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The relationship of gonadal activity and chemotherapy-induced gonadal damage.

We tested the hypothesis that chemotherapy-induced gonadal damage is proportional to the degree of gonadal activity during treatment. Thirty studies that evaluated gonadal function after cyclophosphamide therapy for renal disease or combination chemotherapy for Hodgkin's disease or acute lymphocytic leukemia provided data for analysis. Data were stratified according to sex, illness, chemotherapeutic regimen and dose, and pubertal stage at the time of treatment. Chemotherapy-induced damage was more likely to occur in patients who were treated when sexually mature compared with those who were treated when prepubertal. Males were significantly more frequently affected than females when treated for renal disease or Hodgkin's disease. Chemotherapy-induced damage was also more likely to occur when patients were treated with large doses of alkylating agents. These data suggest that chemotherapy-induced damage is proportional to gonadal activity. Further efforts are needed to test whether induced gonadal quiescence during chemotherapy will reduce the strikingly high incidence of gonadal failure following chemotherapy.

Adolescent↗

Gestodene. A review of its pharmacology, efficacy and tolerability in combined contraceptive preparations.

The newer progestogens gestodene, desogestrel and norgestimate were developed in an attempt to produce agents with more selective progestational activity that would improve cycle control and minimise metabolic changes and adverse events while effectively preventing pregnancy. In clinical practice, gestodene is combined with ethinylestradiol in monophasic or triphasic combined oral contraceptive preparations. The drug has pharmacokinetic advantages over the other new progestogens in that it is active per se (the others are prodrugs) and has high bioavailability (approximately 100%). The ability of gestodene-containing oral contraceptives to inhibit ovulation is similar to that of preparations containing other progestogens although the required dosage is lower. In common with oral contraceptives containing desogestrel or norgestimate, and in contrast with those containing levonorgestrel, gestodene-containing preparations are associated with neutral or positive changes in lipid and carbohydrate metabolism. The effects of gestodene preparations on coagulation parameters, like those of desogestrel and levonorgestrel, are balanced by changes in the fibrinolytic system. Although the impact of these changes on clinical cardiovascular end-points has not been determined, the altered lipid profile is not likely to have significant clinical relevance because of the predominantly thrombogenic nature of cardiovascular disease in oral contraceptive users. Pregnancy rates and Pearl Indices with gestodene-containing preparations are low and similar to those with preparations containing other progestogens. Most pregnancies are attributable to user failure. Cycle control appears to be better with gestodene preparations than with levonorgestrel preparations, and available data suggest that cycle control may also be better with monophasic gestodene/ethinylestradiol than with monophasic desogestrel- or norgestimate-containing preparations, and better with triphasic gestodene- than with triphasic levonorgestrel- or norgestimate-containing preparations. However, differences between the new progestogen-containing preparations need to be confirmed in further large-scale trials. The most common adverse events with gestodene/ethinylestradiol are headaches and breast tension; the incidence of short term adverse events, including acne, is similar to that with preparations containing other progestogens. Changes in blood pressure and bodyweight are negligible. There are no comparative data on the incidence of cardiovascular events with gestodene-containing and other combined preparations. While the risk of breast cancer appears to be increased with long term combined oral contraceptive use in certain patient subgroups, this risk needs to be balanced against the noncontraceptive benefits of these preparations.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

Determinants of contraceptive switching behavior in rural Sri Lanka.

This study examines the influence of a selected set of determinants of contraceptive method switching in rural Sri Lanka. Of interest is the question of how change in contraceptive practice at the individual level can account for patterns observed at the aggregate level. Based on calendar data on contraceptive use over a 3-year period, collected for more than 3,000 married women in a 1986 survey, the multivariate analysis shows that women who attain all or a significant proportion of their desired fertility tend to switch to more effective methods. Women who experience method failure tend to switch methods, usually to a type that is more effective. The woman's background determinants of age and education have small but significant effects on method switching, whereas the effect of household economic well-being is not significant. There is strong indication that rural couples are practicing contraception in a nonrandom fashion, switching methods in accordance with changes in their fertility motivations and contraceptive experience.

