[Transsexualism. III. The second diagnostic phase: the real-life test].
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Adolescent↗
Biomedical subjects
L J Gooren
Publications and source records attributed to L J Gooren.
Pulsatile secretory patterns of luteinizing hormone in two patients with secondary amenorrhea suffering from Cushing's disease, before and after transsphenoidal adenectomy.
In two infertile women with Cushing's disease, LH pulse frequency increased after pituitary adenectomy; both conceived within 4 months. This finding suggests that defective LH-RH-stimulation of LH secretion accounted (partially) for their infertility.
Activity Cycles↗
The human hypothalamus in relation to gender and sexual orientation.
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Aging↗
Patterns of serum cortisol levels in ovariectomized females with and without androgen administration.
Serum cortisol levels in humans and primates display a circadian rhythm. A study in monkeys showed that orchiectomy abolishes this circadian rhythm. The present study compared the patterns of serum cortisol levels between 9 a. m. and 3 p. m. in two groups of ovariectomized females, one treated with testosterone (T) and one without sex steroid administration. Over the first 80 minutes of the sampling period cortisol levels declined similarly in both groups, probably due to waning of stress of the experiment. Thereafter, levels fell further in the T-administered group, but not in the group without sex steroid administration. From this pilot study it is tentatively concluded that ovariectomy, in analogy with orchiectomy in monkeys, produces a loss of a circadian pattern of cortisol levels, which is reversed by administration of T. Furthermore, upon comparison of mean serum cortisol levels in the two groups, T appeared to have a suppressive effect on values of serum cortisol levels.
Adult↗
17 beta-Oestradiol, androstenedione and inhibin levels in fluid from individual follicles of normal and polycystic ovaries, and in ovaries from androgen treated female to male transsexuals.
OBJECTIVE: The aim was to monitor carefully follicular growth arrest in polycystic ovaries by assay of hormones in individual follicles. DESIGN AND PATIENTS: Fluid from follicles less than or equal to 10 mm was obtained from ovaries of 16 regularly cycling women between days 1 and 12 of the follicular phase (controls, n = 120 follicles), polycystic ovaries of five women with polycystic ovary syndrome (n = 43), and polycystic ovaries from 14 long-term testosterone treated female to male transsexuals (n = 120). MEASUREMENTS: Fluid was assayed for oestradiol, androstenedione, and immunoactive inhibin. Luteinizing hormone, follicle-stimulating hormone, and testosterone levels were estimated in serum. RESULTS: Median serum LH was lower in transsexuals than in controls (P less than 0.05), and in polycystic ovary syndrome (P less than 0.01). Median serum testosterone was not significantly different between polycystic ovary syndrome and transsexuals, and was elevated in both groups as compared to controls (P less than 0.01). Oestradiol was present in all follicles obtained from polycystic ovaries of polycystic and transsexual patients, in which no follicle greater than 10 mm could be detected. In the three groups, between-patient differences in mean oestradiol, androstenedione, inhibin, and androstenedione/oestradiol ratio were significantly larger than expected in view of the variation between follicles within individuals. Taking into account this between-patient difference, no significant differences could be established between the three groups for all endocrine parameters. The percentage of presumed healthy follicles (androstenedione/oestradiol ratio less than or equal to 4) was 12% in controls, 17% in polycystics, and 14% in transsexuals, and was not significantly different between groups. CONCLUSIONS: The results may indicate that (1) abnormally high circulating androgen concentrations with or without elevated LH levels disturb the process of selection, and could therefore play a role in the pathogenesis of polycystic ovaries; (2) in polycystic ovaries from polycystic ovary syndrome and transsexual patients, aromatase activity is present in vivo in small antral follicles, and the proportion of presumed healthy follicles is not different from that encountered in normal ovaries; (3) oestradiol levels are not different between non-dominant follicles of normal and polycystic ovaries, suggesting that only enhancement of aromatase activity by FSH may be disrupted in polycystic ovaries, (4) because androstenedione levels are not different comparing follicles of normal and polycystic ovaries, hyperandrogenaemia in the syndrome seems to originate from the abnormally high number of cystic atretic follicles generally observed in polycystic ovaries; (5) marked variation in the endocrine follicular microenvironment within and between-women precludes pooling fluid from several follicles.
Adult↗
Gender and sexual orientation in relation to hypothalamic structures.
