Effects of testosterone treatment on clitoral haemodynamics in women with sexual dysfunction.

PURPOSE: To explore the effects of 6-month systemic testosterone (T) administration on clitoral color Doppler ultrasound (CDU) parameters in women with female sexual dysfunction (FSD). METHODS: 81 women with FSD were retrospectively recruited. Data on CDU parameters at baseline and after 6 months with four different treatments were available and thus further longitudinally analyzed: local non-hormonal moisturizers (NH group), n = 37; transdermal 2% T gel 300 mcg/day (T group), n = 23; local estrogens (E group), n = 12; combined therapy (T + E group), n = 9. Patients underwent physical, laboratory, and genital CDU examinations at both visits and completed different validated questionnaires, including the Female Sexual Function Index (FSFI). RESULTS: At 6-month visit, T therapy significantly increased clitoral artery peak systolic velocity (PSV) when compared to both NH (p < 0.0001) and E (p < 0.0001) groups. A similar increase was found in the T + E group (p = 0.039 vs. E). In addition, T treatment was associated with significantly higher FSFI desire, pain, arousal, lubrication, orgasm, and total scores at 6-month visit vs. baseline. Similar findings were observed in the T + E group. No significant differences in the variations of total and high-density lipoprotein-cholesterol, triglycerides, fasting glycemia, insulin and glycated hemoglobin levels were found among the four groups. No adverse events were observed. CONCLUSION: In women complaining for FSD, systemic T administration, either alone or combined with local estrogens, was associated with a positive effect on clitoral blood flow and a clinical improvement in sexual function, showing a good safety profile. TRIAL REGISTRATION NUMBER: NCT04336891; date of registration: April 7, 2020.

Testosterone and Exercise in Middle-to-Older Aged Men: Combined and Independent Effects on Vascular Function.

[Figure: see text].

Beyond Gender Identity Disorder Diagnoses Codes: An Examination of Additional Methods to Identify Transgender Individuals in Administrative Databases.

BACKGROUND: Large administrative databases often do not capture gender identity data, limiting researchers' ability to identify transgender people and complicating the study of this population. OBJECTIVE: The objective of this study was to develop methods for identifying transgender people in a large, national dataset for insured adults. RESEARCH DESIGN: This was a retrospective analysis of administrative claims data. After using gender identity disorder (GID) diagnoses codes, the current method for identifying transgender people in administrative data, we used the following 2 strategies to improve the accuracy of identifying transgender people that involved: (1) Endocrine Disorder Not Otherwise Specified (Endo NOS) codes and a transgender-related procedure code; or (2) Receipt of sex hormones not associated with the sex recorded in the patient's chart (sex-discordant hormone therapy) and an Endo NOS code or transgender-related procedure code. SUBJECTS: Seventy-four million adults 18 years and above enrolled at some point in commercial or Medicare Advantage plans from 2006 through 2017. RESULTS: We identified 27,227 unique transgender people overall; 18,785 (69%) were identified using GID codes alone. Using Endo NOS with a transgender-related procedure code, and sex-discordant hormone therapy with either Endo NOS or transgender-related procedure code, we added 4391 (16%) and 4051 (15%) transgender people, respectively. Of the 27,227 transgender people in our cohort, 8694 (32%) were transmasculine, 3959 (15%) were transfeminine, and 14,574 (54%) could not be classified. CONCLUSION: In the absence of gender identity data, additional data elements beyond GID codes improves the identification of transgender people in large, administrative claims databases.

"I Couldn't See a Downside": Decision-Making About Gender-Affirming Hormone Therapy.

