Inguinal endometriosis, a rare entity of which surgeons should be aware: clinical aspects and long-term follow-up of nine cases.

INTRODUCTION: Inguinal endometriosis is a rare disease and often misdiagnosed for other, more common groin pathology. We present nine cases of women with inguinal endometriosis with long-term follow-up. METHODS: In this retrospective case series, the Dutch PALGA system was searched for all patients diagnosed with extrapelvic endometriosis located in the groin in the OLVG hospital, Amsterdam, between 2000 and 2016. Relevant information regarding pre- and postoperative characteristics and symptoms was collected. Follow-up consisted of a telephone call from the attending surgeon. RESULTS: None of the patients had a history of pelvic endometriosis. Typically, they presented with a right-sided swelling in the groin. Preoperative ultrasound and MRI were in most cases inconclusive. In one of two patients fna indicated endometriosis. In only three patients the surgeon considered the diagnosis endometriosis preoperatively. Surgical removal was effective with no reported complications. A coexisting hernia sac was resected in four cases, and there was a suspicion of a persistent processus vaginalis (canal of Nuck) in three, suggesting that a persistent processus vaginalis is possibly an important key to the pathogenesis. In none of the cases there was an indication for mesh implantation. One patient was later diagnosed with pelvic endometriosis. CONCLUSION: Follow-up by a gynecologist is advised to check for intra-abdominal disease and inform patients on fertility perspective. Surgeons should be aware of the possibility of inguinal endometriosis in fertile women with a lump in the groin.

Detection of titanium particles in human liver and spleen and possible health implications.

BACKGROUND: Titanium dioxide (TiO2) is produced at high volumes and applied in many consumer and food products. Recent toxicokinetic modelling indicated the potential of TiO2 to accumulate in human liver and spleen upon daily oral exposure, which is not routinely investigated in chronic animal studies. A health risk from nanosized TiO2 particle consumption could not be excluded then. RESULTS: Here we show the first quantification of both total titanium (Ti) and TiO2 particles in 15 post-mortem human livers and spleens. These low-level analyses were enabled by the use of fully validated (single particle) inductively coupled plasma high resolution mass spectrometry ((sp)ICP-HRMS) detection methods for total Ti and TiO2 particles. The presence of TiO2 in the particles in tissues was confirmed by Scanning Electron Microscopy with energy dispersive X-ray spectrometry. CONCLUSIONS: These results prove that TiO2 particles are present in human liver and spleen, with ≥24% of nanosize (< 100 nm). The levels are below the doses regarded as safe in animals, but half are above the dose that is deemed safe for liver damage in humans when taking into account several commonly applied uncertainty factors. With these new and unique human data, we remain with the conclusion that health risks due to oral exposure to TiO2 cannot be excluded.

Misoprostol for cervical priming prior to hysteroscopy in postmenopausal and premenopausal nulliparous women; a multicentre randomised placebo controlled trial.

OBJECTIVE: To evaluate the reduction of pain by misoprostol compared with placebo prior to hysteroscopy in postmenopausal and premenopausal nulliparous women. DESIGN: Randomised multicentre double-blind placebo controlled trial. SETTING: Two Dutch teaching hospitals and one Dutch university medical centre. POPULATION: Postmenopausal and premenopausal nulliparous women undergoing office hysteroscopy. METHODS: Patients were randomised to receive either 400 microgram misoprostol or placebo 12 and 24 hours before hysteroscopy. Pain was quantified by the use of real time pain measurement using the continuous pain score meter (CPSM) and VAS scores. MAIN OUTCOME MEASURES: Primary outcome was pain measured by the CPSM during passage of the hysteroscope through the cervical canal, quantified by the area under the curve (AUC). Secondary outcomes included VAS scores, other CPSM parameters, failures and side effects. RESULTS: In all, 149 patients were randomly assigned to either misoprostol (n = 74) or placebo (n = 75). The AUC during introduction did not significantly differ between the intervention and the placebo group. The VAS score during introduction, however, demonstrated a significant difference in premenopausal nulliparous women favouring misoprostol: 2.9 (95% CI 1.3-4.4) versus placebo 5.5 (95% CI 3.9-7.1), P = 0.02, as well as the AUC during the entire procedure: 618 (95% CI 410-827) versus 1126 (95% CI 671-1580), P = 0.04. Failures were equally distributed between the misoprostol (16%) and placebo group (13%). Intestinal side effects occurred significantly more frequently in the misoprostol group (67%) than in the placebo group (32%) [OR 4.2 (95% CI 2.1-8.3), P < 0.01]. CONCLUSION: Misoprostol prior to hysteroscopy reduces pain in premenopausal nulliparous women but not in postmenopausal women. It does cause side effects. TWEETABLE ABSTRACT: RCT: misoprostol versus placebo prior to hysteroscopy in 149 women significantly reduces some pain parameters.