Animal experiments have provided evidence for the presence of sex differences from the synaptic level up to behaviour. Although sex differences in the human brain may have been presumed implicitly since the days of Aristotle, research on the presence of functional and structural sex differences of the human brain started only relatively recently. The most conspicuous sex difference in the mammalian brain was described by Gorski et al. [1978] in the preoptic area (POA) of the rat hypothalamus. We found that the volume of a putative homologue of this sexually dimorphic nucleus (SDN) in the adult human hypothalamus was more than twice as large in men as in women and contained about twice as many cells. Recently a similar sex difference and volume has been described for the human bed nucleus of the stria terminalis and 'interstitial nuclei of the hypothalamus' (INAH). Sexual differentiation of the hypothalamus was generally believed to take place between 4 and 7 months of gestation. A life span study on the SDN of more than 100 subjects revealed, however, that only after the age of 2-4 years postnatally sexual differentiation becomes manifest by a decrease in volume and cell number in the female SDN. If sexual differentiation of the brain indeed takes place postnatally, not only chemical and hormonal factors may influence this process but also social factors. A prominent theory on the development of sexual orientation is that it develops as a result of an interaction between the developing brain and sex hormones. According to Dörner's hypothesis, male homosexuals have a female differentiation of the hypothalamus. This hypothesis was not supported by our observations on the SDN. Neither the SDN volume nor the cell number in the hypothalamus of homosexual men differed from that of heterosexual men. However, a difference in SCN cell number was observed in relation to sexual orientation. The volume and cell number of the SCN of homosexual men was twice as large as that of a reference group. During development, the SCN volume and cell counts reach peak values around 13-16 months after birth. At this age the SCN contains about the same number of cells as the SCN of adult male homosexuals, whereas in the reference group the cell numbers subsequently decline to the adult value, which is about 35% of the peak value.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
The effect of 6 weeks of testosterone treatment on pulsatile luteinizing hormone secretion in eugonadal female-to-male transsexuals.
Polycystic ovary disease generally is associated with elevated androgen levels and elevated luteinizing hormone (LH) levels, whereas follicle-stimulating hormone (FSH) levels are (sub)normal. To assess the role of androgens on gonadotropin secretion, we investigated the effect of 6 weeks of testosterone (T) undecanoate, 120 to 160 mg/d orally, on the parameters of the pulsatile secretion of LH in a group of six eugonadal female-to-male transsexuals with normal menstrual cycles. The treatment suppressed menstrual activity in all patients. Serum T and estrone were significantly elevated after treatment with oral T undecanoate. The parameters of the pulsatile secretion of LH were not affected by androgen administration. Levels of FSH, estradiol, and progesterone also did not change significantly.
Estrone↗
Ovarian morphology in long-term androgen-treated female to male transsexuals. A human model for the study of polycystic ovarian syndrome?
Descriptions of the effect of androgens on ovarian human tissues are exceptional. This opportunity was provided for us by 17 women with transsexualism--female to male transsexuals (TSX)--who had been given androgens for a mean period of 21 months before hystero-salpingo-oophorectomy took place. Twenty-nine ovaries from TSX and 14 control ovaries from 13 regularly cycling women were examined. As compared with controls, TSX ovaries were enlarged and displayed a two-fold increase in cystic follicles and a 3.5-fold increase in atretic follicles; the ovarian cortex was collagenized and three-times thicker. Theca interna hyperplasia and luteinization were uniformly observed in TSX cystic follicles. Stromal hyperplasia was a constant finding in TSX ovaries, accompanied by clusters of luteinized stromal cells in 12 cases. Eventually, these findings met the histological criteria for the diagnosis of polycystic ovaries. These observations demonstrate that androgens alone may induce polycystic changes. The assumption that the role of androgens is pivotal at the follicular level--inducing follicle growth arrest and accelerating cystic changes--in the genesis of polycystic ovaries is reinforced.
Adolescent↗
[Use and abuse of androgens; side effects and risks].
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Anabolic Agents↗
Effects of the pure antiandrogen RU 23.903 (anandron) on sexuality, aggression, and mood in male-to-female transsexuals.
Sexuality, aggression, and mood were investigated in 14 presurgical male-to-female transsexuals, undergoing antiandrogenic treatment with anandron, a pure antiandrogen. Subjects were given a test battery the morning prior to treatment onset and after 8 weeks of treatment. In addition they were requested to complete daily forms concerned with sexual behavior and mood. Morning erections and the frequency of thoughts and fantasies about sex decreased after anandron intake. Aggressive feelings were uncorrelated with testosterone level. Moods such as level of energy, feelings of relaxation, fatigue, and feelings of tension and anxiety appeared to fluctuate more as a consequence of anandron intake than did moods such as cheerful, sociable and friendly, gloomy and unhappy, irritated and changeable. The latter remained at a constant level.