Choice Behavior↗

Implantable contraceptives for women: effectiveness, discontinuation rates, return of fertility, and outcome of pregnancies.

Progestogen-only contraceptive implants are highly effective. In most studies, 5-year cumulative pregnancy rates are less than 1.5/100 women for Norplant and Norplant II. No study has yet reported any failures with Implanon. Weight over 70 kg and age at insertion under 25 years both increase the failure rate of Norplant and Norplant II; however, data are as yet lacking for Implanon. The effectiveness of other progestogen-only implants for which there are as yet few data are unlikely to be any different. Continuation rates are high compared with other hormonal methods and with the intrauterine device. In most cohorts at least 35% of women, and often many more, are still using Norplant by the end of 5 years. Rates vary according to a number of factors, including population studied, age, and parity. Menstrual disturbance is by far the most common reason for discontinuation, with headache, acne, weight gain, and desire for pregnancy accounting for other common reasons for implant removal. Fertility returns rapidly following implant removal, and pregnancy rates (76-100% 1 year after removal) are usually no different from those following discontinuation of any other contraceptive method. There is no increase in the risk of ectopic pregnancy, fetal malformation, or impaired infant health in pregnancies conceived either during implant use or after removal.

Age Factors↗

Donation of oocytes as treatment for infertility in patients with premature ovarian failure. Awarded the "Nicolau de Moraes Barros" prize for gynecology.

A total of 7 cycles of embryo transfer by oocyte donation were performed on 5 patients with premature ovary failure (POF). All donors were under 35 of age and the recipients average age was 38.6 years. For synchronization between donor and recipient a semi programmed menstrual cycle was used by means of oral contraceptive followed by ovarian stimulation of donor with clomiphene citrate and human menopausal gonadotrophin. The recipients were easily adjusted to the donors by a flexible model of gradually increasing doses of estradiol valerianate. The average number of oocytes donated was 3.14 and average embryo cleavage rate was 80.2%. The average number of embryos transferred was 2.57. Embryo implantation rate was 22.2%. Clinical gestations occurred in 57.1% of the cycles. This series is probably the first one in Brazilian literature on oocyte donation as treatment for infertility in patients with premature ovarian failure.

Adult↗

Comparison of a paper pill with a conventional oral contraceptive tablet.

A multicentre clinical trial comparing a novel formulation (the Paper Pill) of a combined oral contraceptive containing 30 microgram ethinyloestradiol and 150 microgram levonorgestrel with a conventional tablet formulation (Microgynon 30) has been carried out in 336 women over 6 cycles. There were no pill failures in women taking either preparation with one exception in the Microgynon 30 group which was due to poor patient compliance. Cycle control judged by cycle length, duration and amount of withdrawal bleeding and the incidence of intermenstrual bleeding was good in both groups. The number of adverse effects was slightly less in the Paper Pill group and fewer withdrawals for questionnaire reasons were noted than in the Microgynon 30 group. A questionnaire showed that the Paper Pill was accepted well by the majority of women in the trial.

Administration, Oral↗

The efficacy and tolerability of Valette: a postmarketing surveillance study.