The HysNiche trial: hysteroscopic resection of uterine caesarean scar defect (niche) in patients with abnormal bleeding, a randomised controlled trial.

BACKGROUND: A caesarean section (CS) can cause a defect or disruption of the myometrium at the site of the uterine scar, called a niche. In recent years, an association between a niche and postmenstrual spotting after a CS has been demonstrated. Hysteroscopic resection of these niches is thought to reduce spotting and menstrual pain. However, there are no randomised trials assessing the effectiveness of a hysteroscopic niche resection. METHODS/DESIGN: We planned a multicentre randomised trial comparing hysteroscopic niche resection to no intervention. We study women with postmenstrual spotting after a CS and a niche with a residual myometrium of at least 3 mm during sonohysterography. After informed consent is obtained, eligible women will be randomly allocated to hysteroscopic resection of the niche or expectant management for 6 months. The primary outcome is the number of days with postmenstrual spotting during one menstrual cycle 6 months after randomisation. Secondary outcomes are menstrual characteristics, menstruation related pain and experienced discomfort due to spotting or menstrual pain, quality of life, patient satisfaction, sexual function, urological symptoms, medical consultations, medication use, complications, lost productivity and medical costs. Measurements will be performed at baseline and at 3 and 6 months after randomisation. A cost-effectiveness analysis will be performed from a societal perspective at 6 months after randomisation. DISCUSSION: This trial will provide insight in the (cost)effectiveness of hysteroscopic resection of a niche versus expectant management in women who have postmenstrual spotting and a niche with sufficient residual myometrium to perform a hysteroscopic niche resection. TRIAL REGISTRATION: Dutch Trial Register NTR3269 . Registered 1 February 2012. ZonMw Grant number 80-82305-97-12030.

Carboxyhaemoglobin formation and ECG changes during hysteroscopic surgery, transurethral prostatectomy and tonsillectomy using bipolar diathermy.

Diathermy is known to produce a mixture of waste products including carbon monoxide. During transcervical hysteroscopic surgery, carbon monoxide might enter the circulation leading to the formation of carboxyhaemoglobin. In 20 patients scheduled for transcervical hysteroscopic resection of myoma or endometrium, carboxyhaemoglobin was measured before and at the end of the surgical procedure, and compared with levels measured in 20 patients during transurethral prostatectomy, and in 20 patients during tonsillectomy. Haemodynamic data, including ST-segment changes, were recorded. Levels of carboxyhaemoglobin increased significantly during hysteroscopic surgery from median (IQR [range]) 1.0% (0.7-1.4 [0.5-4.9])% to 3.5% (2.0-6.1 [1.3-10.3]%, p < 0.001), compared with levels during prostatectomy or tonsillectomy. Significant ST-segment changes were observed in 50% of the patients during hysteroscopic surgery. Significant correlations were observed between the increase in carboxyhaemoglobin and the maximum ST-segment change (ρ = -0.707, p < 0.01), between the increase in carboxyhaemoglobin and intravasation (ρ = 0.625; p < 0.01), and between intravasation and the maximum ST-segment change (ρ = -0.761; p < 0.01). The increased carboxyhaemoglobin levels during hysteroscopic surgery appear to be related to the amount of intravasation and this could potentially be a contributing factor to the observed ST-segment changes.

A personalised eHealth programme reduces the duration until return to work after gynaecological surgery: results of a multicentre randomised trial.

