endometriosis and clomiphene citrate
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antigen in serum before treatment, and 4 of these had AIDS. 5 of 11 Iin the placebo group were antigen positive, and 3 had AIDS. 5(42%) of the 12 in the amoxycillin group completed 3 weeks oftreatment compared with 9 (82%) of 11 controls. This suggests thatamoxycillin was poorly tolerated. However, 4 patients (2 from eachgroup) stopped treatment prematurely for symptoms subsequentlyattributed to another condition, such as Pneumocystis carinii
. pneumonia (PCP). A further 2 patients declined to have more than 2weeks of amoxycillin because they disliked the taste. 3 patients onamoxycillin had true adverse reactions. 2 began treatment afterrecovering from an episode of PCP: in 1 fever and rash after onedose was interpreted as penicillin allergy, and the other hadpruritus, without a rash, 16 days after treatment started. The thirdpatient, with prior oral candidiasis, had a symmetrical macular rashafter 14 days, which resolved within a week of stopping treatment.There was concurrent serological evidence of infection with
Toxoplasma gondii, with detectable IgM and a dye test positive at4000 U before treatment but undetectable IgM and a dye test of1000 U 3 weeks later. Investigations for cerebral toxoplasmosis werenegative.A further 9 patients (5 with CDC group 2 or 3 disease, 4 with
group 4 disease) were prescribed amoxycillin/probenecid for
syphilis during 1988-89, after full discussion of the treatmentoptions and the importance of strict compliance. In contrast to thosein the trial, only 1 patient, who had headaches, did not complete thetreatment. 1 patient reported a generalised erythematous rash after11 days. It resolved while he continued taking the medication. Atthat time a ’Monospot’ test was reactive and the blood film showedatypical lymphocytes consistent with infectious mononucleosis. Arepeat monospot test was negative 3 weeks later.Thus, in total, only 2 of 20 patients had maculopapular rashes
similar to those described by Battegay et al. In the patient withevidence of concurrent infectious mononucleosis, amoxycillin wascontinued without ill-effect. In the other case there was evidence of
toxoplasmosis, which, though causing a glandular fever type illness,is not usually associated with aminopenicillin-induced rash. Apartfrom the 1 patient with a genuine penicillin allergy no potentiallyserious adverse events occurred. Oral nystatin prevented oralcandidiasis in all the patients treated. Few gastrointestinalsymptoms were reported: 3 patients complained of nausea butcontinued with the medication and only 2 patients (both in the trial)reported transient diarrhoea, passing three or four stools per day for4 days. We suggest that amoxycillin/probenecid does not oftenproduce serious adverse reactions in patients with group 4 HIVinfection, and the development of a rash, pruritus, or headache neednot lead to curtailment of treatment if the symptoms can be relieved
by other means.
Division of Sexually Transmitted Diseases,Clinical Research Centre,Harrow. Middlesex
P. E. HAYD. TAYLOR-ROBINSON
Department of Genitourinary Medicine,St Mary’s Hospital,London W2 1NY, UK
S. WALDROND. GOLDMEIER
1. Hook EW III. Syphilis and HIV infection. J Infect Dis 1989; 160: 530-34.2. Dunlop EMC. Survival of treponemes after treatment: comments, clinical conclusions
and recommendations. Genitourin Med 1985; 61: 293-301.3. Morrison RE, Harrison SM, Tramont EC. Oral amoxycillin, an alternative treatment
for neurosyphilis. Genitourin Med 1985; 61: 359-62.4. Komhauser DM, Petty BG, Craig W, et al. Probenecid and zidovudine metabolism.
Lancet 1989; ii: 473-75.
Endometriosis and clomiphene citrateSIR,-Altered progesterone metabolism and luteal function havebeen reported in infertile women with endometriosis,1,2 similarfindings being reported in women receiving clomiphene.3,4 Thesereports stimulated the following study of a possible causal relationbetween endometriosis and clomiphene.A retrospective analysis was done on 37 couples who had been
infertile for an average of 23 months, the woman having evidence ofanovulation or impaired ovulation. Laparoscopy confirmed normalpelvic findings and tubal patency. The control group of 42 coupleshad been infertile for an average of 19 months but the woman had
confirmed ovulation and normal laparoscopic fmdings. Impairedsemen quality was the predominant cause of infertility in thecontrols. The women in the study group were given clomiphenecitrate 250-750 mg per cycle. The mean duration of treatment was13 months, ovulation being confirmed via mid-luteal-phase plasmaprogesterone levels. After treatment laparoscopy was repeated. Inthe control group, where therapy was directed towards the malepartner, laparoscopy was repeated 18 months after the initialassessment.