OBJECTIVES AND METHODS: A postmarketing survey was carried out to determine the efficacy and tolerability of Valette (dienogest 2.0 mg and ethinylestradiol 0.03 mg) in routine gynecological practice. RESULTS: Valette had excellent contraceptive efficacy (unadjusted Pearl index 0.14), with 11 unplanned pregnancies from a total of 92 146 cycles of exposure, of which at least four were attributable to user failure. Cycle control was good, with spotting and breakthrough bleeding, which affected 5.0% and 3.4% of women, respectively, during the first cycle, becoming less frequent thereafter. Silent menstruation, i.e. the absence of withdrawal bleeding, affected on average 2.0% of women per cycle and 5.9% within the observation period. Valette was well tolerated. The most common adverse drug reactions were mastalgia (1.46% of all users), weight gain (1.11%), headache (0.98%), nausea/vomiting (0.96%), dysmenorrhea (0.35%), decreased libido (0.31%) and depressive moods (0.28%). The dropout rate due to adverse drug reactions was only 3.2%. Only six of the 16 267 women reported events which were considered to be serious adverse drug reactions; all recovered with appropriate treatment. CONCLUSIONS: These results confirm those from previous clinical trials, and demonstrate that Valette is highly effective, very well tolerated and produces excellent cycle control in routine practice.

Adolescent↗

Natural family planning effectiveness in Belgium.

The aim of the study was to check, in a European environment, the practical efficiency and the acceptability of a recent natural family planning (NFP) method. This method includes a double check to detect the beginning as well as the end of the fertile phase of the menstrual cycle. Up to now, 71 women of reproductive age have been registered. They agreed to provide their symptothermal charts and related information. Average age is 32 years. Average fertility is 2 children/woman. Fifty-nine percent of the participants have a professional occupation. The same percentages are found in those accepting a contraceptive method (oral contraceptives or intrauterine devices). Until today 1240 cycles (103 women-years) of experience have been gathered. The average participation was 17.5 cycles/woman. No method failure has been reported. One unintended pregnancy due to unprotected sexual intercourse during the fertile phase occurred (user failure). Overall Pearl Index (PI) was 0.96. In 84% of the cycles, no protected intercourse was reported (NFP only). According to PI, practical efficiency of the NFP method analyzed was 1.31. Sexual abstinence during the fertile phase was found in 71.4% of the cycles.

Adolescent↗

Quinacrine non-surgical female sterilization in Bangladesh.

This study was undertaken to evaluate the efficacy, safety, and acceptability of transcervical applications of quinacrine along with other adjuvants, such as ampicillin and ibuprofen, for sterilization. The cohort consisted of 750 normal women who requested sterilization and volunteered for this method at the family planning clinic of a tertiary hospital and community clinics in Chittagong, Bangladesh. Several different protocols were followed from October 1989 to April 1999. Each woman received one or two insertions of 180 mg or 252 mg quinacrine with or without adjuvants including 55.5 mg ibuprofen or 125 mg ampicillin. Supplementary contraception was given in the form of combined oral contraceptive pills, barrier methods, or injection of depot medroxyprogesterone acetate for 3 months. Details of each protocol are described in the text. The gross pregnancy failure rate for insertion of 180 mg in 590 women was 3.9% compared to 1.9% for the 160 who received 252 mg. There were no serious complications, and side effects were transient. We conclude that quinacrine non-surgical sterilization is a safe, acceptably effective method when two insertions of 252 mg quinacrine with medroxyprogesterone injection as a supplement is used.

Adult↗

A study of candidosis: the role of fomites.

This study investigates treatment failure and recurrences of vulvo-vaginal candidosis. It reviews the factors possibly associated with both. Patients attending a department of genitourinary medicine with recurrent candidosis (N = 186) were entered in the trial. The patients were investigated for evidence of candidosis from vagina, rectal wall and buccal mucosa and were given antifungal therapy. Prevention and reinfection via fomites was studied by means of a single blind parallel study comparing the effect of soaking undergarments in the amphoteric biocide Tego 103G with the effect of a placebo soak. General and possible contributory factors influencing treatment and failure and recurrences were considered. The success rate of miconazole therapy was typical of any imidazole therapy: 85.4%. There was no evidence that modern oral contraceptives played a role in candidosis. Oral nystan reduced the rectal wall carriage from 39.2% to 23.2%. Oral yeast carriage rate in women was 37.6%. The recurrence rate over a six month period was 47.4%. The laboratory results of Tego soaking reduced the yeast carriage on panties from 85.2% to 23.4%. However, no evidence was found in the trial results that panties were a significant source of reinfection.

