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The aggressive use of multiple therapeutic modalities has led to a significant increase in the number of survivors of childhood malignancy. Abnormalities of linear growth, thyroid function and sexual development are encountered often in children and adolescents following the successful treatment of brain tumours.
An endometrial carcinoma developing in a patient with pure Turner's syndrome was described. The patient showed typical Turner's phenotype and analysis of karyotype revealed only 45,X. Secondary sexual development had been seen until age 20 and she had no history of hormone replacement therapy (HRT). The enlarged uterus and normal appearance of bilateral ovaries were detected at laparotomy. A well-differentiated adenocarcinoma of the endometrium and a graafian follicle of the left ovary were histologically confirmed. This seems to be the first report of the occurrence of endometrial carcinoma in possibly pure Turner's syndrome without HRT.
Androgens play a crucial role in the development of male reproductive organs such as the epididymis, vas deferens, seminal vesicle, prostate and the penis. Furthermore, androgens are needed for puberty, male fertility and male sexual function. High levels of intratesticular testosterone, secreted by the leydig cells, are necessary for spermatogenesis. Intratesticular testosterone is mainly bound to androgen binding protein and secreted into the seminiferous tubules. Inside the sertoli cells, testosterone is selectively bound to the androgen receptor and activation of the receptor will result in initiation and maintenance of the spermatogenic process and inhibition of germ cell apoptosis. The androgen receptor is found in all male reproductive organs and can be stimulated by either testosterone or its more potential metabolite dihydrotestosterone. Severe defects of the androgen receptor may result in abnormal male sexual development. More subtle modulations can be a potential cause of male infertility. Treatment of an infertile man with testosterone does improve spermatogenesis, since exogenous administrated testosterone and its metabolite estrogen will suppress both GnRH production by the hypothalamus and Luteinising hormone production by the pituitary gland and subsequently suppress testicular testosterone production. Also, high levels of testosterone are needed inside the testis and this can never be accomplished by oral or parenteral administration of androgens. Suppression of testosterone production by the leydig cells will result in a deficient spermatogenesis, as can be seen in men taking anabolic-androgenic steroids. Suppression of spermatogenesis by testosterone administration is also the basis for the development of a male contraceptive. During cytotoxic treatment or irradiation suppression of intratesticular testosterone production cells may prevent irreversible damage to the spermotogonial stem cells.
Plasma levels of prolactin (PRL) and luteinizing hormone (LH) were determined in pinealectomized (PX) and/or bilateral ocular enucleated (EX) turkey hens and toms during gonadal development. Measurements were obtained weekly for 6 weeks following photo-induced ovarian recrudescence in adult hens and biweekly from 12 to 34 weeks of age in sexually developing toms. Both hens and toms were maintained on a photoperiod of 16L:8D. Plasma PRL levels were significantly correlated with time (P less than 0.01) and were linear with significant slopes (P less than 0.01) in all treatment groups of hens and toms. However, the regression coefficients were positive for the hens and negative for the toms. Both PX and EX reduced PRL levels in the hens. PX did not significantly affect PRL levels of toms but EX depressed PRL levels. In hens LH was not correlated with weeks of photostimulation but in toms LH was positively correlated to age and linear with significant slopes in all treatment groups. There were no significant treatment effects on plasma LH levels of hens or toms. It was concluded that neither the pineal gland nor the eyes affect plasma LH levels of male turkeys during testicular development or female turkeys during photostimulated ovarian recrudescence. Although the eyes affected plasma PRL of both males and females during gonadal development, the pineal only influenced female PRL levels.
Serum and testicular concentrations of testosterone were determined by radioimmunoassay in four prepubertal patients (Tanner's genital stage G1) with unilateral cryptorchidism and in ten pubertal patients with different degrees of genital development (stages G2-G5), five with unilateral and five with bilateral cryptorchidism. In every case, testicular testosterone concentration was determined in the cryptorchid gonad. Two prepubertal autopsy cases were also studied. Results were compared with scrotal testes of adult subjects. Pubertal development resulted in a gradual increase in tubule diameter on microscopic examination notwithstanding the abnormal position of the gonad. As expected, serum testosterone also increased gradually throughout sexual development. Testicular testosterone concentration however increased to adult levels at early stages of puberty. Mean concentrations and ranges were: G1, 26 ng/g (range 7-49, n = 6); G2 + G3, 660 (range 37-1357, n = 6); G4 + G5, 438 (range 272-702, n = 4) and adults 520 (range 356-663, n = 4). This resulted in similar testicular: serum testosterone ratios in G1, G4 + G5 and adults but a high ratio in G2 + G3. Patients of groups G2 + G3 did not have elevation of serum gonadotrophins and did not show Leydig cell hyperplasia. Therefore, in early puberty, when peripheral tissues are exposed to low testosterone levels, seminiferous tubules of cryptorchid gonads might already receive high androgen stimulation.
