Cross-sex hormone administration changes pain in transsexual women and men

Chronic pain is gender-related, since there is a clear predominance of one sex with respect to the other in most pain syndromes. Gonadal hormones are known to affect the occurrence and incidence of pain. Transsexuals receive cross-sex hormones to develop and maintain somatic characteristics of the opposite sex: male to female transsexuals (MtF) are administered estrogens and anti-androgens, while female to male transsexuals (FtM) are administered androgens. Hence, these subjects represent a model to study the relationship between sex hormones and pain. Questionnaires dealing with sociodemographic data and pain (occurrence, frequency, duration, intensity, location and associated symptoms) were administered to both MtF and FtM transsexuals under hormone treatment for sex reassignment for at least 1 year. Forty-seven MtF and 26 FtM completed the questionnaires. Fourteen of the 47 MtF (29.8%) reported painful conditions, which in 11 subjects were not present before the beginning of hormone treatment. Pain consisted mainly of headaches and breast and musculoskeletal pain. Five subjects suffered from more than one pain condition. Sixteen of the 26 FtM (61.5%) reported pain. In 11 subjects, the pain was present before the beginning of hormone intake, and in 6 of them it improved after testosterone administration. These data suggest that marked changes in sex hormones affect the occurrence of pain in a high percentage of humans but not in all of them. Whether these effects are due to peripheral or central actions of sex steroids is unknown.     

Recent advances in hormonal male contraception

Hormones inhibit fertility in men by suppressing sperm production. Testosterone-enanthate induced azoospermia has proven to provide optimal contraceptive protection. Preliminary studies have shown that testosterone alone or androgen-progestin combinations induce profound sperm suppression in the Eastern and white populations, respectively. Thus, these regimens may represent viable options for male contraception. New long-acting androgen formulations represent a major advancement in this field, allowing for the development of more acceptable and effective regimens.     

Twenty-one day administration of dienogest reversibly suppresses gonadotropins and testosterone in normal men

Androgen-progestin combinations are promising male contraceptive regimens. Optimization of these regimens includes the development of new progestins with more favorable biological properties. In this context we tested the effects of the progestin dienogest (DNG) on reproductive hormones and metabolic parameters in men. After a 3-wk control period, 25 men were randomly assigned to receive daily doses of 2, 5, or 10 mg DNG or placebo and 10 mg cyproterone acetate for 21 d (n = 5 subjects/group). Subjects were followed for 2 wk after cessation of hormone administration. Weekly blood samples, physical examinations, hormone and chemistry measurements, semen analysis, and sexual/behavioral assessments were performed. These parameters were compared among study groups and within each group at different time points throughout the study periods. DNG and cyproterone acetate administration resulted in profound suppression of gonadotropins and T with no change in SHBG levels. No adverse effects were detected in any subject. Hormone levels returned to baseline after stopping hormone intake. DNG is a potent suppressor of gonadotropins and T in men and does not induce adverse effects over a 21-d administration. DNG is a promising progestin to be used in clinical trials for male contraception.     

Endocrine response determines the clinical outcome of pulsatile gonadotropin-releasing hormone ovulation induction in different ovulatory disorders