OBJECTIVE: To evaluate the effectiveness of an eHealth intervention on recovery and return to work, after gynaecological surgery. DESIGN: Randomised multicentre trial that ran from March 2010 until September 2011. SETTING: Secondary care in seven general and university hospitals in The Netherlands. POPULATION: A cohort of 215 women (aged 18-65 years) who had a hysterectomy and/or laparoscopic adnexal surgery for a benign indication. METHODS: The women were randomly assigned to the intervention group (n = 110) or the control group (n = 105). The intervention group received an eHealth programme that provided personalised tailor-made pre- and postoperative instructions on the resumption of daily activities, including work, and tools to improve self-empowerment and to identify recovery problems. The control group was provided with access to a control website. MAIN OUTCOME MEASURES: The primary outcome was the duration of sick leave until a full sustainable return to work. Secondary outcome measures were quality of life, general recovery, and pain intensity. RESULTS: In intention-to-treat analysis the eHealth intervention was effective on time to return to work (hazard ratio 1.43; 95% confidence interval 1.003-2.040; P = 0.048). The median duration of sick leave until a full sustainable return to work was 39 days (interquartile range 20-67 days) in the intervention group and 48 days (interquartile range 21-69 days) in the control group. After 26 weeks pain intensity was lower (visual analogue scale, cumulative odds ratio 1.84; 95% confidence interval 1.04-3.25; P = 0.035) and quality of life was higher (Rand-36 health survey, between-group difference 30, 95% confidence interval 4-57; P = 0.024) in the intervention group, compared with the control group. CONCLUSIONS: The use of the eHealth intervention by women after gynaecological surgery results in a faster return to work, with a higher quality of life and less pain.

Cervical tourniquet in case of uncontrollable haemorrhage during caesarean section owing to a placenta accreta.

This case report describes a 38-year-old woman in whom a primary caesarean section for placenta previa was complicated by postpartum haemorrhage due to a placenta accreta. Despite tamponade with a Bakri balloon and placement of a B-Lynch suture, the amount of blood loss could not be effectively reduced. The blood loss was eventually minimised by the placement of a Penrose drain around the cervix as a cervical tourniquet. We think that a cervical tourniquet is an effective method of stopping haemorrhage during caesarean section, as shown in this case report, and we consider this technique to be a valuable addition to several existing methods through which fertility is preserved by preventing emergency hysterectomy.

Benzo[a]pyrene-induced transcriptomic responses in primary hepatocytes and in vivo liver: toxicokinetics is essential for in vivo-in vitro comparisons.

The traditional 2-year cancer bioassay needs replacement by more cost-effective and predictive tests. The use of toxicogenomics in an in vitro system may provide a more high-throughput method to investigate early alterations induced by carcinogens. Recently, the differential gene expression response in wild-type and cancer-prone Xpa (-/-) p53 (+/-) primary mouse hepatocytes after exposure to benzo[a]pyrene (B[a]P) revealed downregulation of cancer-related pathways in Xpa (-/-) p53 (+/-) hepatocytes only. Here, we investigated pathway regulation upon in vivo B[a]P exposure of wild-type and Xpa (-/-) p53 (+/-) mice. In vivo transcriptomics analysis revealed a limited gene expression response in mouse livers, but with a significant induction of DNA replication and apoptotic/anti-apoptotic cellular responses in Xpa (-/-) p53 (+/-) livers only. In order to be able to make a meaningful in vivo-in vitro comparison we estimated internal in vivo B[a]P concentrations using DNA adduct levels and physiologically based kinetic modeling. Based on these results, the in vitro concentration that corresponded best with the internal in vivo dose was chosen. Comparison of in vivo and in vitro data demonstrated similarities in transcriptomics response: xenobiotic metabolism, lipid metabolism and oxidative stress. However, we were unable to detect cancer-related pathways in either wild-type or Xpa (-/-) p53 (+/-) exposed livers, which were previously found to be induced by B[a]P in Xpa (-/-) p53 (+/-) primary hepatocytes. In conclusion, we showed parallels in gene expression responses between livers and primary hepatocytes upon exposure to equivalent concentrations of B[a]P. Furthermore, we recommend considering toxicokinetics when modeling a complex in vivo endpoint with in vitro models.

Perioperative outcomes using LigaSure compared with conventional bipolar instruments in laparoscopic hysterectomy: a randomised controlled trial.