A reduced GH secretion has often been shown in prepubertal children with delays in pubertal development. In order to study the mechanism underlying this finding, we evaluated peripheral circulating levels of GH, GHRH, and somatostatin (SRIH) before and after the onset of sexual development in a group of eight late maturing children (six boys, two girls), comparing the results with those obtained in two groups of five prepubertal and four pubertal short children with familial short stature. GH was measured by a two-site immunoradiometric assay. Both GHRH and SRIH were assayed by specific RIAs after an acetone-petrolether extraction from plasma. Our data showed a significant increase (P less than 0.001) in GH, GHRH, and SRIH levels (peak vs. basal values) in response to L-dopa administration in all groups. In pubertal children with delays in pubertal development GH and GHRH peak values (15.8 +/- 2.2 micrograms/L and 120 +/- 18 pg/mL, respectively) were significantly greater (P less than 0.001) than in the same subjects before puberty (8.2 +/- 0.9 micrograms/L and 79 +/- 9 pg/mL, respectively), whereas SRIH peak values did not significantly change (41 +/- 6 vs. 41 +/- 5 pg/mL; P = NS). Furthermore, prepubertal subjects with delays in pubertal development showed GH and GHRH peak values lower (P less than 0.001) than those of prepubertal subjects with FSS (13.3 +/- 1.8 micrograms/L and 120 +/- 13 pg/mL, respectively), whereas no statistical difference was present between the two groups of subjects after pubertal development (18.2 +/- 2.9 micrograms/L and 128 +/- 11 pg/mL, respectively). In conclusion, these findings support the assumption that in late maturing subjects during prepubertal period the decreased GH secretion may be ascribed to a reduced GHRH secretion, reversible with the onset of puberty, without change in circulating SRIH levels.
Male rhesus monkeys secrete adult levels of androgen for 3 months postnatally. The role of this neonatal testicular secretion in sexual development was investigated by suppressing luteinizing hormone (LH) and testosterone (T) in neonatal male rhesus (n = 6) by administering a gonadotropin-releasing hormone agonist (Ag) for the first 4 months of postnatal life. Controls (n = 4) received vehicle. Six years later, endocrine function and sexual behavior were examined with ovariectomized females (n = 6) receiving periodic estradiol (E2) treatment during the breeding and nonbreeding seasons. During the breeding season, there were no differences between Ag-treated and control males in levels of LH and T or in frequency of copulatory behavior. However, Ag-treated males masturbated less frequently than controls when the females were not on E2. During the nonbreeding season, Ag-treated males had lower T levels than controls when the females were not receiving E2 and copulated less when the females received E2, even though T levels were comparable. During both E2 and non-E2 treatments, Ag-treated males secreted less T per unit of LH than controls. Neonatal Ag treatment had no effect on social rank. These data demonstrate that neonatal testicular suppression, or the Ag treatment itself, altered systems regulating sexual motivation and neuroendocrine control of these males and suggest that the early neonatal period in male rhesus monkeys is another point when the developing central nervous system is sensitive to the organizing actions of androgens.
Turner's Syndrome [TS] is a chromosomal disorder that affects one in 2500 women. It results in an array of physical difficulties, including short stature, lack of secondary sexual development and cognitive problems. Little research exists to document the psychosocial problems and needs of individuals with TS and their families. The current literature and the results of a regionally based needs assessment are reviewed to guide program development, with emphasis on the emotional and informational needs of these families. Suggestions are provided for strategic early communication and information sharing, development of skill-specific support groups, family networks and family therapy.