Adult↗
Mortality and morbidity in transsexual patients with cross-gender hormone treatment.
Sex steroid treatment is associated with side effects. The number of deaths and morbidity cases in 425 transsexual patients treated with cross-gender hormones were evaluated retrospectively and compared with the expected number in a similar reference group of the population. The number of deaths in male-to-female transsexuals was five times the number expected, due to increased numbers of suicide and death of unknown cause. Combined treatment with estrogen and cyproterone acetate in 303 male-to-female transsexuals was associated with a 45-fold increase of thromboembolic events, hyperprolactinemia (400-fold), depressive mood changes (15-fold), and transient elevation of liver enzymes. Androgen treatment in 122 female-to-male transsexuals was associated with weight increase greater than 10% (17.2%) and acne (12.3%). In both groups persistent liver enzyme abnormalities could be attributed to other causes than sex steroids (hepatitis B and alcohol abuse). Much of the morbidity was minor and reversible with appropriate treatment or temporary discontinuation of hormone treatment. Thus, the dilemma of prescribing cross gender hormones in view of the needs of these patients is not resolved. Explanation of possible side effects and careful clinical judgment remain the cornerstone of the clinical decision to prescribe cross-gender hormones. Furthermore, follow up of this relatively young population to disclose long-term side effects and to elucidate the association of sex steroids with coronary heart disease, as well as efforts to reduce the risk of thromboembolic events, are required.
Adolescent↗
Pulsatile luteinizing hormone release and ovarian steroid levels in female-to-male transsexuals compared to heterosexual women.
It has been suggested that there is a difference in the interaction between sex steroids and gonadotropin secretion between transsexual and heterosexual women. In this study we tested whether there is a difference in the pulsatile release characteristics of luteinizing hormone (LH) and in ovarian steroid concentrations between 16 female-to-male (f-to-m) transsexuals and eight eugonadal heterosexual women during the early follicular phase of the menstrual cycle. Blood samples for LH determination were collected every 10 min for 7 hr in the transsexual group, and every 10 min for 6 hr in the heterosexual group. There were no significant differences between the transsexual and heterosexual group in mean serum LH concentration (6.9 +/- 2.4 U/l vs. 7.5 +/- 2.6 U/l), mean LH nadir interval (77 +/- 37 min vs. 70 +/- 16 min), and mean LH pulse amplitude (2.9 +/- 1.1 U/l vs. 3.0 +/- 1.1 U/l). Serum estrone, 17-beta-estradiol, testosterone, progesterone and FSH concentrations also did not differ between the two groups. There also was not a higher prevalence of polycystic ovarian disease in our f-to-m transsexual group than in the general population.
Adult↗
Reduction in undesired sexual hair growth with anandron in male-to-female transsexuals--experiences with a novel androgen receptor blocker.
The effect of Anandron, a novel non-steroidal anti-androgen, on the reduction in sexual hair growth of 14 male-to-female transsexuals was investigated. Anandron (300 mg/day) alone for 8 weeks increased serum testosterone levels (mean: 19.2 +/- 6.1 to 44.9 +/- 11.5 mmol/l) and serum oestradiol levels (mean: 0.08 +/- 0.02 to 0.24 +/- 0.06 nmol/l). From Weeks 9 to 20, ethinyloestradiol (100 micrograms/day) was co-administered. Hair growth scores, hair weight and the number of terminal hairs decreased significantly in the first 8 weeks and continued to decrease during the second period in the areas assessed (the trunk and the limbs). In addition, there was a subjective decrease in hair growth on the limbs and the trunk, but not on the face. We suggest that Anandron alone and in conjunction with oestrogens is effective in reducing sexual hair growth on the limbs and the trunk.
Adult↗
Effects of long-term testosterone administration on gonadotropin secretion in agonadal female to male transsexuals compared with hypogonadal and normal women.
