Development of a reference material for analysing naturally occurring radioactive material from the steel industry.

Accurate measurement of naturally occurring radionuclides in blast furnace slag, a by-product of the steel industry, is required for compliance with building regulations where it is often used as an ingredient in cement. A matrix reference blast furnace slag material has been developed to support traceability in these measurements. Raw material provided by a commercial producer underwent stability and homogeneity testing, as well as characterisation of matrix constituents, to provide a final candidate reference material. The radionuclide content was then determined during a comparison exercise that included 23 laboratories from 14 countries. Participants determined the activity per unit mass for 226Ra, 232Th and 40K using a range of techniques. The consensus values obtained from the power-moderated mean of the reported participant results were used as indicative activity per unit mass values for the three radionuclides: A0(226Ra) = 106.3 (34) Bq·kg-1, A0(232Th) = 130.0 (48) Bq·kg-1 and A0(40K) = 161 (11) Bq·kg-1 (where the number in parentheses is the numerical value of the combined standard uncertainty referred to the corresponding last digits of the quoted result). This exercise helps to address the current shortage of NORM industry reference materials, putting in place infrastructure for production of further reference materials.

Molecular characterization of Buffalograss germplasm using sequence-related amplified polymorphism markers.

Buffalograss [ Buchloe dactyloides (Nutt.) Englem] germplasm has a broad resource of genetic diversity that can be used for turfgrass, forage and conservation. Buffalograss is the only native grass that is presently used as a turfgrass in the Great Plains region of North America. Its low growth habit, drought tolerance and reduced requirement for fertilizer and pesticides contribute to interest in its use. The objectives of this study were to use sequence-related amplified polymorphism (SRAP) markers in the evaluation of genetic diversity and phenetic relationships in a diverse collection of 53 buffalograss germplasms, and to identify buffalograss ploidy levels using flow cytometry. Based on their DNA contents, buffalograss genotypes were grouped into four sets, corresponding to their ploidy levels. Thirty-four SRAP primer combinations were used. This is the first report of the detection of differentiating diploid, tetraploid, pentaploid and hexaploid buffalograss genotypes, representing diverse locations of origin, using SRAP markers. Cluster analysis by the unweighted pair-group method with arithmetic averages based on genetic similarity matrices indicated that there were eight clusters. The coefficients of genetic distance among the genotypes ranged from 0.33 up to 0.99 and averaged D=0.66. The genetic diversity estimate, He, averaged 0.35. These results demonstrated that genotypes with potential traits for turfgrass improvement could readily be distinguished, based on SRAP. The use of PCR-based technologies such as SRAP is an effective tool for estimating genetic diversity, identifying unique genotypes as new sources of alleles for enhancing turf characteristics, and for analyzing the evolutionary and historical development of cultivars at the genomic level in a buffalograss breeding program.

Pregnancy in women with Kallmann's syndrome.

OBJECTIVE: To induce of ovulation and pregnancy in women with Kallmann's syndrome. DESIGN: Retrospective study. PATIENTS: Three women with hypogonadotropic hypogonadism and anosmia with a desire for pregnancy. INTERVENTIONS: Investigation of hypothalamic-pituitary-ovarian function and induction of ovulation by pulsatile GnRH or intramuscular human pituitary gonadotropins (hPG) or hMG with hCG. MAIN OUTCOME MEASURES: Successful induction of ovulation as measured by serum P levels and successful pregnancy. RESULTS: Ovulation was induced successfully in all three patients on more than one occasion and nine pregnancies occurred. Gonadotropin-releasing hormone was given IV by an electronically timed syringe driver. A total of 12 pulsatile GnRH cycles resulted in two pregnancies, 6 of these cycles being in one patient who did not ovulate or conceive with this therapy. Ovulation occurred in 10 of 16 hMG or hPG cycles, with conception in 7 of these. Gonadotropin usage was higher in these women compared with women with hypogonadotropic hypogonadism without anosmia (2,850 compared with 2,100 IU per treatment cycle), and the follicular phase was longer. CONCLUSIONS: All three women conceived and had children after induction of ovulation. The success rate of these therapies in Kallmann's syndrome appears to be high in spite of very few reports in the literature.