Between 20% and 25% of the patients seeing a doctor have sexual problems. These have various causes: somatopsychological, psychosomatic, social-somatic and psychological factors can play an important role. For an effective therapy, a biopsychosocial understanding of the development of these diseases is necessary. Tumor-patients belong to a special group who frequently develop sexual problems. There are many patients with prostate cancer who, after a radical prostatectomy, suffer from erectile dysfunction. As sexuality always has a social dimension, there is no sexual dysfunction which can be seen as separate from partnership and social environment. Hence the couple is the patient, not the malfunctioning penis. Sexual rehabilitation's main aim is therefore not the repair the malfunctioning organ but rather the improvement of the quality of the sexual relationship beyond penetration.
There is little available on HIV-positive women's sexual relationships other than within-risk behavior paradigms. Increased life expectancy with the advent of highly active antiretroviral therapies (HAART) may increase the opportunity for women to develop sexual relationships. This study investigates sexual functioning in HIV-positive women and presents the analysis of interviews with 21 seropositive heterosexual women (age range, 22-54). Fourteen (67%) were black African, 6 (29%) white European, and 1 (5%) "other." Thirteen (62%) were currently or had been sexually active since becoming aware of their diagnosis. Dominant themes identified included: (1) difficulties with sexual functioning, in particular lowered libido and enjoyment and reduced intimacy; (2) barriers to forming new relationships: fears of HIV disclosure, fears of infecting partners; (3) coping strategies: included relationship avoidance and having casual partners to avoid disclosure; (4) safer sex: personal dislike of condoms, lack of control, lack of suitable alternatives. Women are experiencing a range of sexual and relationship difficulties that appear to be relatively unchanged despite the advent of HAART. Culturally appropriate, focused psychosexual and couples work should be more readily available for women living with HIV and their partners.
46XY gonadal dysgenesis is a rare condition of intersexuality first described in detail by Swyer in 1955. It is characterized by a phenotypic female who is tall, eunuchoid with normal female external genitalia, hypoplastic uterus and Fallopian tubes, streak ovaries and primary amenorrhoea. The patients exhibit none of the associated congenital defects such as webbing of the neck and genu valgum seen in Turner's syndrome. Although rare, this clinical entity is important to recognize because of the high incidence of gonadoblastomas and subsequent development of dysgerminoma. The condition may be familial and therefore siblings need to be screened. To the geneticists and scientists researching in the area of intersexuality, hermaphroditism and sexual determination, it has helped to unveil the mechanisms of gonadal and genital sexual development.
A case of a 9-year-old boy with neurofibromatosis of von Recklinghausen and precocious puberty is reported. The patient was referred to us because of an unexplained onset of precocious puberty. Clinical manifestations of neurofibromatosis included multiple café-au-lait spots, skeletal anomalies, progressive impairment of vision and precocious sexual development. CT scan and NMR demonstrated the presence of optic gliomas. The correlation between the lesions of retino-hypothalamic projection and production of the neuroendocrinology mechanism of sexual changes is discussed.
Growing pullets were maintained on 14-h photoperiods and given diets supplemented with 25 mg of melatonin (MEL)/kg during the final 7 h of the photo-period to investigate the role of MEL in sexual development. Melatonin diets were fed to 70 d (to mimic a transfer from 7 to 14 h at 70 d), from 105 d onward (to mimic a transfer from 14 to 7 h at 105 d), or throughout the trial (to mimic constant 7-h photoperiods). Control birds, which were fed normal diets, were maintained on 7 or 14 h, transferred from 7 to 14 h at 70 d, or transferred from 14 to 7 h at 105 d. The MEL groups matured 6 to 11 d later than the constant 14-h controls. The group mimicking a transfer from 7 to 14 h matured 35 d later than photostimulated controls, the group mimicking a 14 to 7-h change at 105 d matured 41 d earlier than birds given a decrease in day length; the third group matured 13 d earlier than constant 7-h controls. Although these data suggest that the birds did not perceive the final 7 h of the photoperiod as being part of the night, when given MEL diets, residual plasma MEL during the first 7 h of the photoperiod was atypically high, possibly preventing an interpretation of day and night. However, continuously high plasma MEL did not result in birds responding as if in constant darkness, because birds transferred from darkness to 14 h at 70 d would not have matured at a similar time to birds changed from 14 h to darkness at 105 d. Plasma LH concentrations for birds mimicking a 7 to 14 h change at 70 d were not significantly different from constant 7-h controls after the transfer to normal diets. The later maturity of the experimental groups, compared with constant 14-h controls, clearly indicated that MEL had some influence over hypothalamic activity and gonadal development.