OBJECTIVE: To compare the effects of LigaSure versus the conventional bipolar technique on operating time and blood loss during laparoscopic hysterectomy. DESIGN: A randomised controlled trial. SETTING: Three teaching hospitals. POPULATION: Women undergoing a laparoscopic hysterectomy for benign indications. METHODS: 140 women undergoing a laparoscopic hysterectomy were randomised for LigaSure or conventional bipolar instruments. MAIN OUTCOME MEASURES: Primary outcome was operating time from initial skin incision till detachment of the uterus. Secondary outcome measures were total operating time (from initial skin incision till final skin closure), time to dissect the adnexal ligaments, intra-operative blood loss and subjective evaluation by the surgeon of the instrument used. RESULTS: No differences in operating time (from initial skin incision till uterine detachment and initial skin incision till final skin closure) using LigaSure versus conventional bipolar instruments: 97.6 versus 91.8 minutes (P = 0.39, 95% CI - 7.6 to 19.2), and 148.1 versus 142.1 minutes (P = 0.46, 95% CI - 10.1 to 22.3), respectively. The mean blood loss using LigaSure versus conventional bipolar was 234.1 versus 273.1 ml (P = 0.46, 95% CI -39.1 to 52.7). Various subjective efficacy and instrument handling parameters were significantly different between the two instruments and between the different participating centres. CONCLUSIONS There were no significant differences in operating time and blood loss between the use of LigaSure and the use of conventional bipolar instruments during laparoscopic hysterectomy, even after correction for potential confounders. User satisfaction parameters were assessed as significantly different by surgeons of the participating centres.

How safe is the intravasation limit in hysteroscopic surgery?

BACKGROUND: Transcervical resection of myomas (TCR-M) is considered a safe hysteroscopic procedure if intravasation is limited. Complications may occur if gas formation during myoma resection leads to gaseous embolism. However, the incidence of emboli during transcervical myoma resection is unknown. Therefore in this study the occurrence of physiological changes that indicate the formation of emboli was retrospectively determined in patients undergoing hysteroscopic myoma resection. In addition, these changes were related to the amount of fluid intravasation. METHODS: The anesthesia records and operation files of 234 patients were screened for physiological changes that indicate embolism, as measured with standard intraoperative monitoring. These patients underwent surgery for intrauterine myomas with either a monopolar resectoscope with electrolyte-free distension fluid containing 3% sorbitol (limited to 1500-mL intravasation) or a bipolar resectoscope with normal saline solution (limited to 2500-mL intravasation). The patients were grouped according to the amount of fluid intravasation during the operation: Group 1: 500 mL or less, group 2: 500-1000 mL, group 3: 1000-1500 mL, and group 4: 1500-2500 mL. RESULTS: Physiological changes that could be attributed to gaseous embolism were observed in 33% to 43% of patients with 1000 to 2500 mL fluid intravasation during transcervical myoma resection. Nearly half of those patients had cardiovascular disturbances that indicated the formation of emboli. CONCLUSION: During transcervical resection of myomas, physiological changes that could be attributed to gaseous embolism frequently occurred. Therefore cardiovascular disturbances that indicate gaseous embolism during transcervical resection of myomas may occur despite the limitation of intravasation according to current view.

Malignant peritoneal mesothelioma in a 76-year-old woman with a history of asbestos fiber ingestion.

We report on a woman with malignant mesothelioma of the peritoneum. This is the first report of a subject with this disease who revealed a history of asbestos ingestion by asbestos-contaminated food. She presented with episodes of sweating and fever, ascites, and weight loss. At laparotomy, small tumor deposits were noted on the peritoneum. The omental cake was removed, together with the uterus, ovaries, and tubes which were all macroscopically normal. The diagnosis was established by immunohistochemistry and electron microscopy. Postoperatively, her complaints of fever and sweating disappeared. She refused further chemotherapy. After questioning her for asbestos exposure, she told us that, years ago, she used to prepare vegetables for cooking in rain water collected from a roof made of asbestos.