The frequency of endometriosis on follow-up laparoscopy was57% in the study group (American Fertility Society 1985classification grade 1 in 14, grade 2 in 6, and grade 3 in 1) and 7% (allgrade 1) in the controls (p < 0-05, X2 test).Women on clomiphene therapy achieve presumptive ovulation
rates of 70-90% but pregnancy rates of only 30-44%.5,6 Thisdiscrepancy has been attributed to the antagonist oestrogenicactivity of clomiphene, resulting in a decreased ability to transportor sustain the ovum, spermatozoa, or early embryo at the ovarian,tubal, endometrial, or cervical mucus levels? In part this
explanation is supported by the fact that 5 women in the studygroup had impaired cervical mucus on post-clomiphene spermmigration testing; these 5 women did not develop endometriosis.More significant is the development of pelvic endometriosis in 57%of women in the clomiphene group. This could be one explanationfor continued infertility in these women. Women on long-termclomiphene citrate should have a follow-up laparoscopy to excludethe development of endometriosis-and this recommendation maybe relevant to other ovulation induction regimens.124 Sturt Street,Adelaide, South Australia 5000 JOHN M. SVIGOS
1. Schmidt CL. Endometriosis: a reappraisal of pathogens and treatment. Fertil Steril1985; 44: 157.
2. Cheesman KL, Cheesman SD, Chatterton RT, Cohen MR. Alterations in
progesterone metabolism and luteal function in infertile women with
endometriosis. Fertil Steril 1983; 40: 590.3. Cook CL, Schroeder JA, Yussman MA, Sanfilippo JS. Induction of luteal phase
defect with clomiphene citrate. Am J Obstet Gynecol 1984; 149: 613.4. Dlugi AM, Laufer N, Botero-Ruiz W, et al. Altered follicular development in
clomiphene citrate versus human menopausal gonadotrophin-stimulated cycles forin vitro fertilization. Fertil Steril 1985; 43: 40.
5. Adashi EY, Rock JA, Sapp KC, Martin EJ, Wentz AC, Jones GS. Gestationaloutcome of clomiphene related conceptions. Fertil Steril 1979; 31: 620.
6. Wu CH. A rational and practical approach to clomiphene citrate. Clin Obstet Gynecol1984; 27: 953.
7. Scialli AR. The reproductive toxicity of ovulation induction. Fertil Steril 1986; 45:315.
Ginkgo biloba extractsSiR,—Your Round the World correspondent (Dec 23/30, p 1513),writing about Ginkgo biloba extract (EGb 761) products ’Tebonin’and rokan, makes many false assertions and falls far short of normalLancet standards of critical, but fair, reporting.The first paragraph is highly misleading. It scurrilously
insinuates that there are no substantial data behind EGb and thatthe German product licences were granted on the basis of almostanecdotal reports from a handful of eccentric physicians. In fact thestandardised extract EGb 761, developed by Dr Willmar SchwabeGmbH, is a thoroughly researched phytopharmaceutical productwith hundreds of pharmacological and clinical investigations on theextract and specific constituents. Clinical studies include fortydouble-blind trials, and independent analysis and meta-analysis ofthese by university biometrics departments in Berlin and Hannoveryielded clear positive verdicts on the efficacy of EGb 761 in bothperipheral vascular disease and cerebral insufficiency.EGb 761 has been licensed not only in Germany, after the
submission of full pharmacological, toxicological, and clinical
documentation, but also in many other European countries andoverseas.
The negative "scientific evaluation" your correspondent refers tohas been criticised as being selective and incorrect and thus unsuitedfor inclusion in any objective assessment of EGb. Poorly designedstudies were included in the evaluation if their results wereinconclusive whereas other well-designed studies with thoroughstatistical analysis were omitted altogether or only partly included or