concentrations decreased dramatically, as did serum and urinary concentrations of human glandular kallikrein (hK2) and prostate-specific antigen (PSA; hK3). Statistically significant but relatively small changes in serum and urinary concentrations of many other kallikreins were also seen. Kallikreins in serum and urine were correlated before and after treatment. CONCLUSIONS: The concentrations of hK2 and hK3, but not of any other kallikreins, decrease dramatically after combined antiandrogen and estrogen treatment in male-to-female transsexuals. The smaller responses of the other kallikreins presumably reflect their expression in multiple tissues.

Adult↗

PubMed2006

Effects of long-term androgen administration on breast tissue of female-to-male transsexuals.

Our aim was to examine the effects of androgen administration on breast tissue histology of female-to-male transsexuals and to study the immunohistochemical expression of three human tissue kallikreins, hK3 (PSA), hK6, and hK10. We studied 23 female-to-male transsexuals who were treated with injectable testosterone for 18-24 months. We also used 10 control female breast tissues. All tissues were fixed in buffered formalin, embedded in paraffin, and examined by hematoxylin-eosin staining and immunohistochemical staining for PSA, hK6, and hK10. Females treated with androgens exhibited similar involutionary changes as those seen in breast of menopausal women, such as marked reduction of glandular tissue, involution of the lobuloalveolar structures, and prominence of fibrous connective tissue, but presence of only small amounts of fat tissue. Fibrocystic lesions were generally not observed. In immunohistochemistry, in control breast tissues, we found moderate to strong cytoplasmic immunoexpression of hK6 and hK10 in the epithelial ductal and lobuloalveolar structures, but myoepithelial cells were negative. Luminal secretions were also positive. In menopausal breast, the immunoexpression of hK6 and hK10 was weaker and focal. No control case showed immunoexpression for PSA. In female-to-male transsexuals, one case showed focal PSA cytoplasmic immunoexpression in the epithelium of moderately involuting lobules. Long-term administration of androgens in female-to-male transsexuals causes marked reduction of glandular tissue and prominence of fibrous connective tissue. These changes are similar to those observed at the end-stage of menopausal mammary involution.

Androgens↗

PubMed2006

Recent insights into androgen action on the anatomical and physiological substrate of penile erection.

Erectile response is centrally and peripherally regulated by androgens. The original insights into the mechanisms of action of androgens were that androgens particularly exert effects on libido and that erections in response to erotic stimuli were relatively androgen-independent. It was shown that sexual functions in men required androgen levels at the low end of reference values of testosterone. So it seemed that testosterone was not useful treatment for men with erectile difficulties, particularly following the advent of the phosphodiesterase type 5 (PDE5) inhibitors. However, approximately 50% of those treated with PDE5 inhibitors discontinue their treatment. A number of recent developments shed new light on testosterone treatment of erectile dysfunction (ED) in aging men. (1) A recent insight is that, in contrast to younger men, elderly men might require higher levels of testosterone for normal sexual functioning. (2) Several studies have indicated that PDE5 inhibitors are not always sufficient to restore erectile potency in men, and that testosterone improves the therapeutical response to PDE5 inhibitors considerably. (3) There is growing insight that testosterone has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological substrate of erectile capacity, reversible upon androgen replacement. The synthesis of PDE5 is upregulated by androgens, and the arterial inflow into the penis is improved by giving androgen. The above invites a re-examination of the merits of giving testosterone to aging men with ED. The beneficial effects of PDE5 inhibitors may only be optimally expressed in a eugonadal environment.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2006

The effects of the aromatase inhibitor anastrozole on bone metabolism and cardiovascular risk indices in ovariectomized, androgen-treated female-to-male transsexuals.