Ca2+, annexins, and GTP modulate exocytosis from maize root cap protoplasts

Protoplasts isolated from root cap cells of maize were shown to secrete fucose-rich polysaccharides and were used in a patch-clamp study to monitor changes in whole-cell capacitance. Ca2+ was required for exocytosis, which was measured as an increase in cell capacitance during intracellular dialysis with Ca2+ buffers via the patch pipette. Exocytosis was stimulated significantly by small increases above normal resting [Ca2+]. In the absence of Ca2+, protoplasts decreased in size. In situ hybridization showed significant expression of the maize annexin p35 in root cap cells, differ-entiating vascular tissue, and elongating cells. Dialysis of protoplasts with maize annexins stimulated exocytosis at physiological [Ca2+], and this could be blocked by dialysis with antibodies specific to maize annexins. Dialysis with milli-molar concentrations of GTP strongly inhibited exocytosis, causing protoplasts to decrease in size. GTPgammaS and GDPbetaS both caused only a slight inhibition of exocytosis at physiological Ca2+. Protoplasts were shown to internalize plasma membrane actively. The results are discussed in relation to the regulation of exocytosis in what is usually considered to be a constitutively secreting system; they provide direct evidence for a role of annexins in exocytosis in plant cells.

The effects of sex steroids on plasma levels of marker proteins of endothelial cell functioning.

We studied thirteen male-to-female (M-->F) and ten female-to-male (F-->M) transsexuals who, for four months, received cross-sex treatment with, respectively, ethinylestradiol and cyproterone acetate, and with testosterone esters. We assessed the effects of treatment on plasma levels of tissue-type plasminogen activator (tPA), von Willebrand factor (vWF), vWF-propeptide (vWF:AgII) and big-endothelin-1 (big-ET-1), four proteins that are markers of endothelial cell functioning. We also measured urokinase-type PA (uPA) and plasminogen activator inhibitor-type 1 (PAI-1), which may not be endothelium-derived but share major clearance pathways with tPA. In M-->F transsexuals, mean plasma levels of tPA (minus 4.4 ng/ml), big-ET-1 (minus 0.8 pg/ml), uPA (minus 0.5 ng/ml) and PAI-1 (minus 26 ng/ml) decreased (all Ps < or =0.02). The level of vWF increased (plus 24%; P = 0.005), while vWF: AgII did not change (P = 0.49). In F-->M transsexuals, levels of big-ET-1 increased (plus 0.4 pg/ml; P = 0.02), while tPA, uPA and PAI-1 did not change (all Ps >0.25). In this group vWF decreased (minus 14%; P = 0.06), but vWF:AgII did not change (P = 0.38). Estrogens and androgens have clear effects on plasma levels of endothelial marker proteins. The mechanisms behind these effects are complex and appear to involve both altered secretion (big-ET-1) and processing and/or clearance (vWF and possibly tPA). Therefore, effects of hormones on the levels of endothelial marker proteins do not necessarily reflect changes in endothelial cell functioning, at least with regard to changes in vWF level associated with the oral administration of high doses of ethinylestradiol and cyproterone acetate to healthy men and the parenteral administration of testosterone to healthy women.

Long-term follow-up of bone mineral density and bone metabolism in transsexuals treated with cross-sex hormones.

OBJECTIVE: It is unknown whether long term cross-sex hormone treatment affects the human skeleton. We monitored bone mineral density and biochemical markers of bone turnover for 28-63 months in 20 male-to-female transsexuals (M-->F) treated with anti-androgens and oestrogens, and 19 female-to-male transsexuals (F-->M) treated with androgens. They underwent gonadectomy 13-35 months after the start of cross-sex hormone administration. DESIGN: Bone mineral density (BMD) and the markers of bone turnover osteocalcin, alkaline phosphatase, fasting urinary calcium/creatinine and hydroxyproline/creatinine, were measured at baseline, after 1 year and after 28-63 months of cross-sex hormone administration. RESULTS: In oestrogen-treated M-->F, variables of bone turnover decreased significantly with consecutive measurements. BMD had increased significantly after 1 year, but decreased again to baseline levels after 28-63 months of cross-sex hormones. In F-->M, alkaline phosphatase levels increased during the first year. BMD did not change during the first year but had decreased significantly after 28-63 months following ovariectomy. In both M-->F and F-->M, the change of BMD correlated inversely with serum LH and FSH levels. Of all biochemical variables LH levels appeared to be the best predictor of loss of BMD; in the long-term LH levels were more elevated in testosterone-treated F-->M than in oestrogen-treated M-->F transsexuals. CONCLUSION: In M-->F, oestrogen treatment prevented bone loss after testosterone deprivation. In F-->M the testosterone dosage used, associated with a decline in serum oestradiol levels, was unable to maintain bone mass fully in all subjects in the longer term. The inverse relationship between BMD and serum LH levels suggests that the dose of hormone replacement has been too low in subjects with a decline in their BMD. Its cause might be underdosing or non-compliance in some patients. We propose that serum LH levels may be used as a measure of the adequacy of replacement with sex steroids.