A comparative treatment trial of endometriosis using the gonadotrophin-releasing hormone agonist, nafarelin, and the synthetic steroid, danazol.

A randomized and double-blind trial was carried out comparing intranasal nafarelin acetate (400 micrograms daily) and oral danazol (600 mg daily), given over 6 months, in the treatment of 49 patients with laparoscopically proven endometriosis. Both drugs produced a highly significant and similar reduction (of 60 to 70%) in objective American Fertility Society scoring, even in severe disease. No effect was seen on adhesions. Both drugs suppressed oestradiol levels to a similar extent, although nafarelin caused a substantial rise in the first 2 weeks after the initiation of therapy. Nafarelin suppressed LH substantially and FSH, testosterone and prolactin to a small degree, whereas FSH and LH increased slightly during danazol. Pregnancies occurred in 12 of 22 infertile women in the 12 months following nafarelin, and in 6 of 14 in the danazol group. Side-effects were reported at a similar rate with both drugs, but the pattern was different. Hot flushes were the predominant side effect with nafarelin, although oestradiol levels were not suppressed to the extent expected. Small amounts of spotting or light bleeding were experienced with both drugs, but these tended to decrease with time with nafarelin and increase with danazol.

Autoimmune oophoritis: a clinicopathologic assessment of 12 cases.

Twelve cases of histologically confirmed autoimmune oophoritis are described. Eight presented with symptoms and laboratory evidence of premature ovarian failure (POF). Four were diagnosed unexpectedly after hysterectomy for endometrial pathology or for sequelae of cystic enlargement of the ovaries. Two of eight patients tested had serum anti-ovarian autoantibodies (Aab), while five of seven had anti-adrenal Aab. Two women had, or subsequently developed, Addison's disease, and two patients had Hashimoto's disease at presentation. All women with this disease risk the development of adrenal failure and hypothyroidism. Microscopically, 11 cases showed a lymphoplasmacytic infiltrate that spared primordial follicles but involved, with progressive intensity, early and late preovulatory follicles and corpora lutea. Sparse perivascular and perineural inflammatory infiltrates were also present. The twelfth case appeared to be a unique case of granulomatous oophoritis, considered autoimmune because of the folliculotropic nature of the inflammatory process. Three cases showed evidence of follicular dysplasia.

Sexual, reproductive and contraceptive risk factors for carcinoma-in-situ of the uterine cervix in Sydney.

Sexual, reproductive and contraceptive risk factors were investigated in a matched community-based case-control study of carcinoma-in-situ of the uterine cervix in Sydney. The risk was related strongly to the number of sexual partners: women who had had seven or more sexual partners in a lifetime had a six-fold increased risk compared with those with one or no partner. Early age at first sexual intercourse was also a risk factor, but this effect was reduced substantially after adjustment for the number of partners, with only a two-fold excess risk persisting for those with first intercourse before the age of 16 years as compared with those whose first sexual intercourse was at the age of 25 years or later. The long-term use of oral contraceptive agents was associated with an elevated risk (relative risk, 2.3 for more than six years of use); this effect was maintained for both oestrogen and progestogen doses. The risk increased with the number of induced abortions that had been undergone (relative risk, 2.2 for two or more abortions), but this effect was not statistically significant. A protective effect was found for women who had had a tubal ligation, for those who practised the rhythm method of birth control, and for women who breastfed. It is possible that these reduced risks may relate to unmeasured variables of life-style.