To accrue systematic information in different ovulatory disorders on the precise relationship among endocrine response, clinical outcome, and the occurrence of complications, we treated 114 patients with pulsatile GnRH (2.5-5.0 micrograms, iv, every 60 min) for 187 cycles and compared them to 20 normal menstrual cycles. Thirty of these patients had primary hypogonadotropic amenorrhea (PHA; 40 cycles), 33 had other forms of hypogonadotropic hypogonadism (HH; 55 cycles), and 51 had polycystic ovary syndrome (PCOS; 92 cycles). Daily blood samples were drawn for hormone determinations. In PCOS, 50 cycles were preceded by GnRH analog suppression. PHA treatment cycles were characterized by the reestablishment of a normal endocrine pattern, almost no dose-related endocrine differences, elevated ovulatory (93%) and conception rates (23%), and no multiple pregnancies. In the HH subjects the ovulatory (91%) and pregnancy rates (31%) were high; however, while the lower GnRH dose elicited a normal endocrine pattern, the 5-micrograms dose induced excessive folliculogenesis and high estradiol levels and was associated with most of the multiple pregnancies of this study (three of four). GnRH analog suppression was successfully used to avoid recurrence of ovarian over-stimulation in two HH subjects. Finally, GnRH analog suppression in PCOS permitted normalization of the follicular phase endocrine pattern, achievement of good ovulatory (76%) and pregnancy (28%) rates, and avoidance of multiple pregnancies; however, luteal phase steroid secretion was abnormal, and the abortion rate remained elevated (43%). Obesity was associated with a reduced ovulatory rate in PCOS, but not in hypogonadotropic, subjects. Thus, we can conclude that in pulsatile GnRH ovulation induction: 1) a profound hypogonadotropic condition, whether spontaneous as in PHA or induced with GnRH analogs as in other ovulatory disorders, is associated with optimal menstrual cycle restoration, high ovulatory and conception rates, and virtually absent risks of multiple pregnancy; 2) residual hypothalamic activity in HH may be responsible for supraphysiological pituitary-ovarian stimulation and result in multiple pregnancy unless a low GnRH dose (2.5 micrograms/bolus) or GnRH analog pretreatment is employed; 3) obesity does not affect treatment outcome in hypogonadotropic patients; and 4) the high spontaneous abortion rate in PCOS may be related to corpus luteum dysfunction.     

A novel circulating hormone of testis origin in humans

Insulin-like factor 3 (INSL3) is a member of the relaxin-insulin family, and it is expressed in pre- and postnatal Leydig cells of the testis. This peptide affects testicular descent during embryonic development, and mutations in INSL3 gene or its receptor LGR8 (leucine-rich repeat-containing G protein-coupled receptor 8)/GREAT (G protein-coupled receptor affecting testicular descent) cause cryptorchidism in humans. The expression of LGR8/GREAT in different tissues and the production of INSL3 also by adult-type Leydig cells suggest additional roles of this hormonal system in adulthood. In this preliminary report we performed the first analysis in humans of INSL3 using a novel RIA kit to measure INSL3 concentrations in serum of normal men and with different testicular pathologies. The results show that INSL3 is circulating in adult men, and it is almost exclusively of testicular origin. Subjects with severe testicular damage, such as men with severe infertility, produce low amount of INSL3, and the concentrations of this hormone seem to reflect the functional status of the Leydig cells. In particular, INSL3 concentrations may be an even more sensitive marker of Leydig cell function than testosterone itself. Analysis of men treated with different combinations of hormones of the hypothalamus-pituitary-testis axis suggests that the production of INSL3 is related to LH in a manner similar to that of the LH-testosterone axis.     

Three-dimensional transvaginal sonography in local staging of cervical carcinoma: description of a novel technique and preliminary results.

OBJECTIVE: To evaluate the feasibility of three-dimensional multiplanar sonography in the local staging of cervical carcinoma. METHODS: Between January 2005 and May 2006, 14 patients with invasive cervical carcinoma underwent transvaginal volume ultrasound examination prior to primary surgery. Parametrial invasion was evaluated in the coronal plane, while both bladder and rectal invasion were evaluated in the sagittal plane. Ultrasound findings were compared with surgical and histological results. RESULTS: In 12 of the 14 cases, three-dimensional ultrasound findings were compatible with pathology results. In the remaining two cases, either infiltration of right parametrium or rectal invasion were suspected at ultrasound but not confirmed at pathology. CONCLUSIONS: Despite the small number of patients evaluated, three-dimensional multiplanar sonography appears to be a promising technique in the local staging of cervical carcinoma.     

Endocrine care of transpeople part II. A review of cross‐sex hormonal treatments,outcomes and adverse effects in transwomen

The treatment of transwomen relies on the combined administration of anti‐androgens or GnRH analogues to suppress androgen production and thereby reduce male phenotypic characteristics together with oestrogens to develop female characteristics. In transwomen, synthetic oestrogens such as ethinyl oestradiol, as well as conjugated equine oestrogens (CEE), should be avoided to minimize thromboembolic risks especially in older transwomen and in those with risk factors. Currently, available short‐ and long‐term safety studies suggest that cross‐sex hormonal therapy (CHT) can be considered safe in transwomen improving the well‐being and quality of life of these individuals. Long‐term monitoring should aim to decrease cardiovascular risks and should include prostate and breast cancer screenings.     