PURPOSE: The aim of the article was to understand adolescents' and parents' decision-making process related to gender-affirming hormone therapy (GAHT). METHODS: We conducted qualitative semistructured interviews with transgender adolescents who began testosterone for GAHT in the prior year and the parents of such adolescents. Questions focused on decision-making roles, steps in the decision process, and factors considered in the decision. Participants used pie charts to describe the division of responsibility for the decision. All interviews were coded by at least two members of the research team with disagreements resolved through discussion. Thematic analysis was used to analyze the data. RESULTS: Seventeen adolescents and 13 parents were interviewed (12 dyads). The process of deciding about GAHT involves a series of small conversations, typically with the adolescent advocating to start treatment and the parent feeling hesitant. In most cases, after seeking information from the Internet, healthcare providers and personal contacts move toward acceptance and agree to start treatment. Although adolescents have some short-term concerns, such as about needles, parents' concerns relate more to long-term risks. Ultimately, for both parents and adolescents, the benefits of treatment outweigh any concerns, and they are in agreement about the goals of personal confidence, comfort in one's body and happiness. CONCLUSIONS: To the extent that the decision about GAHT is a medical decision, the decision process is similar to others. However, decisions about GAHT are much more about gender identity than medical risks, suggesting that interventions based in a medical framework may not aid in supporting decision-making.

Cross-sex hormonal treatment and body uneasiness in individuals with gender dysphoria.

INTRODUCTION: Cross-sex hormonal treatment (CHT) used for gender dysphoria (GD) could by itself affect well-being without the use of genital surgery; however, to date, there is a paucity of studies investigating the effects of CHT alone. AIMS: This study aimed to assess differences in body uneasiness and psychiatric symptoms between GD clients taking CHT and those not taking hormones (no CHT). A second aim was to assess whether length of CHT treatment and daily dose provided an explanation for levels of body uneasiness and psychiatric symptoms. METHODS: A consecutive series of 125 subjects meeting the criteria for GD who not had genital reassignment surgery were considered. MAIN OUTCOME MEASURES: Subjects were asked to complete the Body Uneasiness Test (BUT) to explore different areas of body-related psychopathology and the Symptom Checklist-90 Revised (SCL-90-R) to measure psychological state. In addition, data on daily hormone dose and length of hormonal treatment (androgens, estrogens, and/or antiandrogens) were collected through an analysis of medical records. RESULTS: Among the male-to-female (MtF) individuals, those using CHT reported less body uneasiness compared with individuals in the no-CHT group. No significant differences were observed between CHT and no-CHT groups in the female-to-male (FtM) sample. Also, no significant differences in SCL score were observed with regard to gender (MtF vs. FtM), hormone treatment (CHT vs. no-CHT), or the interaction of these two variables. Moreover, a two-step hierarchical regression showed that cumulative dose of estradiol (daily dose of estradiol times days of treatment) and cumulative dose of androgen blockers (daily dose of androgen blockers times days of treatment) predicted BUT score even after controlling for age, gender role, cosmetic surgery, and BMI. CONCLUSIONS: The differences observed between MtF and FtM individuals suggest that body-related uneasiness associated with GD may be effectively diminished with the administration of CHT even without the use of genital surgery for MtF clients. A discussion is provided on the importance of controlling both length and daily dose of treatment for the most effective impact on body uneasiness.

Stimulatory effect of gonadal hormones on fetal rat hippocampal neural proliferation requires neurotrophin receptor activation in vitro.

To determine the effects of gonadal hormones on proliferation of the hippocampal neural cells, which are of importance in learning and memory function. 17ß-Estradiol or testosterone was added to the culture at various concentrations. Their proliferation and protective effects on the neural cell were determined with BrdU, flow cytometry and MTT assay. Effects of the gonadal hormones on brain-derived neurotrophic factor (BDNF) expression were determined using ELISA and RT-PCR respectively. 17ß-Estradiol and testosterone at 20nM or higher concentrations significantly increased the neural cell proliferation and viability, and induced increasing in the S phase arrest which is essential for cell proliferation. Both estradiol and testosterone significantly increased the neural cell expression of cellular mature BDNF and BDNF mRNA. Effect of testosterone on hippocampal neural proliferation was blocked by Trk neurotrophin receptor inhibitor. 17ß-Estradiol and testosterone promoted hippocampal neural proliferation and improved cell viability in vitro. The effect of testosterone on hippocampal neural cell proliferation required neurotrophin receptor activation.

