Effects of intramuscular testosterone undecanoate on body composition and bone mineral density in female-to-male transsexuals.

INTRODUCTION: The most common treatment regimen in female-to-male transsexuals is administration of short-acting testosterone esters intramuscularly every 2 weeks. AIM: The aim of this study was to evaluate the effect of long-acting intramuscular testosterone undecanoate on body composition and bone mineral density during cross-sex hormone therapy in female-to-male transsexuals. METHODS: Forty-five female-to-male transsexuals (FtMs) were treated with injections of testosterone undecanoate 1,000 mg intramuscularly every 12 weeks over 24 months. MAIN OUTCOME MEASURES: Body composition, bone mineral density, hormone parameters, and lipids were compared after 12 months and after 24 months with baseline values. Sonographic findings in the ovaries and endometrium, clinical and adverse effects during the study period were recorded. RESULTS: There was a significant increase in lean mass in the FtMs during the study period in comparison with baseline values, whereas no change in BMI, fat mass, and bone mineral density was observed. There was a significant decline in gonadotropins, estradiol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, and high-density lipoprotein, while testosterone and triglyceride levels increased significantly after 12 and 24 months. Ovaries remained unchanged and no noticeable endometrial pathology was observed. No mortality or morbidity was observed during the study period. We observed a cessation of menstrual bleeding, an increase in clitoral growth, libido, body and beard hair growth, deepened voices and decline in breast size. There was a significant increase in hemoglobin, hematocrit, glutamic-pyruvic transaminase, gamma-glutamyl transferase, and an increase in systolic blood pressure during the study period. CONCLUSIONS: There was an increase in lean mass during the study period in FtMs treated with testosterone undecanoate. Transsexual patients should be monitored for adverse effects on lipid profiles, blood pressure, and erythrocytosis during intramuscular testosterone undecanoate therapy.

The impact of testosterone administration to female-to-male transsexuals on insulin resistance and lipid parameters compared with women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the impact of testosterone (T) administration to female-to-male transsexuals (FtMs) on insulin resistance and lipid parameters and to compare the effects with women with polycystic ovary syndrome (PCOS). DESIGN: Cohort analysis. SETTING: University hospital. PATIENT(S): Twenty-nine FtMs and 240 women with PCOS. INTERVENTION(S): Screening panel, ultrasound of the ovaries, hormone, lipid, and glucose and insulin measurements. MAIN OUTCOME MEASURE(S): Endocrine, metabolic parameters, and insulin resistance. RESULT(S): The PCOS women had significantly higher fasting, 1-h, and 2-h insulin levels and a significantly lower insulin sensitivity index compared with FtMs before and after their T treatment. There were higher triglyceride levels and lower high-density lipoprotein cholesterol levels upon T treatment in FtMs compared with the PCOS women. Women with PCOS had higher body mass index (BMI) values. Positive correlations between insulin resistance indices and BMI were found only in women with PCOS. CONCLUSION(S): Testosterone administration by itself showed little detrimental influence on insulin resistance indices, but it had significant effects on lipid profiles. Compared with T, BMI had a greater impact on insulin resistance in women with PCOS.

Smoking is associated with increased free testosterone and fasting insulin levels in women with polycystic ovary syndrome, resulting in aggravated insulin resistance.