PIP: The extent to which sexual, reproductive, and contraceptive factors are associated with an increased risk of in situ cervical cancer was investigated in 117 Australian women with newly diagnosed cervical intraepithelial neoplasia type 3 and 196 matched controls. The risk of carcinoma in situ of the uterine cervix was found to increase from 4.5 for women with 2-3 sexual partners to 8.1 for those with 7 or more partners when compared to the risk for women with 1 or 0 partners. When these effects were adjusted for the other known risk factors of carcinoma in situ--age at 1st sexual intercourse, the duration of oral contraceptive (OC) use, and smoking--women who reported 2-3 sexual partners had an adjusted risk of 3.2, those with 4-6 partners had an adjusted relative risk of 4.2, and those with 7 or more had an adjusted risk of 6.3 compared to women with 1 or 0 partners. The effect of early age at 1st intercourse on the risk of carcinoma in situ was reduced substantially after adjustment for the number of sexual partners, with only a 2-fold excess risk persisting for those with 1st intercourse before the age of 16 years compared with those whose 1st intercourse occurred at 25 years of age or later. Longterm OC users were also found to be at increased risk of carcinoma in situ. Women with more than 6 years of OC use had an adjusted relative risk of 2.3 compared with never users. There were also increasing risks with increasing lifetime dosages of estrogen and progestogen. Risk increased to 2.2 for women who had undergone 2 or more abortions compared with women who had never had an abortion, but this effect was not statistically significant. Finally, a protective effect against carcinoma in situ of the uterine cervix was found among women who had undergone tubal ligation, those who utilized the rhythm method of fertility control, and women who breastfed; however, these reduced risks may be related to unmeasured life-style variables. No relationship was noted between the risk of carcinoma in situ and age at menarche, number of pregnancies, the age at 1st live birth, or the age at 1st breastfeeding.

Pulsatile intravenous gonadotropin-releasing hormone for ovulation-induction in infertile women. II. Analysis of follicular and luteal phase responses.

Pulsatile intravenous gonadotropin releasing hormone (IV-GnRH) was used in 36 infertile patients with primary amenorrhea (n = 5), secondary amenorrhea due to hypothalamic chronic anovulation (HCA) (n = 22), hyperprolactinemia (n = 1) or polycystic ovary syndrome (PCOS) (n = 5), and oligomenorrhea (n = 3), using several dosage and timing regimens. Early follicular phase responses showed four patterns: type 1 consisted of a delayed follicle-stimulating hormone (FSH) peak and was seen with severe hypothalamic suppression (n = 4); type 2 consisted of a brisk and dominant FSH peak on the first day of treatment, and occurred with mild to moderate hypothalamic suppression (n = 19); type 3, which consisted of an FSH peak accompanied by an immediate and exaggerated luteinizing hormone (LH) rise, occurred with mild PCOS and some cases of HCA (n = 5); and type 4, in which LH levels were high to begin with and neither FSH nor LH levels rose with GnRH, occurred with severe PCOS (n = 2). Exaggerated estradiol responses within 24 hours of therapy were seen in eight cycles: in four cases no ovarian abnormality was apparent; in three cases a dominant follicle was already present; and in one case ovarian hyperstimulation was diagnosed ultrasonographically. With standard human chorionic gonadotropin luteal phase support, luteal phase defects were rare with HCA but common with PCOS.

Statement on steroidal oral contraception.