OBJECTIVE: Cases of men with estrogen resistance and aromatase deficiency have highlighted the effects of estrogens on bone metabolism, the cardiovascular system and biochemical variables of the metabolic syndrome. In eugonadal men, administration of an aromatase inhibitor induces a substantial elevation of LH and testosterone due to the decreased negative-feedback signal of estrogen and may thwart the interpretation of results. As there is no gonad for LH to act on, no increase of serum testosterone concentration will be seen in female-to-male transssexuals. The aim of this study was to investigate the effects of estrogen deprivation on bone metabolism and vascular parameters without the interference of counter-regulatory effects as seen in eugonadal men. DESIGN: Thirty ovariectomized female-to-male transsexuals participated in this double-blind, randomized trial. During 3 months, subjects received the aromatase inhibitor anastrozole 1 mg/day (n = 16) or a placebo (n = 14) in addition to parenteral testosterone esters (Sustanon 250 every 2 weeks). RESULTS: Serum 17beta-estradiol (E(2)) concentration fell significantly from 134.0 +/- 78.8 to 77.7 +/- 130.6 pmol/l compared with placebo (P < 0.01). LH and FSH levels rose without the rise of testosterone levels observed in eugonadal men. Within the placebo group, E(2) remained at baseline levels. Of the endpoint variables measured (bone metabolism and vascular parameters) no significant changes were observed compared with placebo, or within the anastrozole-treated group. CONCLUSIONS: These results may indicate that the negative effects of estrogen deprivation in men only become manifest when the concentration falls below the levels induced by our intervention with anastrozole (77 pmol/l). This assumption is supported by the observation in the anastrozole group that, although effects of the reduction of serum E(2) on vascular parameters could not be demonstrated in subjects as a group, there was a correlation between individual serum E(2) and several vascular parameters.

Anastrozole↗

PubMed2005

Serum levels of sex hormone-binding globulin (SHBG) are not associated with lower levels of non-SHBG-bound testosterone in male newborns and healthy adult men.

OBJECTIVE: It is generally accepted that SHBG decreases the bioavailability and activity of testosterone (T). In in vitro experiments increased levels of SHBG will be associated with decreased levels of non-SHBG bound testosterone (non-SHBG-T). However, in vivo SHBG can alter both production and clearance rates and thus plasma levels of T. DESIGN AND PATIENTS: In order to study the effect of SHBG on the levels of non-SHBG-T in vivo in the presence of an active hypothalamo-pituitary-gonadal (HPG) axis we conducted a cross sectional study in 400 healthy adult men with an age range of 40-80 years and in 106 newborn boys. MEASUREMENTS: In both groups, regression coefficients (beta) and partial correlation coefficients (r) were calculated for the relationship between SHBG and T or non-SHBG-T. Adult men were divided into age groups per decade (40-50 years, 51-60 years, 61-70 years and 71-80 years) to study possible differences in the impact of SHBG on the level of non-SHBG-T throughout ageing. RESULTS: Higher levels of SHBG were associated with higher levels of total testosterone in neonates (beta = 0.02 +/- 0.004, r = 0.44, P < 0.001) but not with non-SHBG-T (beta = -0.001 +/- 0.001, r = 0.05, P = 0.52). In adult men there was a significant age related increase in levels of SHBG and an age-related decrease of both total and non-SHBG-T. Higher SHBG was strongly associated with higher total testosterone in all age groups (beta = 0.26, 0.26, 0.26 and 0.23 for 40-50 years, 51-60 years, 61-70 years and 71-80 years, respectively, P < 0.001 for all age groups). Higher SHBG was not or only slightly associated with higher non-SHBG-T beta = 0.02 (P = 0.32), beta = 0.04 (P = 0.03), beta = 0.04 (P = 0.02) and beta = 0.02 (P = 0.16) for 40-50 years, 51-60 years, 61-70 years and 71-80 years, respectively. CONCLUSIONS: In contrast to general belief, SHBG levels barely influence levels of non-SHBG-bound testosterone both in male newborns and healthy adult men: the influence, if any, is positive. Consequently the age related increase of SHBG does not account for the age related decline in non-SHBG-T in healthy adult men.

Adult↗

PubMed2005

The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women.

OBJECTIVE: The objective of this study was to examine whether low levels of oestradiol and testosterone are associated with impaired mobility, low muscle strength and the incidence of falls in a population-based sample of older men and women. DESIGN: Cross-sectional population-based study, based on data of the Longitudinal Ageing Study Amsterdam (LASA), including 623 men and 663 women, aged 65-88 years. MEASUREMENTS: Serum levels of oestradiol, testosterone, albumin and sex hormone-binding globulin (SHBG) were measured. Physical performance, functional limitations and muscle strength were assessed, and a follow-up on falls was performed prospectively within 3 years. RESULTS: After adjustment for age, level of education, alcohol use, physical activity, chronic disease and body mass index (BMI), men in the highest quartile of the oestradiol/SHBG ratio had significantly higher physical performance scores than men in the lowest quartile (beta = 0.103). Serum levels of total testosterone were positively associated with muscle strength (beta = 0.085). Calculated bioavailable testosterone levels were positively associated with physical performance and muscle strength (beta = 0.128 and 0.109 respectively). No associations of oestradiol levels with mobility were seen in women. Levels of oestradiol and testosterone were not associated with falls. CONCLUSIONS: It can be concluded that low levels of sex hormones were associated with impaired mobility and low muscle strength in men, but not in women. Levels of sex hormones were not associated with the incidence of falls neither in men, nor in women.