Influence of gender and estrous cycle on plasma and renal catecholamine levels in rats.

Several studies have demonstrated that gonadal hormones show significant effects on the brain and signaling pathways of effector organs/cells that respond to neurotransmitters. Since little information is available concerning the impact of male and female gonadal hormones on the renal and peripheral sympathetic system, the objective of this study was to further assess whether and how the renal content and plasma concentration of catecholamines are influenced by gender and the estrous cycle in rats. To achieve this, males Wistar rats were divided into 4 groups: (i) sham (i.e., control), (ii) gonadectomized, (iii) gonadectomized and nandrolone decanoate replacement at physiological levels or (iv) gonadectomized and nandrolone decanoate replacement at high levels. Female Wistar rats were divided into 6 groups: (i) ovariectomized (OVX), (ii) estrogen replacement at physiological levels and (iii) estrogen replacement at at high levels, (iv) progesterone replacement at physiological levels and (v) progesterone replacement at at high levels, and (vi) sham. The sham group was subdivided into four subgroups: (i) proestrus, (ii) estrus, (iii) metaestrus, and (iv) diestrus. Ten days after surgery, the animals were sacrificed and their plasma and renal catecholamine levels measured for intergroup comparisons. Gonadectomy led to an increase in the plasma catecholamine concentration in females, as well as in the renal catecholamine content of both male and female rats. Gonadectomized males also showed a lower level of plasma catecholamine than the controls. The urinary flow, and the fractional excretion of sodium and chloride were significantly increased in gonadectomized males and in the OVX group when compared with their respective sham groups.

Sex differences and influence of gonadal hormones on MK801-induced neuronal degeneration in the granular retrosplenial cortex of the rat.

MK801, PCP, and ketamine are non-competitive NMDA receptor-antagonists drugs that in humans produce psychomimetic effects and neurocognitive disturbances reminiscent to those of schizophrenia. The administration of these drugs in animals has been used as a pharmacological model to study the NMDA receptor hypofunction-hypothesis of schizophrenia. In animals, the biological effect of MK801 is dose-dependent. Low doses induce behavioral disturbances and higher doses, in addition, promote neurotoxicity in many brain regions, particularly the granular retrosplenial cortex (RSG). The neurotoxic effect of MK801 is sexually dimorphic, being females markedly more sensitive than males; however, the involvement of gonadal hormones is elusive. Here we show that a single intraperitoneal injection of 5 mg/kg of MK801 induced overt neurodegeneration in RSG of female rats, including abundant somatic degeneration in layer 4, and somatodendritic and terminal degeneration in layers 1, 4, and 5. MK801-degeneration in males was scarce and mainly evidenced by the presence of few argirophilic somas in layer 4. Ovariectomized rats were not significantly different than intact females, while orchiectomized rats showed robust MK801-toxicity. Testosterone and dihydrotestosterone (DHT) inhibit MK801-toxicity in orchiectomized rats. In ovariectomized rats only DHT, but not testosterone, prevented MK801-induced degeneration, while in intact females, DHT was only partially protective. Treatment of intact males with estradiol benzoate significantly enhanced MK801-toxicity. Altogether, our experiments indicate that non-aromatizable androgens protect RSG from MK801-toxicity, while estrogens counteract this protection. Thus, the balance of androgens and estrogens delineate the sexual dimorphism of the RSG to the toxic effect of MK801.

Influence of progesterone, pregnenolone and 17beta-hydroxyprogesterone on the function of bovine luteal cells treated with luteinizing hormone, noradrenaline and prostaglandin E2.

