Ondansetron versus dexamethasone. SIR,-Dr Jones and colleagues (Aug 24, p 483) compare ondansetron with dexamethasone for prevention of chemotherapy ...
surgery in our department. The 2 patients, aged 26, came from an ultraorthodox Jewish family of Yemenite origin. At an early age they were aware of a powerful desire to be female and they strongly identified with their four sisters. From the age of 16 they dressed like girls and prayed to be turned into women. At the time of psychological evaluation at 23 years of age they had been receiving hormone therapy regularly, underwent depilation, and looked like women. They had normal lifestyles, working as elementary school teachers and dating men regularly, with whom they did not have sexual relations on religious grounds. They proved to have normal intelligence scores with a proper perception of reality and a functional rigidity about sexual orientation. Close and prolonged symbiosis between the twins was revealed. A sexual reassignment operation led to good functional and cosmetic results in both, with successful social adaptation and physical wellbeing being attained. The fact that transsexualism occurs in most, if not all, ethnic groups despite wide cultural diversity may imply a biological basis for this disturbance. This is further supported by the observation that psychotherapeutic or behaviour treatment rarely succeeds, whereas satisfaction with the extreme measure of surgery is usually high, with acceptable psychosocial adjustment.4 An effect of androgens to masculinise both genitalia and brain in fetal life has been suggested, and our report seems to be consistent with such an intrauterine effect. However, it is clear that a common genetic or postnatal psychosocial origin cannot be excluded. Nevertheless, further study of monozygotic twins discordant for sexual orientation,5 as well as of gender dysphoria in dizygotic same-sex twins, as you suggest, may provide more information on the origin of this disorder of obscure aetiology. Departments of Plastic Surgery and Obstetrics and Gynaecology, Sheba Medical Centre, Tel-Hashomer 52621, Israel
HAGAI TSUR AMIRAM BORENSTEIN DANIEL S. SEIDMAN
Vay S. A difference in hypothalamic structure between heterosexual and homosexual men. Science 1991; 253: 1034-37 2. Swaab DF, Roozendaal B, Ravid R, Velis DN, Gooren L, Williams RS. Suprachiasmatic nucleus m aging: Alzheimer’s disease, transsexuality and Prader-Willi syndrome. Progr Brain Res 1987, 72: 301-10. 3. Swaab DF, Hofman MA. An enlarged suprachiasmatic nucleus in homosexual man. Brain Res 1990; 537: 141-48. 4. Blanchard R, Steiner BW, Clemmesen LH. Gender dysphoria, gender reorientation, and the clinical management of transsexualism. J Consult Clin Psychol 1985; 53: 295-304. 5. Suddath RL, Christison GW, Torrey EF, Casanova MF, Weinberger DR. Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. N Engl J Med 1990; 322: 789-94.
SIR,-Dr Jones and colleagues (Aug 24, p 483) compare ondansetron with dexamethasone for prevention of chemotherapyinduced emesis. Dexamethasone was first reported to be antiemetic in 1981; however, its role has primarily been as an adjunct to other regimens.1 Five controlled trials have included a dexamethasone alone arm. 1-5 A comparison of the pooled efficacy of dexamethasone in these trials with the efficacy noted by Jones et al suggests that results were superior in Jones’ trial:
CR =complete response, PR
= part!a! response al an interaction between treatment and course Jones report number on day 1 of their crossover trial, and the analysis for day 1 is done on treatment period 1 only. However, table 11 is a combination of the results of both periods and does not subdivide according to period. Also, the exclusion of 9 patients who required rescue therapy on day 1 from the analysis for days 2-5 causes differential drop-outs and biases the results. Note, these excluded patients were failures on dexamethasone and non-failures on ondansetron. The et
efficacy of both agents on day 1 was similar (83% ondansetron, 79% dexamethasone): however, 3% were therapeutic failures in the ondansetron group and 17% in the dexamethasone group, which suggests a different conclusion from Jones and colleagues’. School of
Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599. USA
WILLIAM D. FIGG
Aapro MS, Alberts DS. Dexamethasone as an antiemetic m patients treated with cisplatin. N Engl J Med 1981, 305: 520 2. Markman M, Sheidler V, Ettinger DS, et al. Anti-emetic study of dexamethasone: randomized, double-blind, crossover study with prochlorperazine in patients receiving cancer chemotherapy N Engl J Med 1984; 311: 549-52. 3. Ibrahim EM, Al-Idrissi HY, Ibrahim A, et al. Antiemetic efficacy of high-dose dexamethasone: randomized, double-blind, crossover study with high-dose metoclopramide in patients receiving cancer chemotherapy. Eur J Cancer Clin Oncol 1986; 22: 283-88. 4. Aapro MS, Plezia PM, Alberts DS, et al Double-blind crossover study of the antiemetic efficacy of high-dose dexamethasone versus high-dose metoclopramide. J Clin Oncol 1984; 2: 466-71. 5. Sumer T, Abu-Melha A, Maqbool G, et al. Dexamethasone as an antiemetic in children receiving cis-platinum. Am JPediatr Hematol Oncol 1988; 10: 126-28. 6. Kns MG, Gralla RJ, Tyson LB, et al Controlling delayed vomiting: double-blind, randomized, trial comparing placebo, dexamethasone alone, and metoclopramide plus dexamethasone in patients receiving cisplatin J Clin Oncol 1989; 7: 108-14. 1
Pneumocystis carinii pneumonia and high-dose dexamethasone to prevent emesis of chemotherapy SIR,-We would like to add a follow-up comment and note of to our paper (Aug 24, p 487) and that of Dr Jones and colleagues (p 483) concerning the use of dexamethasone (alone or with ondansetron) as antiemetic prophylaxis for cancer caution
chemotherapy. In both trials few steroid-related side-effects were reported. However, in a separate group of patients treated during the same period at this hospital two episodes of life-threatening Pneumocystis carinii pneumonia (PCP) like infection have been recorded. A 41-year-old woman presented in choriocarcinoma. She was put on weekly
October, 1990, with alternating EMA/CO chemotherapy (etoposide, methotrexate, actinomycin-D/ cyclophosphamide, vincristine), initially with dexamethasone 8 mg thrice daily for 2 days as antiemetic prophylaxis. Ondansetron was added when dexamethasone alone failed to control her emesis. After 8 weeks of therapy she was admitted to hospital with a short history of fever, dry cough, and breathlessness. She was hypoxic (p02 on air 7’8kPa and her chest X-ray showed appearances consistent with PCP. She was transferred to intensive care where her ventilation was assisted with continuous positive airway pressure (CPAP). She was given high-dose co-trimoxazole, acyclovir, fluconazole, and erythromycin. No causative organism was isolated but over the next 14 days she made an excellent recovery. She was able to complete her chemotherapy with ondansetron alone as antiemetic prophylaxis and she remains well and in remission. A 26-year-old woman who also had choriocarcinoma was put on EMA/CO March 9, 1991, with antiemetic prophylaxis similar to that of the first patient. After 10 weeks of therapy she was admitted with pyrexia, dry cough, and breathlessness. She was also hypoxic (p0;, on air 72 kPa) and her chest X-ray was consistent with PCP. P carinii cysts were observed in samples obtained by sputum induction and she was treated with high-dose co-trimoxazole plus ventilatory support with CPAP. She also made a full recovery and has now completed her chemotherapy and remains in remission. Both patients received pentamidine inhalations weekly during the remainder of their chemotherapy. These 2 patients demonstrated a complication that we had not previously encountered. EMA/CO has been used in this unit since 19791 and in ten years to 1989, 148 patients were treated with no episodes similar to the 2 described. Over that time dexamethasone was frequently used as part of the antiemetic prophylaxis but normally in total doses of 8-12 mg per cycle of chemotherapy. In the past two years since our antiemetic policy changed a further 39 patients have been treated, including the 2 cases described above. During this time dexamethasone has been given at a dose of 8 mg thrice daily for 2 days (total dose 48 mg). This higher dose was used