Communication between parents and adolescents about adolescents' sexual behavior has been studied. However, the types of issues on which adolescents are willing to communicate with their parents have been scarcely discussed. A survey was conducted among a random sample of 1,204 junior high school students in Taipei. The survey probed into adolescents' communication with their parents as related to sex, including physical development, sexuality, choice of partner, frequency of dating, whom to date, and intimacy during dating. Analysis showed that physical development was the topic most often discussed. Talking about dating was discussed less than the other three topics. Moreover, girls were more likely to communicate with their parents than boys about all six issues.
Cimetidine has been reported to cause antiandrogenic effects in male pups of female rats receiving cimetidine during gestation. Because of conflicting reports of cimetidine causing permanent antiandrogenic effects in male rats, we studied the sexual development of male rats born to females receiving cimetidine. Water or water and cimetidine (194 mg/kg of body weight per day) were administered to pregnant rats from day 12 of gestation through weaning. A total of 130 male pups were studied. Testicular prostate gland/seminal vesicle weights, anogenital distance, serum testosterone and dihydrotestosterone levels, and seminiferous tubule areas were compared between the two groups. Transfer of cimetidine across the placenta and though breast milk was confirmed by HPLC analysis of serum from female littermates at 0, 10, and 20 days of age. With the exception of a smaller anogenital distance (p < 0.03) and a lower anogenital index (p < 0.05) in the cimetidine-exposed newborn rats, no statistically significant differences were observed in the measured parameters between the cimetidine-exposed and control groups. Cimetidine exposure during the fetal and perinatal periods did not alter the development of secondary sex characteristics in male rat pups.
The decision of the bi-potential gonad to develop into either a testis or ovary is determined by the presence or absence of the Sex-determining Region gene on the Y chromosome (SRY). Since its discovery, almost 13 years ago, the molecular role that SRY plays in initiating the male sexual development cascade has proven difficult to ascertain. While biochemical studies of clinical mutants and mouse genetic models have helped in our understanding of SRY function, no direct downstream targets of SRY have yet been identified. There are, however, a number of other genes of equal importance in determining sexual phenotype, expressed before and after expression of SRY. Of these, one has proven of central importance to mammals and vertebrates, SOX9. This review describes our current knowledge of SRY and SOX9 structure and function in the light of recent key developments.
Treatment of serotonin reuptake inhibitors (SRIs) is associated with sexual dysfunction. The cause of this dysfunction is unclear but may be related to stimulation of the serotonergic system. In the present article, we describe seven patients in whom iatrogenic sexual dysfunction induced by SRIs was treated with cyproheptadine, a 5HT-2 antagonist with antihistaminergic and adrenolytic properties. Seven obsessive-compulsive male patients, aged 29-54 years, who developed sexual dysfunction following treatment with SRIs (fluoxetine, fluvoxamine, and clomipramine) were instructed to take cyproheptadine (4-12 mg) 1-2 h before commencing sexual activity. Five of the seven patients displayed improvement in sexual function, although the improvement was transitory in two. The two remaining patients did not respond. All patients exhibited sedation on the day following cyproheptadine administration. Our preliminary observation suggests that some patients with sexual dysfunction associated with SRI treatment, mainly decreased libido and anorgasmia, may benefit from cyproheptadine administration. The role of 5HT-2 antagonists in SRI-induced sexual dysfunction merits further investigation.
Sexually transmitted diseases common in the adolescent population are associated with significant acute morbidity, complications, and long-term sequelae. Clinicians have the opportunity to play a unique and important role in the control of STD rates among adolescents. Not only are clinicians in a position to routinely discuss healthy sexual development, decision making, and primary STD prevention, they are also in a position to effectively diagnose and manage STDs among both asymptomatic and symptomatic adolescents. Addressing issues related to sexuality and STDs in a consistent and repetitive manner during routine visits will likely increase physician proficiency in this important area of clinical care of adolescents, as well as increase adolescents' recognition of the clinician as a valuable resource.