Accidental Falls↗

PubMed2005

The sex difference of plasma homovanillic acid is unaffected by cross-sex hormone administration in transsexual subjects.

There is a close relationship between the brain and the endocrine system. The brain expresses receptors for sex steroids and is capable of metabolizing these hormones. We explored (1) sex differences in homovanillic acid (HVA), a metabolite of the neurotransmitter dopamine, and (2) the effects of cross-sex steroid administration in transsexual subjects. First, we compared plasma HVA levels between 38 male and 34 female healthy volunteers (not using hormone replacement therapy) of a mean age of 72 years (range 65-84 years). Secondly, we measured plasma HVA levels in 15 male-to-female transsexuals treated with 100 microg ethinyl estradiol/day and 100 mg cyproterone acetate/day for 4 months, and in 17 female-to-male transsexuals treated with testosterone esters (250 mg/2 weeks i.m. for 4 months). Plasma HVA levels were lower in elderly men than in elderly postmenopausal women (geometric mean 25.4 nmol/l (percentile (P)10 4.9; P90 69.8) vs 39.0 nmol/l (19.0; 76.1); P=0.027). In transsexuals before cross-sex hormone administration, genetic males also had lower plasma levels of HVA than genetic females (geometric mean 14.8 nmol/l (P10 7.0; P90 35.0) vs 34.3 nmol/l (21.8; 61.4); P<0.001). Cross-sex hormone administration did not affect plasma HVA in either group (P>0.5). The pretreatment sex difference in plasma HVA was unaffected after 4 months of cross-sex hormone administration (P=0.003). The sex difference in plasma HVA was not reversed by cross-sex hormone administration in transsexuals, and was also preserved in elderly subjects. This indicated that differences in dopamine gene expression were largely unaffected by exposure to sex hormone levels in adulthood, but must rather be explained by a sex difference in genetic factors or by the organizing effects of sex hormones during early development.

Aged, 80 and over↗

PubMed2004

Associations of sex-hormone-binding globulin (SHBG) with non-SHBG-bound levels of testosterone and estradiol in independently living men.

Results of in vitro experiments indicate that with increasing concentrations of SHBG, testosterone (T) is preferentially bound to SHBG in comparison with estradiol (E2). In these studies, the ratio of non-SHBG-bound E2 (non-SHBG-E2) to non-SHBG-T increased with increasing levels of SHBG. SHBG has consequently been regarded as an estrogen amplifier. In this cross-sectional study in 399 men aged between 40 and 80 yr we tested whether higher levels of SHBG are associated with a higher estrogen/androgen ratio in vivo. The mean T level of these men was in the eugonadal range [536 +/- 152 ng/dl (18.6 +/- 5.26 nmol/liter), mean +/- sd]. With increasing SHBG levels the non-SHBG-bound fraction of T decreased from 80 to 36% and that of E2 from 89 to 53%. Higher levels of SHBG were associated with higher levels of both total T [regression coefficient (beta) after adjustment for age and body mass index, 286 +/- 15.8; P < 0.001] and total E2 (beta = 4.47 +/- 0.90; P < 0.001). However, SHBG levels were negatively related with levels of non-SHBG-E2 (beta = -1.78 +/- 0.69; P < 0.001), whereas there was a positive association between levels of SHBG and non-SHBG-T (beta = 32.0 +/- 9.78; P = 0.001). Furthermore, we observed a negative relationship between SHBG levels and the E2/T ratio of either total (beta = -0.016 +/- 0.002; P < 0.001) or non-SHBG-bound (beta = -0.011 +/- 0.002; P < 0.001) hormone. Therefore, we conclude that in eugonadal men, higher SHBG levels are associated with lower levels of non-SHBG-E2 but slightly higher levels of non-SHBG-T. This means that SHBG cannot be regarded as an estrogen amplifier in eugonadal men.