2D and 3D Ultrasound Examination of Labia Minora

The aim of the study was to prospectively evaluate, by using 2D/3D ultrasonography and 3D color Doppler analysis, the morphological and vascular changes in the labia minora during the menstrual cycle of women not sexually aroused. A total of 81 young, healthy eumenorrheic women, in a stable heterosexual relationship (>1 year) and without any sexual dysfunction, underwent 2D/3D ultrasound and color Doppler examination of the labia minora on Days 3–5 and 12–14 of the menstrual cycle. Estradiol serum levels were also evaluated. Estradiol plasma levels increased in the periovulatory phase. The labia minora thickness increased from the follicular (3.8 ± 0.3 mm) to the periovulatory phase (4.6 ± 0.4 mm; p = .005). Furthermore, in the periovulatory phase, the vaginal introitus area and the angles were wider than in the follicular phase. The Pulsatility Index of the posterior labial artery significantly decreased in the periovulatory period. Three-dimensional power Doppler indices of vascularization and blood flow in the labia minora significantly increased in the periovulatory period. The relationship between the different parameters showed that estradiol was positively correlated with labia minora thickness and vaginal introitus area and angles. Furthermore, the circulating levels of estradiol were negatively correlated with posterior labial artery PI and positively correlated with other indices of labia minora vascularization. In conclusion, it seems that estrogen production may influence the anatomic and vascular changes of the labia minora during the menstrual cycle and these changes can be easily identified by ultrasound.     

Gender Identity Disorder and Eating Disorders: Similarities and Differences in Terms of Body Uneasiness

Introduction.Subjects with gender identity disorder (GID) have been reported to be highly dissatisfied with their body, and it has been suggested that the body is their primary source of suffering.Aims.To evaluate quality and intensity of body uneasiness in GID subjects, comparing them with a sample of eating disorder patients and a control group. To detect similarities and differences between subgroups of GID subjects, on the basis of genotypic sex and transitional stage.Methods.Fifty male‐to‐female (MtF) GID (25 without and 25 with genital reassignment surgery performed), 50 female‐to‐male (FtM) GID (28 without and 22 with genital reassignment surgery performed), 88 eating disorder subjects (26 anorexia nervosa, 26 bulimia nervosa, and 36 binge eating disorder), and 107 healthy subjects were evaluated.Main Outcome Measures.Subjects were studied by means of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the Symptom Checklist (SCL‐90), and the Body Uneasiness Test (BUT).Results.GID and controls reported lower psychiatric comorbidity and lower SCL‐90 General Severity Index (GSI) scores than eating disorder subjects. GID MtF without genital reassignment surgery showed the highest BUT values, whereas GID FtM without genital reassignment surgery and eating disorder subjects showed higher values compared with both GID MtF and FtM who underwent genital reassignment surgery and controls. Considering BUT subscales, a different pattern of body uneasiness was observed in GID and eating disorder subjects. GID MtF and FtM without genital reassignment surgery showed the highest BUT GSI/SCL‐90 GSI ratio compared with all the eating disorder groups.Conclusions.GID and eating disorders are characterized by a severe body uneasiness, which represents the core of distress in both conditions. Different dimensions of body uneasiness seem to be involved in GID subsamples, depending on reassignment stage and genotypic sex. In eating disorder subjects body uneasiness is primarily linked to general psychopathology, whereas in GID such a relationship is lacking.     

Current status and future perspectives in male contraception

Contraception is a crucial human right for its role on health, development and quality of life. Since the introduction of hormonal female contraception the burden of family planning has fallen mostly on women. The few methods of family planning available for men--namely condoms, vasectomy, periodic abstinence and withdrawal--are hundred year old in concept, are based on preindustrial practices and have low efficacy or are difficult to reverse. In spite of the shortcomings of currently available male contraceptives, 1/3 of the couples that use contraception worldwide rely on male methods suggesting that development of a safe, effective, reversible and affordable contraceptive method for men would meet a critical need. Recent surveys have shown that men want to know more about reproductive health and want to support their partner more actively. In recent decades, there have been exceptional advances in the development of safer and more effective contraceptives. Currently, several methods of contraception for men are under development. This paper summarises the efforts performed over the past decades to develop an effective, safe and reversible male contraceptive.