ResearchPad - sex-gender-and-hormones Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[OR27-05 Sexual Desire Changes in Transgender Individuals upon Initiation of Hormone Treatment; Results from the Longitudinal ENIGI Study]]> Introduction: Several steps in the transitioning process may affect sexual desire in transgender people. This is often underexposed by those providing gender affirming care. Testosterone therapy in transgender men (TM) generally leads to increasing frequency of desire, masturbation, sexual fantasies and arousal. Studies in transgender women (TW) are inconclusive: some report an increase in the prevalence of hypoactive sexual desire after initiation of hormone therapy, whereas others have shown a positive impact of hormonal therapy on sexual quality of life. The current study prospectively assesses sexual desire during the first three years of hormonal therapy (HT) in transgender people. Methods: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Sexual desire was prospectively assessed in 766 participants (401 TW, 364 TM) by Sexual Desire Inventory (SDI) during a three-year follow-up period, starting at the initiation of hormone treatment (HT). SDI scores were analyzed as total, dyadic and solitary SDI scores. At baseline, psychological questionnaires were administered. Sex steroids were measured at each follow-up visit. Data were analyzed cross-sectionally and prospectively. Results: In TW, total, dyadic and solitary SDI scores decreased during the first three months of HT. However, after 36 months, total and dyadic SDI scores were higher than baseline scores. Solitary scores after 36 months were comparable to baseline scores. In TM, total, dyadic and solitary SDI scores increased over the first three months, remaining stable thereafter. However, total and dyadic SDI scores after thirty-six months were comparable to baseline scores, whereas solitary scores remained higher than baseline. Factors associated with a prospective increase in SDI scores included having undergone gonadectomy, no longer experiencing vaginal bleedings (in TM) or higher gender dysphoria levels at baseline (in TM only). Factors associated with higher cross-sectional SDI scores included being in a relationship, undergoing gonadectomy, no longer experiencing vaginal bleedings (TM), lower gender dysphoria scores (TW only) and lower body dysphoria scores (TW only). Conclusion: Gender affirming hormonal therapy induces short-term changes in sexual desire in transgender people. Over a longer period of time, a net increase in dyadic sexual desire in TW receiving feminizing HT was observed. Sexual desire scores comparable to baseline in TM receiving virilizing HT were found. We observed no correlation between sexual desire and absolute serum testosterone levels. However, other factors, including undergoing gonadectomy, persistence of vaginal bleedings (in TM) and psychological factors may influence sexual desire in transgender people.

<![CDATA[OR27-04 Risk Factors For Low Baseline Bone Mineral Density In Gender Diverse Youth]]> Background

Sex steroids such as testosterone and estrogen are necessary for accumulation of bone mass. Transgender youth treated with gonadotropin releasing hormone analogues (GnRHa) to block natal puberty for gender-affirming care are at risk of low bone mineral density (BMD). Previous studies indicate that transfemale patients assigned male at birth (AMAB) have low BMD at baseline, during and after GnRHa treatment despite cross hormone treatment. Transmales assigned female at birth (AFAB), however, have normal BMD at baseline that decreases upon GnRHa treatment, with normalization upon cross hormone therapy. The reason(s) for the low baseline BMD in transfemales is unclear. We aimed to assess the baseline characteristics of transgender youth at a single multidisciplinary gender clinic prior to medical intervention and determine factors associated with BMD.


This is a retrospective chart review of patients <19 years old evaluated in the gender clinic. Dual-energy x-ray absorptiometry (DXA) scans were obtained prior to initiation of GnRHa or cross-hormone therapy per Endocrine Society guidelines for the treatment of gender dysphoria. We included patients with DXA scans completed prior to initiation of treatment with GnRHa or cross gender hormones and excluded those with concurrent medical diagnoses that may affect bone density. Data collected were bone mineral density (BMD) Z-scores, anthropometric data, vitamin D and calcium levels, and calcium intake. Multivariable linear regression models were used to assess the impact of vitamin D levels, height Z-score, weight Z-score, and BMI Z-score on subtotal body BMD Z-score, adjusted for sex assigned at birth and age.