Mortality and morbidity in transsexual subjects treated with cross-sex hormones.

OBJECTIVE: The optimum steroid hormone treatment regimes for transsexual subjects has not yet been established. We have investigated the mortality and morbidity figures in a large group of transsexual subjects receiving cross-sex hormone treatment. DESIGN: A retrospective, descriptive study in a university teaching hospital. SUBJECTS: Eight hundred and sixteen male-to-female (M-->F) and 293 female-to-male (F-->M) transsexuals. INTERVENTIONS: Subjects had been treated with cross-sex hormones for a total of 10,152 patient-years. OUTCOME MEASURES: Standardized mortality and incidence ratios were calculated from the general Dutch population (age- and gender-adjusted) and were also compared to side effects of cross-sex hormones in transsexuals reported in the literature. RESULTS: In both the M-->F and F-->M transsexuals, total mortality was not higher than in the general population and, largely, the observed mortality could not be related to hormone treatment. Venous thromboembolism was the major complication in M-->F transsexuals treated with oral oestrogens and anti-androgens, but fewer cases were observed since the introduction of transdermal oestradiol in the treatment of transsexuals over 40 years of age. No cases of breast carcinoma but one case of prostatic carcinoma were encountered in our population. No serious morbidity was observed which could be related to androgen treatment in the F-->M transsexuals. CONCLUSION: Mortality in male-to-female and female-to-male transsexuals is not increased during cross-sex hormone treatment. Transdermal oestradiol administration is recommended in male-to-female transsexuals, particularly in the population over 40 years in whom a high incidence of venous thromboembolism was observed with oral oestrogens. It seems that in view of the deep psychological needs of transsexuals to undergo sex reassignment, our treatment schedule of cross-sex hormone administration is acceptably safe.

Safety of cyproterone acetate: report of active surveillance.

Concern about a potentially increased risk of liver cancer associated to cyproterone acetate (CPA) treatment led to a postmarketing long-term surveillance study with historic accural of four groups of patients with sexual-hormonal disorders under treatment with CPA. The aim of the study was to provide a description of potential ADRs under CPA treatment with special emphasis on liver cancer. A long-term follow-up of 2506 patients was conducted. Six hundred and two persons were followed up retrospectively for longer than 10 years. In 16,721 patient-years of observation after the first CPA dose no malignant liver tumour was observed, whereas six would have been expected in this cohort. Seven incident, non-fatal benign liver tumours were found. Altogether 9.6% of a subset of 1685 patients with reported liver tests had, at some time, elevated liver enzymes. No cases were reported where CPA therapy had been discontinued due to severe liver disorder. We concluded from this active surveillance project, that CPA treatment is probably safe in the groups of patients followed up. Even though there was not a single case of liver cancer detected, the hypothesis of an elevated risk is being tested in an ongoing collaborative European case-control study which is examining the association of CPA use and primary hepatocellular cancer.

An epidemiological and demographic study of transsexuals in The Netherlands.

This is an epidemiological and demographic study of 1285 transsexuals in the Netherlands. The data were collected from 1975 to the end of 1992. Over 95% of the Dutch transsexuals have been treated at the study center. Between 1975 and 1984 the annual number of female-to-male transsexuals increased, stabilizing thereafter. In the male-to-female transsexuals this trend continued up to 1989, declining slightly thereafter. Over the last 5 years on average 50 (range 38-60) male-to-female transsexuals and 21 (range 14-25) female-to-male transsexuals received surgical and/or hormonal treatment yearly. The sex ratio remained stable over this period: 3 male vs. 1 female subject. The calculated prevalence of transsexualism in The Netherlands is 1:11,900 males and 1:30,400 females. Transsexuals live predominantly in urbanized areas, but those living in nonurbanized areas show an even distribution over the country. The majority of female-to-male transsexuals apply for reassignment between the ages of 20-25, seldom in middle ages. The majority of male-to-female transsexuals do so between the ages of 25-30 and middle-aged subjects are not rare. Between 77-80% of both categories receive surgical and/or hormonal treatment. Five male-to-female transsexuals regretted sex reassignment.