Antifungal Agents↗

A kidney biopsy is clearly mandatory to confirm the indication of plasma exchanges in adult haemolytic uraemic syndrome.

In case of haemolytic uraemic syndrome, it is not always possible to identify on a pure clinical basis the different kidney lesions responsible for the syndrome. We report a series of six cases without thrombotic microangiopathy, which emphasizes the need to perform a kidney biopsy as early as possible, so as to confirm the actual usefulness of plasma exchanges (PE) commonly carried out in emergency in every case of adult haemolytic uraemic syndrome. PATIENTS AND METHODS--Files of patients who were treated for haemolytic uraemic syndrome over the past 14 years were reviewed. Patients in whom thrombotic microangiopathy had been excluded by renal histology data were studied. Every patient was promptly treated with hypotensive drugs, so as to obtain blood pressure levels not exceeding 160-90 mmHg. Dialysis was performed in two patients. Daily PE with fresh frozen plasma were carried out in three patients as early as the first 24 hours after admission, and discontinued immediately after thrombotic microangiopathy could be excluded. RESULTS--All the patients met the usual criteria for diagnosis of haemolytic uraemic syndrome. Elevated liver enzymes were also found in the four cases of preeclampsia, consisting with diagnosis of severe HELLP syndrome. One case was associated with oestrogen therapy. Glomerular lesions were seen in four patients: slight endotheliosis in three cases of preeclampsia; marked lesions of IgA mesangial deposits in the patient who had been treated by contraceptive pill. Three patients had acute tubular necrosis and three had intense lesions of nephrosclerosis. Complete remission was obtained in every case of preeclampsia. Renal failure persisted in two cases (IgA glomerulopathy and one case of nephrosclerosis). DISCUSSION--The histological heterogeneity of haemolytic uraemic syndrome has been already well demonstrated. Typical lesions of thrombotic microangiopathy are usually classified into predominant glomerular lesions, pure arteriolar and mixed lesions. In other cases, thrombotic microangiopathy is not found: kidney lesions may be glomerular (endotheliosis, various subtypes of glomerulonephritis), tubular (acute tubular necrosis) or vascular (nephroangiosclerosis). In every aetiological circumstance, several different lesions may be found together. The usefulness of PE has been proved in thrombotic thrombocytopenic purpura, has been suggested in haemolytic uraemic syndrome and to a lesser extent in persistently severe HELLP syndrome. Unfortunately, none of these reports gave any information about kidney lesions responsible of acute renal failure. CONCLUSION--The haemolytic uraemic syndrome is a syndrome: thrombotic microangiopathy has to be proven when treatment by PE is planned, except in some severe clinical circumstances.

Adult↗

Poland's syndrome and premature ovarian failure.

A 19-year-old female with Poland's Syndrome with associated left amastia, scoliosis, and left Sprengel deformity developed secondary amenorrhea from premature ovarian failure. Her menarche was at 13 years of age, and periods were regular and monthly until 15 years of age when her periods suddenly stopped. Her hormonal evaluation was significant for elevated FSH (46.5 mIU/ml) and LH (28.5 mIU/ml), and low estradiol (23 pg/ml). Anti-ovarian antibody level was less than 2 units (normal < 4 units). Her chromosomes were 46XX, by both standard karyotype and by fluorescence in situ hybridization. On transabdominal and transvaginal ultrasonography, ovaries were not visualized, the uterus was of normal size and anteverted and both kidneys were normal. The patient began hormone replacement therapy with conjugated estrogen (Premarin) 0.625 mg po daily and progestin (Provera) 5 mg on days 20 to 25. Because of menopausal symptoms, she was switched to a combination oral contraceptive (OC) with 20 mcg ethinyl estradiol that was eventually increased to 30 mcg. Her menopausal symptoms (hot flashes and sweating) improved on the continuous 30 mcg ethinyl estradiol combination OC. Following a comprehensive review of the literature, this is the first reported case of Poland's Syndrome associated with premature ovarian failure; however, this association may be coincidental.