Adult↗

PubMed2004

Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects.

BACKGROUND: During pregnancy there is a high demand for docosahexaenoic acid (DHA), which is needed for formation of the fetal brain. Women who do not consume marine foods must synthesize DHA from fatty acid precursors in vegetable foods. OBJECTIVE: We studied sex differences in DHA status and the role of sex hormones. DESIGN: First, DHA status was compared between 72 male and 103 female healthy volunteers who ate the same rigidly controlled diets. Second, the effects of sex hormones were studied in 56 male-to-female transsexual subjects, who were treated with cyproterone acetate alone or randomly assigned to receive oral ethinyl estradiol or transdermal 17beta-estradiol combined with cyproterone acetate, and in 61 female-to-male transsexual subjects, who were treated with testosterone esters or randomly assigned for treatment with the aromatase inhibitor anastrozole or placebo in addition to the testosterone regimen. RESULTS: The proportion of DHA was 15 +/- 4% (x +/- SEM; P < 0.0005) higher in the women than in the men. Among the women, those taking oral contraceptives had 10 +/- 4% (P = 0.08) higher DHA concentrations than did those not taking oral contraceptives. Administration of oral ethinyl estradiol, but not transdermal 17beta-estradiol, increased DHA by 42 +/- 8% (P < 0.0005), whereas the antiandrogen cyproterone acetate did not affect DHA. Parenteral testosterone decreased DHA by 22 +/- 4% (P < 0.0005) in female-to-male transsexual subjects. Anastrozole decreased estradiol concentrations significantly and DHA concentrations nonsignificantly (9 +/- 6%; P = 0.09). CONCLUSION: Estrogens cause higher DHA concentrations in women than in men, probably by upregulating synthesis of DHA from vegetable precursors.

Adult↗

PubMed2004

Transsexuals and competitive sports.

Men generally have an inherent performance advantage over women due to their average greater height and muscle mass and power, as the result of correspondingly different exposures to androgens. Therefore, it is considered fair that in sports men and women compete in separate categories. The question now emerging is whether reassigned transsexuals can compete in fairness with others of their new sex. The pertinent question is how far the previous effects of testosterone in male-to-female transsexuals (M-F) are reversible upon androgen deprivation so that M-F have no advantage over women, and, vice versa, what the effects are of androgen exposure in female-to-male transsexuals (F-M) on variables relevant to competition in sports. Before puberty, boys and girls do not differ in height, muscle and bone mass. Recent information shows convincingly that actual levels of circulating testosterone determine largely muscle mass and strength, though with considerable interindividual diversity. This study analyzed the effects of androgen deprivation in 19 M-F and of androgen administration to 17 F-M on muscle mass, hemoglobin (Hb) and insulin-like growth factor-1 (IGF-1). Before cross-sex hormone administration, there was a considerable overlap in muscle mass between M-F and F-M. In both M-F and F-M, height was a strong predictor of muscle mass. Androgen deprivation of M-F decreased muscle mass, increasing the overlap with untreated F-M, but mean muscle mass remained significantly higher in M-F than in F-M. Androgen administration to F-M increased muscle mass without inducing an advantage over nontreated M-F. The conclusion is that androgen deprivation in M-F increases the overlap in muscle mass with women but does not reverse it, statistically. The question of whether reassigned M-F can fairly compete with women depends on what degree of arbitrariness one wishes to accept, keeping in mind, for instance, that similar blood testosterone levels in men have profoundly different biologic effects on muscle properties, rendering competition in sports intrinsically a matter of how nature endows individuals for this competition.

Female↗

PubMed2004

Androgen replacement therapy: present and future.