PIP: This report summarizes a meeting of the IPPF International Medical Advisory Panel (IMAP) held in November, 1986, at which information on steroidal oral contraception (OC), Acquired Immunodeficiency Syndrome (AIDS), and female sterility were discussed. Regarding the multiphasic OC now in use, the benefits to health and well-being outweigh the possible side-effects and infrequent complications. Use is associated with a lower incidence of pelvic inflammatory disease, 96-98% effective prevention of pregnancy, a protective effect against ovarian and endometrial cancer, and regulation of erratic menstrual cycles. Minor side effects include nausea, vomiting, dizziness, headache, fluid retention, and inter-menstrual spotting. Adverse effects are circulatory system disease, myocardial infarction, venous thromboembolism, elevated blood pressure, and liver disease. Data on possible carcinogenicity have been conflicting. For women over age 40 OCs should be prescribed with caution. IMAP also drew up recommendations to assist FPAs to play a more active role in controlling the spread of AIDS. An effective program of Information and Education is of primary importance, targeting family planning workers and clients, teachers, parents, and employers. Wide promotion of condom use is a priority. Studies in Africa have revealed a major epidemic of AIDS, with the major mode of transmission heterosexual. The only immediate practical step in prevention of spread is by changes in sexual behavior. The last topic discussed is that of sterility in African women. The naturally occurring level of infertility expected in all populations of women is 3%; high levels in Africa vary by region from 3-32%. These levels of sterility are acquired through infection with Neisseria gonorrheae and Chlamydia trachomatis. Silent infection of women with Chlamydia make treatment especially difficult.^ieng

A case-control study of breast cancer in relation to the use of steroid contraceptive agents.

In a case-control study of 141 cases of breast cancer and 279 control patients from the Royal Prince Alfred and Westmead Hospitals during 1980-1982, we found similar risk factors to those reported for other populations. There was no statistically significant evidence of an increased risk of cancer from the use of oral contraceptive agents; the crude estimate of relative risk for patients who had used oral contraceptive agents at some time was 1.3 with 95% confidence limits of 0.8 and 1.9. After adjustment for other risk factors (age at first live birth, age at menarche, number of pregnancies, menopausal status, bilateral oophorectomy and years of education), the estimate of the relative risk of ever having used an oral contraceptive agent was 0.9 with 95% confidence limits of 0.6 and 1.5. Further analysis in terms of duration of use and dosage also provided no evidence of an increased risk.

Oral contraceptive agents.

PIP: The history of the development of oral contraceptives (OCs) has been a progressive reduction in dosage to what is now probably the lowest does that is compatible with the desired therapeutic effect -- to inhibit ovluation. Yet, controversy and argument continue. A table lists the OCs that are available in Australia. Many of these preparations, although having different trade names, have an identical composition. Since the withdrawal of sequential OCs from the Australian market, there are only 2 generic types. These are the progestogen only (mini) OCs, which consist of either 30 mcg of levonorgestrel or 350 mcg of norethisterone given at the same time every day; and the combined OCs, which contain an estrogen and a progestogen. In the last 12 months, some of the older high-dose OCs have been withdrawn, and it seems likely that further withdrawals will follow. Only 2 estrogens are used in the formulation of the OC, but there is a greater variety of progestogens. Ethinyl estradiol is used in most preparations. A small minority of OCs contain mestranol, the 3-methyl ether of ethinyl estradiol. Currently, there are only 4 OC agents that are available in Australia that contain mestranol and 2 of these contain the high doses of 100 mcg. Fundamentally, there are 2 types of progestogens -- those that contain, or are metabolized to, norethisterone and those that contain norgestrel or its close relative, desogestrel. With the exception of the norgestrel group and desogestrel, all other progestins, including norethisterone itself, are effective in vivo after they have been metablized to norethisterone. Mestranol is effective in humans after demethylation to ethinyl estradiol. In the norgesterel group, since d-norgestrel is inert endocrinologically, 250 mcg of levonorgestrel and 500 mcg of dl-norgestrel are equivalent. Levonorgestrel and desogestrel are of approximately equal potency. With the combined OC agents, the overwhelming mechanism of action is by the inhibition of the midcycle peak of luteinizing hormone (LH) secretion and, hence, the inhibition of ovulation. Progestogen-only OCs have additional actions such as effects on cervical and fallopian tube mucin. Minor side-effects include disturbance of the menstrual cycle, changes in weight, and changes in mood. Major side-effects relate to 4 areas -- subsequent reproduction, the cardiovascular system, other metabolic effects, and the risk of malignancy. A table presents the absolute contraindication contraindications. There is not the slightest doubt that a woman who is over 35, who smokes, and who, in addition, may be obese and has hypertension should not use OCs. Progestogen (mini) OCs have a slightly higher failure rate and a greater incidence of irregular bleeding than have combined OCs. The mini OC has little place in women who need effective hormonal contraception and good cycle control. The mini OC may have a place in a patient who finds other contraception unacceptable and in whom estrogens are contraindicated specifically.^ieng

Clinical experience with 50 cases of first-trimester fetal diagnosis by chorionic biopsy.