We investigated the effects of long term testosterone (T) administration on pulsatile gonadotropin secretion in agonadal women and the effects of estradiol (E2) on gonadotropin secretion in eugonadal women in the follicular phase of the menstrual cycle. We studied 4 groups: A) 28 eugonadal women in the early follicular phase of the menstrual cycle, B) 11 hypogonadal women, C) 13 agonadal female to male (f-t-m) transsexuals treated for at least 3 months with 120-160 mg T undecanoate (TU)/day, orally, and D) 5 agonadal f-to-m transsexuals treated for at least 6 months with 250 mg of a mixture of testosterone esters, im (im T-esters), every 2 weeks. The eugonadal women in the early follicular phase had a mean serum E2 level of 193 +/- 94 (+/- SD) pmol/L, significantly higher (P less than 0.01) than that in the hypogonadal women (60 +/- 24 pmol/L), whereas there was no difference in the mean serum T levels (1.8 +/- 0.7 vs. 2.3 +/- 1.5 nmol/L). the higher serum E2 level in the eugonadal women was associated with a significantly lower mean serum LH level (6.9 +/- 2.6 vs. 44.6 +/- 17.6 U/L; P less than 0.01) and LH pulse amplitude (2.8 +/- 1.0 vs. 12.6 +/- 4.8 U/L; P less than 0.01), whereas the mean nadir LH interval did not differ between the two groups (75 +/- 29 vs. 81 +/- 49 min). The mean serum T level in the agonadal f-to-m transsexuals treated with oral TU was significantly higher (P less than 0.01) than that in the hypogonadal women (9.7 +/- 4.7 vs. 2.3 +/- 1.5 nmol/L). In spite of this elevated T level there was no difference in the mean serum LH level (38.4 +/- 14.7 vs. 44.6 +/- 17.6 U/L), LH pulse amplitude (14.3 +/- 5.7 vs. 12.6 +/- 4.8 U/L), or nadir LH interval (72 +/- 27 vs. 81 +/- 49 min) in these groups. Also, the mean serum E2 (64 +/- 16 vs. 60 +/- 24 pmol/L and FSH levels (62 +/- 17 vs. 64 +/- 28 U/L) did not differ between these groups. Treatment of the agonadal f-to-m transsexuals with im T-esters resulted in mean serum T and E2 levels of 34.4 +/- 27.0 nmol/L and 121 +/- 54 pmol/L, respectively, both significantly higher (P less than 0.01) than those in groups B and C.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
The effects of long term testosterone administration on pulsatile luteinizing hormone secretion and on ovarian histology in eugonadal female to male transsexual subjects.
Polycystic ovarian disease (PCOD) is associated with elevated serum LH and (sub)normal FSH levels, while serum androgen levels are often elevated. To clarify the role of androgens in this abnormal pattern of gonadotropin secretion, LH secretion was studied in 1) 9 eugonadal female to male transsexual subjects before and during long term (6 months) testosterone (T) administration (250 mg/2 weeks, im), and 2) in a woman with an androgen-secreting ovarian tumor both before and after surgical removal of the tumor. Finally, we studied the effects of high serum androgen levels on ovarian histology in 3) 26 transsexual subjects after long term (9-36 months) T administration (250 mg/2 weeks, im) to assess whether T-induced ovarian abnormalities are similar to those that occur in women with PCOD. Long term T treatment in the nine female to male transsexual subjects resulted in increases in the mean serum T level from 1.7 +/- 0.8 (+/- SD) to 40.8 +/- 31.9 nmol/L (P less than 0.01), the mean serum dihydrotestosterone level from 0.6 +/- 0.2 to 3.3 +/- 1.5 nmol/L (P less than 0.02), and the mean serum free T level from 9.5 +/- 5.2 to 149 +/- 46 pmol/L (P less than 0.02). Mean serum estrone and estradiol levels were similar before and during T treatment. The mean serum LH level decreased from 6.3 +/- 2.0 to 2.9 +/- 1.1 U/L (P less than 0.01), and the mean FSH levels decreased from 6.6 +/- 2.0 to 3.7 +/- 2.2 U/L (P less than 0.02). Pulsatile LH secretion before and during T treatment was studied in five subjects. Neither the mean nadir LH interval nor the LH pulse amplitude changed significantly in these five subjects. The serum T level in the woman with the androgen-secreting ovarian tumor was 9.6 nmol/L, and it declined to normal after removal of the tumor. Her mean serum LH and FSH levels, the mean nadir LH interval, and LH pulse amplitude were in the normal range before and after removal of the tumor. Studies of ovarian histopathology in 26 transsexual subjects after long term androgen treatment revealed multiple cystic follicles in 18 subjects (69.2%), diffuse ovarian stromal hyperplasia in 21 subjects (80.8%), collagenization of the tunica albuginea in 25 subjects (96.2%), and luteinization of stromal cells in 7 subjects (26.9%). Findings consistent with criteria for the pathological diagnosis of polycystic ovaries, that is 3 of the 4 findings listed above, were present in 18 of the 26 subjects (69.2%).(ABSTRACT TRUNCATED AT 400 WORDS)
Androgens↗
Termination of early pregnancy by the 3 beta-hydroxysteroid dehydrogenase inhibitor epostane.