The effect of androgen treatment on bone metabolism in female-to-male transsexuals.

Histomorphometry was performed in iliac crest biopsies from 15 female-to-male (F-M) transsexuals with a mean age of 30 +/- 6.1 (SD) years. At the time of study, they had been treated with parenteral testosterone esters (250 mg/2 weeks) or oral testosterone undecanoate (160 mg/day). The median androgen treatment duration was 39 months. The patients had undergone hysterectomy and bilateral ovariectomy. The bone biopsy was obtained after double tetracycline labeling. Histomorphometric results were compared with data from 8 postmenopausal women and with data from 11 healthy men who had died suddenly. Dynamic parameters were compared with data from the literature. The biochemical picture was characterized by serum testosterone concentrations lower than in eugonadal men and estradiol concentrations lower than in eugonadal women and elevated gonadotrophin levels. The bone mineral density in the F-M transsexuals was as expected for age (Z-score -0.31 +/- 1.49). Cortical thickness was significantly higher in F-M transsexuals than in both control groups. Trabecular bone structure was similar in F-M transsexuals and both control groups. The bone formation parameters were generally lower in F-M transsexuals than in the control groups. The eroded surface was lower in F-M transsexuals than in postmenopausal women. The low bone turnover and preservation of trabecular bone is consistent with the assumption that testosterone treatment protects the bone in these F-M transsexuals from the deleterious effects of estrogen deficiency. The increased cortical thickness suggests an anabolic effect of the testosterone treatment.

Effects of estrogens only on the prostates of aging men.

PURPOSE: The effects of estrogen only on prostate tissue were studied in 9 aging male transsexuals who had undergone orchiectomy. MATERIALS AND METHODS: Prostate volume was measured by ultrasound. Biopsies were stained for prostatic acid phosphatase (PAP), prostate specific antigen (PSA), Ki-67 and sex steroid receptors. RESULTS: Prostates were small, and biopsies showed PAP and PSA in most cases. No malignancy was found. Few androgen receptors were detectable but there were ample estrogen and progesterone receptors in stroma and epithelium. CONCLUSIONS: Prostates were small after long-term estrogens only. The sex steroid receptor content was considerably changed. PSA and PAP in the specimens suggested that their production does not depend on testicular androgens alone.

The effect of one-year cross-sex hormonal treatment on bone metabolism and serum insulin-like growth factor-1 in transsexuals.

The effects of treatment with estrogens and antiandrogens in male to female (M-->F) transsexuals and androgens in female to male (F-->M) transsexuals on their respective bone metabolism, bone mineral density (BMD), serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels were investigated. BMD and variables of bone turnover in serum were measured at baseline and after 3 months (except for BMD) and 1 yr of treatment in 56 M-->F and 35 F-->M transsexuals. Serum IGF-I, IGFBP-3, and propeptide of type I procollagen (P1CP) were measured at baseline and after 1 yr of treatment in 10 M-->F and 10 F-->M transsexuals. In M-->F, BMD increased significantly. Bone turnover decreased, as shown by a significant decline in levels of osteocalcin, alkaline phosphatase, P1CP, and fasting urinary calcium/creatinine and hydroxyproline/creatinine ratios. Serum IGF-I levels decreased significantly without significant changes in IGFBP-3 levels. In F-->M, BMD did not change. Bone formation increased, as suggested by an increase in alkaline phosphatase and a borderline increase in P1CP values. IGF-I levels increased significantly, whereas no significant changes were seen in IGFBP-3 levels. We conclude that in males, estrogens (in combination with antiandrogens) decrease bone turnover, with a subsequent increase in BMD and a decrease in serum IGF-I. In females, testosterone administration increases bone formation, but this is not reflected in an increased BMD, whereas serum IGF-I increases.