Longitudinal Case Study of Transgender Voice Changes Under Testosterone Hormone Therapy.
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ABSTRACT:
SUBMITTER: Cler GJ
PROVIDER: S-EPMC6790287 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe effect of gender affirming hormone therapy (GAHT) on clinical laboratory parameters, including levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), is an area of uncertainty in transgender health.AimWe sought to estimate the distribution parameters of liver enzyme levels among transmasculine (TM) and transfeminine (TF) persons receiving GAHT relative to the corresponding measures in cisgender reference groups, and to evaluate longitudinal changes in these laboratory measures following GAHT initiation.MethodsThe data for this longitudinal study included 624 TF and 438 transmasculine (TM) people as well as 4,090 cisgender males and 4,797 cisgender females enrolled in 3 integrated health systems. Time under observation was divided into 2 intervals: from the first blood test to the date of the first filled GAHT prescription and from GAHT initiation to the most recent ALT or AST measurement. Linear mixed models were used to compare changes in log-transformed ALT and AST values among transgender cohort members before and after GAHT initiation, and relative to the reference groups. The results were expressed as relative differences (in %) and the ratios of these differences (ratios-of-ratios) along with the 95% confidence intervals (CIs).OutcomesChanges in ALT and AST levels among transgender people over time and relative to the corresponding changes in cisgender referents.ResultsAmong TM study participants, the post GAHT ratios-of-ratios for AST were 1.61 (95% CI: 1.13, 2.31) and 1.57 (95% CI: 1.06, 2.31) relative to cisgender males and females respectively. For ALT, the corresponding comparisons yielded the ratios-of-ratios (95% CIs) of 2.06 (1.67, 2.54) and 1.90 (1.50, 2.40). No statistically significant changes were observed among TF participants. Other factors associated with higher liver enzyme levels included alcohol use/abuse and obesity.Clinical implicationsTM persons may experience modest increases in ALT and AST concentrations following testosterone initiation; however, clinical significance of the observed association remains unclear and requires further investigation. By contrast, feminizing GAHT is unlikely to induce appreciable changes in liver enzyme levels.Strength and limitationsThe strengths of this study are the longitudinal design and the ability to assemble an unselected cohort nested within large health systems. The main limitations include the lack of information on hormone levels and the inability to take into account GAHT doses and routes of administration.ConclusionThe influence of long-term GAHT on ALT and AST levels appears modest and not likely to reflect clinically meaningful changes in liver function. Hashemi L, Zhang Q, Getahun D, et al. Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy. J Sex Med 2021;18:1662-1675.
| S-EPMC8444147 | biostudies-literature
Project description:ObjectivesThis prospective study was designed to investigate the effect of testosterone, delivered by subcutaneous implants, on the female voice.MethodsTen women who had opted for testosterone therapy were recruited for voice analysis. Voices were recorded prior to treatment and at 3 months, 6 months, and 12 months while on testosterone therapy. Acoustic samples were collected with subjects reading a sentence, reading a paragraph, and participating in a conversation. Significant changes in the voice over time were investigated using a repeated-measures analysis of variance with the fundamental frequency (F0) as a response variable. Demographic variables associated with characteristics of the voice were assessed.ResultsThere were no significant differences in average F0 related to smoking history, menopausal status, weight, or body mass index. There was no difference in average fundamental speaking frequency (sentence, paragraph, conversation) between the pre-treatment group and any post-treatment group at 3 and 12 months. There was an increase in sentence speech F0 at 6 months. Two of three patients with lower than expected F0 at baseline improved on testosterone therapy.ConclusionTherapeutic levels of testosterone, delivered by subcutaneous implant, had no adverse affect on the female voice including lowering or deepening of the voice.
| S-EPMC4819813 | biostudies-literature
Project description:Testosterone therapy (TT) is administered to enhance masculinization in transgender individuals. The long-term effect of exogenous testosterone on breast tissues remains unclear. Our study evaluated the modulation of breast morphology by TT in transgender individuals with special attention to duration of TT. We reviewed 447 breast surgical specimens from gender affirming chest-contouring surgery, and compared histopathological findings including degree of lobular atrophy, and atypical and non-atypical proliferations between subjects who did (n = 367) and did not (n = 79) receive TT. TT for one patient was unknown. TT for >12 months was associated with seven histopathological features. Longer duration of TT was significantly associated with higher degrees of lobular atrophy (p < 0.001). This relationship remained significant after accounting for age at surgery, ethnicity, body mass index, and presurgical oophorectomy (adjusted p < 0.001). Four types of lesions were more likely to be absent in breast tissues exposed to longer durations of TT: cysts (median = 16.2 months; p < 0.01; adjusted p = 0.01), fibroadenoma (median = 14.8 months; p = 0.02; adjusted p = 0.07), pseudoangiomatous stromal hyperplasia (median = 17.0 months; p < 0.001; adjusted p < 0.001), and papillomas (median = 14.7 months; p = 0.04; adjusted p = 0.20). Columnar cell change and mild inflammation were also less likely to occur in subjects receiving TT (p < 0.05), but were not linked to the duration of TT. Atypia and ductal carcinoma in situ were detected in 11 subjects (2.5%) all of whom received TT ranging from 10.1 to 64.1 months. The incidental findings of high-risk lesions and carcinoma as well as the risk of cancer in residual breast tissue after chest-contouring surgery warrant the consideration of culturally sensitive routine breast cancer screening protocols for transgender men and masculine-centered gender nonconforming individuals. Long-term follow-up studies and molecular investigations are needed to understand the breast cancer risk of transgender individuals who receive TT.