Prenatal diagnosis by chorionic biopsy was undertaken between the eighth and 12th weeks of pregnancy in 50 patients at risk of chromosomal or genetic abnormalities. Samples from 45 patients were karyotyped. A DNA analysis for the detection of homozygous beta-thalassaemia was undertaken in five patients. The sample from one patient at risk of haemophilia in the fetus was subjected to DNA analysis after a male fetus was confirmed on karyotyping. Abnormal karyotypes were detected in four fetuses while three had homozygous beta-thalassaemia.

Familial hyperinsulinemia complicated by extreme insulin resistance during pregnancy: a probable postreceptor defect.

Detailed studies of a family with hyperinsulinemia are reported. The index patient, a 30-yr-old woman with polycystic ovary syndrome, presented with gestational diabetes which was completely resistant to insulin in the presence of severe endogenous hyperinsulinemia. Sensitivity to insulin was regained after delivery. Therapy with cyproterone acetate and ethinyl estradiol for hirsutism exacerbated the hyperinsulinemia toward the levels occurring in pregnancy, with a concomitant deterioration of glucose tolerance. Five other members of her family also were found to have hyperinsulinemia together with high concentrations of circulating C-peptide. Antibodies to insulin and to insulin receptors were not detected, insulin antagonists were not increased, and insulin degradation in the circulation was normal. Insulin extracted from the patient's serum was identical to normal insulin by the criteria of Sephadex chromatography, placental membrane insulin receptor binding, and stimulation of 2-deoxyglucose uptake in isolated rat adipocytes. Although [125I]insulin binding to erythrocytes of all family members and to the patient's placental membranes was markedly reduced, binding to fibroblast cultures from the patient was normal. Insulin-stimulated glucose transport in these fibroblasts also was normal, but there was a mild (20%) reduction in the concentration of cytochalasin B-binding sites in erythrocyte ghosts. Insulin resistance in this family may be due to a partial defect distal to the insulin receptor. This is asymptomatic unless metabolic stresses (pregnancy or steroid administration) are superimposed.

Ultrasound guided chorion biopsy in antenatal diagnosis of genetic disorders.

The technique of transcervical chorion biopsy was evaluated in women about to undergo therapeutic termination of pregnancy. The trophoblast biopsy catheter (Portex) under real-time ultrasound guidance was the most reliable in obtaining chorionic villi. The overall success rate for chorion biopsy was 73% in the first 100 patients studied.

Gynaecological importance of unusual pituitary tumours.

Sixty-eight women with pituitary tumours exhibiting gynaecological symptoms have been reviewed. Fifty-two tumours were prolactinomas while 6 were growth hormone secreting, 6 ACTH secreting, 1 was a large 'inert' adenoma and 3 were late-presenting craniopharyngiomas. Several of the prolactinomas exhibited unusual features including excessively high prolactin secretion, a wide spectrum of sensitivity to bromocriptine, rapid expansion in pregnancy, association with the empty sella syndrome and even a secondary malignancy. The behaviour of tumours secreting other hormones but presenting with gynaecological symptoms is described.

Oral contraceptives.