Sixty-four patients were included in our analysis. Of these, 73% were AMAB and 27% AFAB. Gender identity was male in 14%, female in 44%, and non-binary in 42%. Average height Z-score was 0.12, weight Z-score 0.27, and BMI Z-score 0.22 (using sex assigned at birth). Subtotal body BMD Z-scores were greater than zero in 11%, between zero and greater than -2 in 59%, and less than or equal to -2 in 30% of tested patients. AMAB patients had lower BMD Z-scores compared to those AFAB (p<0.05 for all Z-scores). There was a positive association with BMI, height, and weight Z-scores and increasing BMD Z-scores after adjusting for sex assigned at birth and age (p<0.05 for all Z-scores). Patients who consumed <2 servings of calcium per day had lower BMD Z-scores (p<0.05 for all Z-scores). Average vitamin D level was 24 ng/ml (+/- 9.5 SD) with no significant association with BMD Z-scores (adjusted for sex assigned at birth).


Patients AMAB and patients with calcium intake of < 2 servings/day are associated with lower baseline BMD in a cohort of adolescents seen in a multidisciplinary gender clinic. Height, weight, and BMI are associated linearly with BMD Z-score, following patterns previously described in other populations.

<![CDATA[OR27-02 An Exploration of Novel Clinical Benchmarks for Assessing the Practice of Gonadectomy in Conditions Affecting Sex Development - on Behalf of the I-DSD Consortium]]> Introduction: Although the practice of gonadectomy in the field of differences/disorders of sex development (DSD) has undergone intense scrutiny, objective knowledge regarding current practice of gonadectomy is lacking in conditions affecting sex development. Methods: The International DSD Registry ( was examined for clinical information reported by the DSD specialist centre on age at presentation, year of birth, diagnosis, karyotype, sex of rearing and age at gonadectomy in all cases over the age of 16 years at the time of search and who had a disorder of androgen action or synthesis, gonadal dysgenesis or a non-specific DSD.Results: Of the 3,618 cases available in the registry, 757 (21%) met the inclusion criteria and data regarding gonadectomy status were available in 668 (88%) from 44 participating centres. Of these, 248 (37%) with a median age of 24 years (range 17, 75) were registered as male and 420 (63%) with a median age of 26 years (16, 86) were registered as female. Gonadectomy was reported from 36 centres in 351 of these 668 cases (53%) of whom 302 (86%) had a 46 XY karyotype. Females were more likely to undergo gonadectomy (n=311, p<0.0001) and the most common diagnoses were complete androgen insensitivity syndrome (n=161, 24%) and partial gonadal dysgenesis (n=94, 14%). Of the 351 cases, the primary indication for gonadectomy was reported in 268 (76%) cases and included mitigation of tumourigenesis risk in 172 (64%), conformity to sex assignment in 74 (28%) and another indication in 22 (8%). Gonadectomy was bilateral in 295 (84%), unilateral in 16 (5%) and unknown in 40 (11%). The median ratio for age at first presentation to age at gonadectomy in those who presented before the age of 5 years and those who presented after the age of 10 years was 0.1 (range) and 0.9 (range), respectively (p<0.0001). Of the 351 cases, 17 (5%) had undergone a gonadectomy before their first presentation to the specialist centre and these cases were distributed across 9 of the 36 centres. Conclusions: Not only does the rate of gonadectomy vary according to underlying diagnosis and sex of rearing, it also seems that there is a variable discrepancy between the age at presentation and age at gonadectomy. The use of this objective marker to identify trends in practice may improve our understanding of the causes of variation.