| S-EPMC7854981 | biostudies-literature
Project description:Some transmasculine individuals may be interested in pausing gender-affirming testosterone (T) therapy and carrying a pregnancy. The ovarian impact of taking and pausing T is not completely understood. The objective of this study was to utilize a mouse model mimicking transmasculine T therapy to characterize the ovarian dynamics following T cessation. We injected postpubertal 9–10-week-old female C57BL/6N mice once weekly with 0.9 mg of T enanthate or a vehicle control for six weeks. All T-treated mice stopped cycling and demonstrated persistent diestrus within one week of starting T therapy, while control mice cycled regularly. After 6 weeks of T therapy, one group of T-treated mice and age-matched vehicle-treated diestrus controls were sacrificed. Another group of T-treated mice were maintained after stopping T therapy and sacrificed in diestrus four cycles after the resumption of cyclicity along with age-matched vehicle-treated controls. Ovarian histological analysis revealed stromal changes with clusters of large round cells in the post T group as compared to both age-matched controls and mice at six weeks on T. These clusters exhibited periodic acid-Schiff staining, which has been previously reported in multinucleated macrophages in aging mouse ovaries. Notably, many of these cells also demonstrated positive staining for macrophage markers CD68 and CD11b. Ovarian RNA sequencing found upregulation of immune pathways post T as compared to age-matched controls and ovaries at six weeks on T. Although functional significance remains unknown, further attention to the ovarian stroma may be relevant for transmasculine people interested in pausing T to carry a pregnancy.
2023-02-21 | GSE200502 | GEO
Project description:To determine dose-dependent effects of T administration on voice changes in women with low T levels.Seventy-one women who have undergone a hysterectomy with or without oophorectomy with total T < 31 ng/dL and/or free T < 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly im injections of placebo or 3, 6.25, 12.5, or 25 mg T enanthate for 24 weeks. Total and free T levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. Voice handicap was measured by self-report using a validated voice handicap index questionnaire at baseline and 24 weeks after intervention. Functional voice testing was performed using the Kay Elemetrics-Computer Speech Lab to determine voice frequency, volume, and harmonics.Forty-six women with evaluable voice data at baseline and after intervention were included in the analysis. The five groups were similar at baseline. Mean on-treatment nadir total T concentrations were 13, 83, 106, 122, and 250 ng/dL in the placebo, 3-, 6.25-, 12.5-, and 25-mg groups, respectively. Analyses of acoustic voice parameters revealed significant lowering of average pitch in the 12.5- and 25-mg dose groups compared to placebo (P < .05); these changes in pitch were significantly related to increases in T concentrations. No significant dose- or concentration-dependent changes in self-reported voice handicap index scores were observed.Testosterone administration in women with low T levels over 24 weeks was associated with dose- and concentration-dependent decreases in average pitch in the higher dose groups. These changes were seen despite the lack of self-reported changes in voice.
| S-EPMC4454796 | biostudies-literature
Project description:BackgroundObesity is associated with low testosterone levels that could be caused by many mechanisms. Adropin, a peptide hormone, its levels are decreased in obesity and its receptors are expressed in the hypothalamus, the pituitary gland, and the testis. Adropin association to total testosterone in obese men is not detected yet. This study tries to find out possible associations between serum levels of adropin, adiponectin, total testosterone, and lipid profile in obese men.MethodsSerum levels of adropin, adiponectin, total testosterone, and lipid profile parameters were measured in 43 obese men and 40 age-matched normal-weight men.ResultsAdropin, adiponectin, and testosterone levels were significantly lower in obese men versus normal-weight men. In all participants, positive correlations between adropin, adiponectin, and total testosterone were detected. Adropin is considered a predictor risk factor for testosterone.ConclusionsThis study suggests a possible causal relationship between adropin and total testosterone which needs further investigation.Trial registrationClincialtrials.gov NCT03724825 , registered October 30th, 2018.