The major goal of androgen substitution is to replace testosterone at levels as close to physiological levels as is possible. For some androgen-dependent functions testosterone is a pro-hormone, peripherally converted to 5alpha-dihydrotestosterone (DHT) and 17beta-estradiol (E2), of which the levels preferably should be within normal physiological ranges. Furthermore, androgens should have a good safety profile without adverse effects on the prostate, serum lipids, liver or respiratory function, and they must be convenient to use and patient-friendly, with a relative independence from medical services. Natural testosterone is viewed as the best androgen for substitution in hypogonadal men. The reason behind the selection is that testosterone can be converted to DHT and E2, thus developing the full spectrum of testosterone activities in long-term substitution. The mainstays of testosterone substitution are parenteral testosterone esters (testosterone enantate and testosterone cipionate) administered every 2-3 weeks. A major disadvantage is the strongly fluctuating levels of plasma testosterone, which are not in the physiological range at least 50% of the time. Also, the generated plasma E2 is usually supraphysiological. A major improvement is parenteral testosterone undecanoate producing normal plasma levels of testosterone for 12 weeks, with normal plasma levels of DHT and E2 also. Subcutaneous testosterone implants provide the patient, depending on the dose of implants, with normal plasma testosterone for 3-6 months. However, their use is not widespread. Oral testosterone undecanoate dissolved in castor oil bypasses the liver via its lymphatic absorption. At a dosage of 80 mg twice daily, plasma testosterone levels are largely in the normal range, but plasma DHT tends to be elevated. For two decades transdermal testosterone preparations have been available and have an attractive pharmacokinetic profile. Scrotal testosterone patches generate supraphysiological plasma DHT levels, which is not the case with the nonscrotal testosterone patches. Transdermal testosterone gel produces fewer skin irritations than the patches and offers greater flexibility in dosage. Oromucosal testosterone preparations have recently become available. Testosterone replacement is usually of long duration and so patient compliance is of utmost importance. Therefore, the patient must be involved in the selection of type of testosterone preparation. Administration of testosterone to young individuals has almost no adverse effects. With increasing age the risk of adverse effects on the prostate, the cardiovascular system and erythropoiesis increases. Consequently, short-acting testosterone preparations are better suited for aging androgen-deficient men.

Animals↗

PubMed2003

Transdermal testosterone delivery: testosterone patch and gel.

Testosterone replacement treatment is usually life-long. Fortunately, testosterone administration is relatively safe and until the age of 50 years few side effects are noted with normal doses of testosterone. After the age of 50 years when prostate disease becomes more prevalent, shorter-acting testosterone preparations, allowing a fast reduction of circulating testosterone levels, may be an advantage. Testosterone has an impact on sexual and non-sexual behaviour and short-acting testosterone preparations may be better suited for the initiation of long-term administration allowing the monitoring of behavioural effects. Testosterone can be delivered to the circulation through the intact skin, both genital and non-genital. Transdermal administration delivers testosterone at a controlled rate into the systemic circulation, avoiding hepatic first pass and reproducing the diurnal rhythm of testosterone secretion and without the peak and trough levels observed with the use of the traditional long-acting testosterone injections. In conclusion, both the testosterone patch and testosterone gel are valuable contributions to androgen replacement treatment meeting the requirements specified for testosterone replacement treatment.

Administration, Cutaneous↗

PubMed2003

Oral and transdermal estrogens both lower plasma total homocysteine in male-to-female transsexuals.

Plasma total homocysteine (tHcy) levels are on average lower in women versus men, indicating an estrogenic effect. Oral estrogens (absorbed via the liver) may be hypothesized to have stronger effects on hepatic homocysteine metabolism than transdermal estrogens. We randomly assigned 30 male-to-female transsexuals (20-44 years old) to 4 months' administration of oral ethinyl estradiol (n=15) or transdermal 17beta-estradiol (n=15), both with the antiandrogen cyproterone acetate (CA). Ten other male controls were treated with CA only. At baseline and after 2 and 4 months, plasma tHcy was analyzed in conjunction with plasma folate. Oral ethinyl estradiol and transdermal 17beta-estradiol similarly reduced plasma tHcy (geometric mean 10.6 micromol/l [95% CI 8.2-13.9] to 7.5 [6.5; 8.8], and 11.3 [8.1; 16.4] to 8.4 [6.5; 11.1]; P<0.001 for both), whereas CA had no effects. No effects were found on folate levels. Thus, oral and transdermal estrogens decrease plasma tHcy to a similar degree (by geometric mean -26%), which suggests that a hepatic mechanism is unlikely to play an important role in the decline of tHcy levels.

Administration, Cutaneous↗

PubMed2003

Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects.