Progesterone is essential to sustain pregnancy in the first eight weeks. Its synthesis requires the enzyme 3 beta-hydroxysteroid dehydrogenase (3-HSD). We tested the efficacy of an orally administered 3-HSD inhibitor, epostane, in terminating unwanted early pregnancy. Fifty women in the fifth through eight weeks of pregnancy took epostane (200 mg orally every six hours) for seven days. By day 14, pregnancy had been terminated in 42 of the 50 patients (84 percent). Eight women (16 percent) did not abort and underwent dilation and curettage. Vaginal blood loss occurred on average on the third day of epostane treatment, and abortion on the fifth day. Two patients had incomplete abortions; one required a transfusion because of blood loss. Nausea was frequent (in 86 percent), but 76 percent of the participants concluded that epostane was preferable to dilation and curettage. The mean (+/- SD) pretreatment progesterone level (76 +/- 16 nmol per liter) decreased by day 7 (to 16 +/- 11 nmol per liter) and day 14 (to 10 +/- 9 nmol per liter) in those who aborted; levels of human chorionic gonadotropin also decreased from the mean at base line (73 +/- 72 kIU per liter) to 18 +/- 7 kIU per liter on day 7 and 9 +/- 5 kIU per liter on day 14. In those who did not abort after epostane treatment, progesterone levels decreased only slightly by day 7 (to 52 +/- 21 nmol per liter) and rose again (to 81 +/- 18 nmol per liter) by day 14. Among women who responded to epostane, normal menstrual periods had resumed by day 42 after the beginning of treatment in 72 percent. We conclude that epostane taken orally is an effective and safe method for the noninvasive termination of undesired early pregnancy.
3-Hydroxysteroid Dehydrogenases↗
Merits and considerations in the use of anti-androgen.
Anandron administration (300 mg/daily) to 16 human normal genetic male volunteers (who opted for male to female gender transformation) induced clinical signs of feminisation during 8 weeks of treatment. More than 2-fold increase in blood luteinising hormone and testosterone was measured while follicle stimulating hormone remained without any change in the levels. Prolactin showed a slight but significant increase at 8 weeks of treatment. The prostate size measured in 6 subjects using transrectal ultrasonography before and at 8 weeks of anandron treatment showed no change. The prostate size measured in 6 subjects who received androcur (100 mg/daily) in combination with ethinyl estradiol (100 micrograms/daily) for longer than 18 months did not differ compared to pre-treatment size. However, the prostate histology showed a clear predominance of stromal components with a significant reduction in the number of acini. The epithelial cells appeared atrophic. Histology of the testes showed a readily observable reduction in tubular and interstitial cells. The monodispersed cells prepared from the testes consisted of Leydig and non-Leydig cells. These cells responded to stimuli (hCG and Pregnenolone) in terms of an increase in testosterone synthesis in vitro. Anandron treatment of intact mature male rats increased the blood testosterone level. Estrogen administration dramatically reduced the anandron induced increase in testosterone to castration level. The benefits of a combination of low doses of anandron and estrogen for achieving an effective anti-androgenic action are presented.
Animals↗
Short-term patterns of pulsatile luteinizing hormone secretion do not differ between male-to-female transsexuals and heterosexual men.
This study tested whether there is a difference in the pulsatile LH secretion between male-to-female transsexuals and eugonadal heterosexual men. The mean serum LH concentrations, the LH pulse frequency, and the LH pulse amplitude were compared between a group of eight male-to-female transsexuals and a group of 22 heterosexual men. Blood samples for LH determinations were collected every 10 min for seven hours. 17-beta-estradiol and testosterone were measured at the beginning of each test. There were no significant differences between the heterosexual and transsexual group in LH pulse frequency (3.9 +/- 1.3 vs. 3.9 +/- 1.7), LH pulse amplitude (3.7 +/- 1.3 U/l vs. 3.0 +/- 0.5 U/l), mean serum LH concentration (5.2 +/- 1.4 U/l vs. 5.4 +/- 1.1 U/l), 17-beta-estradiol (0.07 +/- 0.01 nmol/l vs. 0.08 +/- 0.02 nmol/l), or testosterone (22.9 +/- 3.7 nmol/l vs. 21.8 +/- 8.0 nmol/l). We conclude that the pulsatile release characteristics of LH do not allow a distinction between eugonadal heterosexual men and eugonadal male-to-female transsexuals.
Adult↗