<![CDATA[OR27-07 11-oxygenated C19 Steroids in Normal Weight, Overweight, and Hyperandrogenic Girls]]> Hyperandrogenism (HA) often begins during puberty and may be a forerunner to polycystic ovary syndrome (PCOS). PCOS women have elevated 11-oxygenated androgens (O’Reilly MW et al, JCEM 2017), but the contribution of these androgens to HA in peri-pubertal girls is unknown. To address this uncertainty, we assessed classical and 11-oxygenated steroid levels at baseline and in response to both ACTH and recombinant human chorionic gonadotropin (r-hCG) administration in peri-pubertal girls. Girls (n=35) were studied in the mid-follicular phase (as relevant): age 13.1±3.1 (7.3-18.8) y (mean ± SD [range]); BMIz 1.1±1.1 (-1.08 to +2.65); Tanner breast 3.8±1.4 (1-5); bone age 14.1±3.1 (7.3-18) y. Of pre-menarcheal (PRE) girls, 4 were normal weight (NW, BMI% 5-84) and 7 overweight (OW, BMI% ≥ 85). Of post-menarcheal (POST) girls, 10 were NW, 6 OW, and 8 HA (3 NW, 5 OW). Blood was drawn at baseline (8 am, no meds); post-ACTH (60 m after 250 mcg IV, 10 h after dexamethasone [DEX, 1 mg PO]); and post-r-hCG (24 h after 50 mcg IV, 10 h after second dose DEX). Serum concentrations of classic (dehydroepiandrosterone [DHEA], androstenedione [A4], testosterone [T], dihydrotestosterone [DHT]) and 11-oxygenated androgens (11OHA4, 11KA4, 11OHT, and 11KT) were measured by liquid chromatography-tandem mass spectrometry. Wilcoxon Rank Sum and simple Spearman correlations were used for comparisons. Unless stated otherwise, p≤0.05 for all results reported below. At baseline, 11KT was 3-fold higher than T in PRE girls (1.2±0.6 vs. 0.4±0.2 nmol/L), while they did not differ in non-HA POST girls (1.4±0.6 vs. 1.1±0.5 nmol/L). The ratio of A4/T was 6.6±2.7 and 6.0±1.6 in PRE and non-HA POST girls, respectively, while 11KA4/11KT was 3.8±1.8 and 3.7±2.9, respectively; this suggests more efficient activation of 11-oxygenated androgens. Compared to NW POST girls, OW POST girls had higher T at baseline (1.9±0.9 vs. 1.2±0.8 nmol/L) and higher A4 post-ACTH (10.0±4.3 vs. 6.6±1.5 nmol/L). Compared to non-HA POST girls, HA girls had higher T at baseline (2.2±1.1 vs. 1.1±0.5 nmol/L) and higher DHEA, A4, and T post-r-hCG (DHEA: 8.8±2.7 vs. 5.6±2.2; A4: 11.3±4.1 vs. 7.3±2.8; T: 3.4±2.9 vs. 1.2±0.6 nmol/L). 11-oxygenated androgens were not elevated in OW or HA girls. In the entire cohort, HA status correlated with DHEA, A4, and T (r=0.40, 0.54, 0.63), while hirsutism correlated with A4 and T (r=0.47, 0.57). No androgen correlated with BMIz, but T correlated with fasting insulin and HOMA-IR (r=0.37, 0.38). The ratio of classic (DHEA, A4, T) to 11-oxygenated (11OHA4, 11KA4, 11OHT, 11KT) androgens trended higher in non-HA POST girls vs. PRE girls (58%:42% vs. 44%:56%, p=0.056). From early to late puberty, there appears to be a shift away from the 11-oxygenated pathway. Most androgens in HA girls derive from the classic androgen pathway. The mechanisms of the later switch to 11-oxygenated androgen pathway predominance in adult PCOS remain to be elucidated.

<![CDATA[OR27-03 Duration of Testosterone-Induced Acyclicity Influences Corpora Lutea Formation and Stromal Changes in a Transgender Mouse Model]]> The impact and reversibility of long-term gender-affirming testosterone (T) therapy on the reproductive axis of transgender men has not been well-established. Little is known about outcomes for transgender men interested in pausing T therapy to harvest oocytes or get pregnant. We previously established a translational mouse model to investigate T-induced acyclicity and ovarian perturbations. We hypothesized that the duration of T-induced acyclicity would impact the reversibility of cyclic and ovarian changes. To test this hypothesis, T-treated mice were assigned to two groups: (SHORT) 6 weeks of T therapy with immediate reversibility (1.5 mg T propionate pellet implant/removal, n = 5) and (LONG) 6 weeks of T therapy with a prolonged T washout phase (subcutaneous oil injections of T enanthate at 0.9 mg once weekly, n = 5). Control groups (placebo pellets n = 5, sesame oil vehicle injections n = 5) were run in parallel. Estrous cycles were monitored using daily vaginal cytology. Following cessation of T therapy, mice were sacrificed in diestrus after resumption of cyclicity for 4 cycles and ovarian histology examined. Data were analyzed in GraphPad Prism using Welch’s t-test or Mann-Whitney where appropriate. T therapy led to persistent diestrus within a week after T administration for all T-treated mice and none of the controls. The total duration of acyclicity was 6±1 weeks for the SHORT group, which was significantly shorter than the 11±2 weeks for the LONG group (mean ± s.d., p = 0.0079). With resumption of cyclicity, both the SHORT and LONG groups had a significantly lower percentage of days in estrus and higher percentage of days in metestrus as compared to their parallel age-matched controls. Ovarian histology for the SHORT group all showed regular corpora lutea and minimal stromal changes, however, 3/5 mice in the LONG group lacked corpora lutea and 4/5 revealed marked stromal cell hypertrophy. Similar stromal cell changes were not seen in control mice. In conclusion, the length of time of T-induced acyclicity appears to impact the development of stromal cell hypertrophy and formation of corpora lutea even after resumption of cyclicity with similar alterations to the estrous cycles. These findings may have clinical relevance for transgender men interested in fertility, based on duration of gender-affirming T therapy. Future work will aim to separate out the respective contributions of T exposure and acyclicity to the stromal phenotype.