| S-EPMC9327160 | biostudies-literature
Project description: Not available
| S-EPMC10424140 | biostudies-literature
Project description:OBJECTIVES:There is a dearth of information on transgender individuals in Nepal, particularly studies exploring their use of hormone therapies. The objectives of this study therefore were to explore (1) how hormones are used, (2) types of hormones used and (3) side effects experienced by transgender women after hormone use. This is the first study of its kind in Nepal addressing this important public health issue. SETTING:The study was conducted in four districts of Nepal: Kathmandu, Sunsai, Banke and Kaski. DESIGN AND PARTICIPANTS:This qualitative study comprises eight focus group discussions (FGDs) and nine interviews. FGDs and three face-to-face interviews were held with transgender women aged 18 years and older and six interviews with stakeholders working with and advocating on behalf of this population. The study was conducted between September 2016 and March 2017. RESULTS:Our participants were young. The majority of FGD participants had completed school-level education and 40% had been using hormones for 1 to 3 years. Five overlapping themes were identified: (1) reasons and motivations for hormone use; (2) accessibility and use of hormones; (3) side effects; (4) utilisation of healthcare services and (5) discontinuation of hormone use. CONCLUSION:Hormone use was common in our sample. Most received information on hormone therapy online and through their peer networks. A few study participants sought doctors' prescriptions for hormone therapy, but hormones were more likely to be bought from local private pharmacies or abroad through friends. This kind of self-medication is associated with a range of risks to the physical and mental health of transgender individuals. Incorporating information, education and communication about hormone therapy into existing health promotion interventions targeted to this population may help transgender people to make better informed choices.
| S-EPMC6830677 | biostudies-literature
Project description:A comparison of rectal mucosal RNA transcriptome findings between transgender women using feminizing hormone therapy, men who have sex with men engaging in receptive anal intercourse, and males who had never engaged in anal intercourse demonstrates differential gene expression involving pathways critical for mucosal inflammation, suggesting the urgent need for further exploration into the immunologic effects of cross-sex hormone therapy in the rectal mucosa and the potential impact on HIV transmission risk at this site.
2023-03-21 | GSE141785 | GEO
Project description:INTRODUCTION:Concerns over potential drug-drug interactions (DDI) between feminizing hormone therapy (FHT) and pre-exposure prophylaxis (PrEP) have hampered uptake and adherence of PrEP among transgender women (TGW). To determine DDI between FHT and PrEP, we measured the pharmacokinetic (PK) parameters of blood plasma estradiol (E2) and tenofovir (TFV) in Thai TGW. METHODS:Twenty TGW who never underwent orchiectomy and had not received injectable FHT within six months were enrolled between January and March 2018. FHT (E2 valerate and cyproterone acetate) were prescribed to participants at baseline until week 5, and then from week 8 until the end of study. Daily PrEP (tenofovir disoproxil fumarate/emtricitabine) was initiated at week 3 and continued without interruption. Intensive E2 PK parameters and testosterone concentration at 24 hours (C24 ) were measured at weeks 3 (without PrEP) and 5 (with PrEP), and intensive TFV PK parameters were measured at weeks 5 (with FHT) and 8 (without FHT). RESULTS:Median (interquartile range) age, body mass index, and creatinine clearance were 21.5 (21-26) years, 20.6 (19.0-22.4) kg/m2 , and 116 (101-126.5) mL/min, respectively. The geometric mean (%CV) of area under curve from time zero to 24 hours (AUC0-24 ), maximum concentration (Cmax ), and C24 of E2 at weeks 3 and 5 were 775.13 (26.2) pg h/mL, 51.47 (26.9) pg/mL, and 15.15 (42.0) pg/mL; and 782.84 (39.6), 55.76 (32.9), and 14.32 (67.4), respectively. The geometric mean (%CV) of TFV AUC0-24 , Cmax , and C24 at weeks 5 and 8 were 2242.1 (26.5) ng h/mL, 353.9 (34.0) ng/mL, and 40.9 (31.4) ng/mL; and 2530.2 (31.3), 311.4 (30.0), and 49.8 (29.6), respectively. The geometric mean of TFV AUC0-24 and C24 at week 5 were significantly less than that at week 8 by 12% (p = 0.03) and 18% (p < 0.001), respectively. There were no significant changes in E2 PK parameters and median C24 of bioavailable testosterone between week 3 and week 5. CONCLUSIONS:Our study demonstrated lower blood plasma TFV exposure in the presence of FHT, suggesting that FHT may potentially affect PrEP efficacy among TGW; but E2 exposure was not affected by PrEP. Further studies are warranted to determine whether these reductions in TFV are clinically significant. Clinical Trial Number: NCT03620734.
| S-EPMC6625338 | biostudies-literature