Adult↗

Problems in management of the pregnant patient with rheumatic heart disease and valve prosthesis.

The clinical course, through pregnancy and delivery, of a 30-year-old woman with rheumatic heart disease and a prosthetic mitral valve is presented. Despite maternal development of congestive cardiac failure and atrial fibrillation, the delivery of a healthy infant was achieved. The problems encountered during pregnancy and delivery in patients with rheumatic heart disease and prosthetic valves are discussed. These include the management of long-term anticoagulant therapy, prophylaxis against rheumatic fever and subacute bacterial endocarditis, impaired cardiac function, atrial fibrillation, breast feeding, and contraception as they relate both to the mother and the fetus and infant.

Adult↗

Long-acting hormonal contraception: assessing impact on bone density, weight, and mood.

The decline in unintended pregnancies and abortions in the United States has been attributed largely to increased use of two highly effective, hormonal contraceptive methods, depot medroxyprogesterone acetate injection (DMPA) and levonorgestrel implants (Norplant). Despite the efficacy and increasing acceptability of these long-term methods, some clinicians and women are reluctant to use them because of concerns regarding reduction in bone density with DMPA, and depressive symptoms and body weight issues with both injectables and implants. Recent multicenter experience showed no increase in depressive symptoms after 1 year's DMPA use and 2 years' Norplant use, even among users with the highest mean depressive symptom scores pre-therapy. Observational studies indicate that, as with other hormonal contraceptives and hormone replacement, DMPA does not cause significant weight gain, even during long-term use. Multicenter experience with the new soft-tubing Norplant product found an average annual pregnancy rate of <1% and a cumulative 5-year pregnancy rate of 4.2% in women weighing 70 kg or more--substantially lower than failure rates cited in the product labeling. Trends in bone density seen with DMPA appear similar to those during lactation. Subgroups of long-term DMPA users may experience a decrease in spinal bone density that appears to be reversible following discontinuation. A once-a-month injectable contraceptive combining 25 mg medroxyprogesterone acetate and 5 mg estradiol cypionate (Cyclo-Provera, Cyclofem or Lunelle), a 2-rod levonorgestrel system, and a single-rod 3-ketodesogestrel implant system may become available in the United States. Large-scale trials have established the safety, efficacy, and acceptability of Cyclo-Provera. In contrast to DMPA, users of Cyclo-Provera experience predictable, regular monthly bleeding, fewer discontinue due to bleeding-related problems. Fertility returns rapidly following discontinuation. A U.S. multicenter study is currently nearing completion.

Affect↗

Flowers of Hibiscus rosa-sinensis, a potential source of contragestative agent: I. effect of benzene extract on implantation of mouse.

In mouse, the benzene extract of Hibiscus rosa-senensis flowers was administered at four different dose levels (250-1000 mg/kg body weight/day) from day 1-4 postcoitus. Anti-implantation response and associated changes in the uterine chemical composition were studied. With an increase in the dosage of the extract, the percentage of implantation failure increased. At the dose level of 1 gm/kg body weight, the extract led to failure of implantation in 93% of the mice. The effect was accompanied by adversely altered uterine weight, its protein content and alkaline and acid phosphatase activity. In another experiment, influence of the extract on uterine uptake of progesterone was studied in bilaterally ovariectomized mice treated with or without estrogen. It exerted neither inhibitory nor stimulatory influence on uterine progesterone uptake in untreated castrated mice but the estrogen-induced increase in the uptake level was significantly inhibited by the extract. Failure of uterine bed preparation due to antiestrogenic potentiality of the extract has been discussed as the plausible cause of implantation failure.

Acid Phosphatase↗