The aim of the present study was to investigate the influence of progesterone (P4), its precursor (pregnenolone; P5) and metabolite (17beta-hydroksyprogesterone; 17betaOHP4) on secretory function of bovine luteal cells on days 6-10 of the estrous cycle and on intracellular Ca2+ mobilization. The luteal cells were pre-incubated for 24 h and after change of medium they were incubated for 30 min with P5 and 17betaOHP4 (10(-5) each). Next, the medium was supplemented with LH (100 ng/ml), noradrenaline (NA; 10(-5) M) and prostaglandin (PG)E2 (10(-6) M), the cells were incubated for further 4 h and the medium was collected for P4 determination. Another set of luteal cells (5x10(4)/well) was incubated with P4, P5 and 17betaOHP4 at the dose of 10(-5) M each for 30 min and intracellular Ca2+ mobilization was measured every 5 s three times before and for 60 s after cells stimulation with LH, NA and PGE2. Metabolite of P4 did not affect the stimulatory effect of LH, PGE2 and NA on P4 secretion to the medium. Whereas all used steroids reduced calcium release from small but not from large luteal cells. It is suggested that steroids could temporary impair effect of luteotropins on the luteal cells via non-genomic way.

The current status of therapy for symptomatic late-onset hypogonadism with transdermal testosterone gel.

For over 50 years, testosterone therapy has been used for the treatment of hypogonadism. In recent years, there has been an increase in the use of testosterone therapy for men with late-onset hypogonadism, as more convenient and effective modes of application are developed. Testosterone therapy in these men can significantly improve their sense of well-being, and lead to increases in muscle and bone mass, upper body strength, virility and libido [Gruenewald, Matsumoto. J Am Geriatr Soc 2003;51:101; Morales. Aging Male 2004; in press]. However, ensuring that optimal testosterone therapy is achieved in men with hypogonadism remains challenging. Oral delivery of unmodified testosterone is not possible, due to rapid first-pass metabolism and its short half-life. Therefore, different derivatives and formulations of testosterone have been developed to enhance potency, prolong duration of action or improve bioavailability. In addition, several different routes of administration have now been evaluated, including intramuscular injections, oral formulations, transdermal patches, transbuccal systems and transdermal testosterone gel. Despite the broad range of testosterone therapy on offer, each form has its benefits and limitations, and some will suit one patient more than another. An important concern among clinicians is that testosterone therapy may cause or promote prostate cancer. While current evidence supports the safety of testosterone therapy, androgens are growth factors for pre-existing prostate cancer. Therefore, before therapy is initiated, careful digital rectal examination and determination of prostate-specific antigen (PSA) in serum should be performed, in order to exclude evident or suspected prostate cancer. The first 3-6 months after initiating testosterone therapy is the most critical time for monitoring effects on the prostate. Therefore, it is important to monitor PSA levels every 3 months for the first year of treatment; thereafter, regular monitoring (mostly for prostate safety but also for cardiovascular and haematological safety) during therapy is mandatory.

Vaginal administration of oral micronized estradiol results in successful twin pregnancy in a functionally agonadal woman.

CASE REPORT: A 31-year-old nulligravid woman seeking fertility treatment with in vitro fertilization and intracytoplasmic sperm injection failed to achieve pregnancy. Supernumerary embryos were cryopreserved for future use. In preparation for the transfer of the frozen embryos, the patient was prescribed hormones, which included pituitary down-regulation with leuprolide acetate, followed by oral micronized estradiol (E2) and vaginal progesterone (P4) suppositories. At the time of embryo transfer (ET) it was noted that the patient had misunderstood her instructions and was administering both her estrogen and progesterone vaginally. Ultrasound examination revealed a well-developed endometrium adequate for ET so the procedure was performed, and at that point she was instructed to use E2 orally as originally prescribed. Two weeks later, her beta-hCG was elevated, and subsequent ultrasound examinations revealed a twin gestation. The pregnancy progressed normally. CONCLUSION: This patient's hormones were adequately replaced despite vaginal placement of oral medication. Although not commonly prescribed, oral E2 tablets may be administered vaginally in functionally agonadal women preparing for ET, and may serve as an alternative route for women who experience difficulties with oral formulations.