OBJECTIVE: Sex differences are found in most components of the insulin resistance syndrome and the associated cardiovascular risk profile. These differences are attributed to sex-specific sex steroid profiles, but the effects of sex steroids on the individual components of the insulin resistance syndrome remain incompletely understood. DESIGN: Prospective, intervention study. SUBJECTS: In 37 young (age range 16-36 years), nonobese [body mass index (BMI) < 29], transsexual subjects, effects of ethinyl oestradiol (100 micro g/day) + cyproterone acetate (100 mg/day) administration were evaluated in 20 male-to-female transsexuals and of testosterone-ester administration [250 mg intramuscularly (i.m.)/2 weeks] in 17 female-to-male transsexuals. MEASUREMENTS: We studied lipid spectrum, postheparin hepatic lipase (HL) and lipoprotein lipase (LPL) activity, blood pressure, glucose utilization (by euglycaemic hyperinsulinaemic clamp), and fat areas (by magnetic resonance imaging) at baseline and during 1-year cross-sex hormone administration. RESULTS: Oestrogens + antiandrogens increased high-density lipoprotein (HDL)-cholesterol and decreased LDL-cholesterol, and HL activity, which are considered beneficial. But this combination also increased triglycerides, blood pressure, subcutaneous fat and visceral fat, and decreased the LDL-particle size, LPL activity and insulin sensitivity, which are all considered detrimental. Testosterone reduced HDL-cholesterol and the LDL-particle size, and increased triglycerides and HL activity. An android fat distribution was induced (i.e. decreased subcutaneous and increased visceral fat). Blood pressure, total and LDL-cholesterol, LPL activity and insulin sensitivity were mainly unaffected. CONCLUSIONS: The effects of cross-sex hormone treatment - in the dosages used in this study - in healthy, nonobese, young transsexual subjects do not show unequivocally that female sex steroids, given in large amounts to male subjects, have beneficial effects on cardiovascular profile and that high dose testosterone administration to female subjects is detrimental with respect to cardiovascular risk.

Adipose Tissue↗

PubMed2002

Androgens and male behavior.

Sexual differentiation into a male or a female includes sexual differentiation of the brain. The paradigm of mammalian sexual differentiation is that in the presence of androgens (normally produced by the fetal testis) a male brain differentiation occurs, while in the absence of androgens (normal in females) a female brain differentiation follows. In the human there is a sex-dimorphism in gender identity/role, sexual orientation, sexual functioning, and in non-sexual functions, such as spatial ability, and verbal fluency. Inasmuch these properties can be studied in other mammals the effects of androgens are solidly demonstrable. In the human the evidence for androgen effects is equally plausible, evident from observations in subjects with errors in the process of sexual differentiation and in morphological studies of brain structures presumably related to these properties. But clinical observations show compellingly that other, largely unidentified, factors may modulate, or even override the effects of androgens.

Affect↗

PubMed2002

The effect of beta-adrenergic blockade after encoding on memory of an emotional event.

RATIONALE: Animal and human studies lend support to the hypothesis that enhanced memory associated with emotional experiences involves activation of the beta-adrenergic system. Evidence for the role of noradrenaline in emotional memory in humans has been gathered from experimental studies where blockade of the beta-adrenergic system with a beta-blocker selectively impaired long-term memory for an emotionally arousing story (a slide show), when the beta-blocker was given before subjects were confronted with the emotional stimuli. OBJECTIVE: The purpose of this study was to test whether effective beta-adrenergic blockade occurring only after the stage of encoding has a similar impairing effect on memory. METHODS: In a double blind experimental design, 60 healthy adult subjects received randomly one tablet of either propranolol (Inderal, 40 mg) or placebo. Drugs were administered just before the slide show begun and (in view of its pharmacokinetics) propranolol reaches peak levels 1 h after drug intake. Physiological arousal was monitored by heart rate and blood pressure. Half of the beta-blocker and placebo groups watched either a neutral or an arousal version of an 11-slide presentation. Memory performance was tested with a surprise free recall and recognition test 1 week later. RESULTS: Memory performance, specifically for the second phase in which emotional elements were introduced, was better in subjects who viewed the arousal version than subjects who saw the neutral version of the slide show. However, no effect of the beta-blocker condition was found. CONCLUSION: This experiment does not support a role for noradrenaline in the post-encoding phase and on the later processes of consolidation and retrieval. Although it remains possible that with a different dosage or timing protocol a post-treatment effect of noradrenaline in humans can be found, this experiment could not find support for it.

Adrenergic beta-Antagonists↗