OBJECTIVE: To evaluate the impact of smoking on endocrine, metabolic, and clinical parameters in women with polycystic ovary syndrome (PCOS). DESIGN: Cohort analysis. SETTING: University hospital. PATIENT(S): 346 women with PCOS, including 98 smokers and 248 nonsmokers. INTERVENTION(S): Screening panel, including physical examination, weight and height measurement, and ultrasound examination of the ovaries, and hormone and insulin measurements. MAIN OUTCOME MEASURE(S): Clinical, metabolic, and endocrine parameters, oral glucose tolerance test, calculation of insulin resistance indexes. RESULT(S): In women with PCOS, smoking was associated with statistically significantly increased levels of fasting insulin and calculated free testosterone (cFT) and with a raised free androgen index (FAI) score, which resulted in aggravated scores on the homeostatic model for assessment of insulin resistance (HOMA-IR). However, no differences were observed between the smoking and nonsmoking groups with regard to the clinical parameters for hirsutism, acne, ovulatory function (classified as eumenorrhea, oligomenorrhea, and amenorrhea), or polycystic ovaries using the ultrasound criteria recommended according to the Rotterdam definition. CONCLUSION(S): In women with PCOS, smoking is associated with increased free testosterone and fasting insulin levels, resulting in aggravated insulin resistance. However, there were no differences between smokers and nonsmokers when clinical parameters were compared.

Effects of transdermal testosterone or oral dydrogesterone on hypoactive sexual desire disorder in transsexual women: results of a pilot study.

OBJECTIVE: It has been reported that hypoactive sexual desire disorder (HSDD) affects one-third of transsexual women (defined as postoperative male-to-female transsexuals) receiving estrogen replacement whose bioavailable androgen levels are lower than in ovulating women and comparable with those in surgically postmenopausal women. The aim of this study was to evaluate the efficacy of transdermal testosterone treatment and of oral dydrogesterone in transsexual women with HSDD receiving estrogens. METHODS: Seven transsexual women with HSDD were treated with a testosterone patch and nine transsexual women with HSDD were treated with oral dydrogesterone over 24 weeks. The primary end point was the change in the brief profile of female sexual function (B-PFSF) score. Secondary end points were changes in hormonal parameters and side effect assessments. RESULTS: A significant increase in total testosterone and free testosterone levels was observed in the group receiving transdermal testosterone. At 24 weeks, there was a significant improvement in the B-PFSF score showing an improvement in sexual desire among transsexual women treated with the testosterone patch, whereas no change in the B-PFSF score was observed in transsexual women treated with oral dydrogesterone. No side effects were reported. CONCLUSIONS: In this pilot study, sexual desire in transsexual women improved significantly after treatment with the testosterone patch, without noticeable side effects.

mRNA-mediated gene delivery into human progenitor cells promotes highly efficient protein expression.

Gene transfer into human CD34+ haematopoietic progenitor cells (HPC) and multi-potent mesenchymal stromal cells (MSC) is an essential tool for numerous in vitro and in vivo applications including therapeutic strategies, such as tissue engineering and gene therapy. Virus based methods may be efficient, but bear risks like tumorigenesis and activation of immune responses. A safer alternative is non-viral gene transfer, which is considered to be less efficient and accomplished with high cell toxicity. The truncated low affinity nerve growth factor receptor (ALNGFR) is a marker gene approved for human in vivo application. Human CD34+ HPC and human MSC were transfected with in vitro-transcribed mRNA for DeltaLNGFR using the method of nucleofection. Transfection efficiency and cell viability were compared to plasmid-based nucleofection. Protein expression was assessed using flow cytometry over a time period of 10 days. Nucleofection of CD34+ HPC and MSC with mRNA resulted in significantly higher transfection efficiencies compared to plasmid transfection. Cell differentiation assays were performed after selecting DeltaLNGFR positive cells using a fluorescent activating cell sorter. Neither cell differentiation of MSC into chondrocytes, adipocytes and osteoblasts, nor differentiation of HPC into burst forming unit erythroid (BFU-E) colony forming unit-granulocyte, erythrocyte, macrophage and megakaryocyte (CFU-GEMM), and CFU-granulocyte-macrophage (GM) was reduced. mRNA based nucleofection is a powerful, highly efficient and non-toxic approach for transient labelling of human progenitor cells or, via transfection of selective proteins, for transient manipulation of stem cell function. It may be useful to transiently manipulate stem cell characteristics and thus combine principles of gene therapy and tissue engineering.