<![CDATA[OR27-01 Combining Clinical and Genetic Approaches in Diagnosing a Large Brazilian Cohort of Patients with 46,XY Differences/Disorders of Sex Development (DSD)]]>


It is recommended a multidisciplinary approach consisted of clinical, hormonal and genetic workups for diagnosing 46,XY DSD. However, no previous study has quantified how useful is this combined approach.

To retrospectively review the clinical and genetic findings for diagnosing a large cohort of patients with 46,XY DSD from a single Brazilian center.

247 non-syndromic 46,XY DSD individuals (159 sporadic and 88 familial cases from 39 families) were studied. Clinical and hormonal data were collected from medical files. Testosterone (T), androstenedione (A) were measured by immunoradiometric or immunofluorimetric assays and dihydrotestosterone (DHT) by RIA after celite chromatography or by liquid chromatography tandem mass spectrometry; T/DHT and T/A ratios were calculated. Analysis of sensitivity (SE), specificity (SP) of T/DHT was performed, being the molecular diagnosis considered the gold standard for diagnosing SRD5A2 deficiency. A T/A>0.8 was considered indicative of 17ß-HSDB3 deficiency. The patients were clinically classified into four subgroups: 1) androgen insensitivity syndrome (AIS), 2) gonadal dysgenesis (GD); 3) defects in androgen synthesis (DAS) and 4) DSD of unknown etiology. Molecular studies were performed by Sanger sequencing and/ or massively parallel sequencing (MPS).

The median age at first visit was 14 years (range 0.1 to 59 years). The molecular diagnosis was established in 96.5% of the cases with AIS (n=28/29), in 96% of the subjects with DAS (n=46/48), in 36% of the patients with GD (n=21/57) and in 26.7% (n=15/56) with DSD of unknown etiology. The best cut-off for T/DHT in basal state and hCG stimulated was 12.5 (SE=100%; SP=78.57%) and 24 (SE=87.5%; SP=95.7%) respectively. A T/A<0.8 was observed in 13/16 (81%) of the patients with molecular diagnosis of 17ß-HSDB3 deficiency and also in 1/49 patients with other diagnose. Classification according to the phenotype matched with the genetic diagnosis in most cases. The molecular evaluation allowed that 16% (9/56) of the patients that were classified as DSD of unknow etiology had a definitive diagnosis, including six GD cases, two individuals with SRD5A2 deficiency and one with 17ß-HSDB3 deficiency. A clear AIS phenotype of five patients allowed us to consider and prove the pathogenicity of two synonymous and one promoter region variants as the cause of AIS. The combination of clinical and molecular diagnosis led to an increase in 8% the diagnosis in a total of 116 index-cases (58.5%) with a molecular diagnosis.

Considering the phenotype heterogeneity, pitfalls of the hormonal assessment and number of genes involved, it is reasonable to consider MPS as a first test for diagnosing patients with 46,XY DSD. However, the combination of clinical and molecular diagnosis is more accurate than either strategies alone in diagnosing 46,XY DSD.

<![CDATA[OR27-06 11-Oxygenated C19 Steroids Are Alternative Markers of Androgen Excess in Children with Premature Adrenarche and Premature Pubarche]]>