PIP: 4 kinds of progestin only oral contraceptives (OCs) and numerous combined OCs containing ethinyl estradiol (EE) or occasionally mestranol and either norgestrel or norethindrone are currently available in Australia. All progestins except norgestrel are effective in vivo after metabolism to norethindrone. Mestranol is effective in the human after demethylation to EE. The main side effects of OCs, including menstrual disturbances and changes in weight and mood, are primarily of nuisance value. Menstrual blood loss with OCs is almost invariably less than during spontaneous menses, but breakthrough bleeding and midcycle spotting may cause concern in patients. Amenorrhea and weight gain are rare with low dose pills. Approximately 6 in 1000 women remain anovulatory for 12 months or more after discontinuing OCs, but it is not yet know whether the amenorrhea is related to pill use and it is usually corrected by induction of ovulation. Cardiovascular side effects including venous thrombosis and pulmonary embolism are seen less frequently with new lower dose pills. The effects of OCs on the cardiovascular system are complex and depend on the interaction of estrogen and progestin. Amounts of estrogen and progestin should be the lowest possible to prevent ovulation, and routine monitoring should be provided for all women using pills. Older high dose formulations altered lipid metabolism in the direction of greater risk of coronary heart disease. Although research suggests the lowest dose triphasic pills have no significant effect, not enough large studies have been done with matched controls. Any effects on carbohydrate metabolism of the low dose pills are apparently minor and of little clinical significance. Insulin dependent diabetics with adequate supervision may safely use low dose pills. Combined OCs reduce the incidence of endometrial and ovarian malignancy. No relationship between OCs and the risk of breast cancer has been demonstrated except possibly in women under 35 when the cancer developed. The risk of intraepithelial neoplasia may be increased in women taking OCs for more than 8 years. Data on drug interactions are inconclusive, but women on rifampicin should use some other method. Absolute contraindications to OCs include breast cancer, history of deep venous thrombosis or pulmonary embolism, active liver disease, use of rifampicin, familial hyperlipidemia, previous arterial thrombosis, and pregnancy, while relative contraindications include smoking, age over 35, hypertension, breastfeeding, and irregular spontaneous menstruation. Progestin only OCs have a higher rate of failure and irregular bleeding than combined pills and their main use is for breastfeeding women and those with contraindications to estrogen. The pill of 1st choice should be a triphasic low-dose formulation.^ieng

Cyproterone acetate and the treatment of hirsutism.

Forty-two women with hirsutism completed 12 months of treatment with cyproterone acetate and ethinyl oestradiol given in a reverse sequential regimen. A highly significant improvement was recorded in the whole group using the Ferriman and Gallwey scoring system. Ten patients recorded a poor response whereas 19 recorded a good or very good result. Patients from groups with polycystic ovarian disease and idiopathic hirsutism recorded equally beneficial responses. Fasting plasma triglycerides rose significantly after 12 months. Other lipids were largely unaffected although a small fall in high density lipoprotein-cholesterol was detected at mid-cycle. No other biochemical abnormalities were found. Circulating levels of testosterone and 17 hydroxyprogesterone were suppressed during treatment. Side-effects were not prominent. This appears to be a very useful medication for a clinical problem which hitherto has been difficult to treat.

Premature hypergonadotropic ovarian failure: clinicopathological study of 19 cases.

During the 5-year period 1977-1982, 57 patients below 35 years of age with secondary amenorrhea were assessed for hypergonadotropic (primary) ovarian failure. The histological findings within the ovaries as well as pertinent clinical and laboratory correlates are described. Nineteen had diagnostic ovarian biopsies performed. The importance of this technique is stressed. The ovaries of 14 patients showed absence of primordial follicles (true premature menopause); three others showed "resistant ovary syndrome" characterized by the presence of primordial follicles but little or no follicular development (including a case of galactosemia, in which the associated ovarian failure has been ascribed to follicular atresia). The remaining two revealed florid chronic perifollicular inflammatory reactions in the presence of both primordial and also developing follicles--one lymphoplasmacytic and the other granulomatous. The former has been previously suggested as evidence of an autoimmune process, but the latter has not hitherto been reported.

Efficacy of mefenamic acid in patients with a complaint of menorrhagia.

Sixty-nine patients with a convincing history of menorrhagia completed a 4-cycle double-blind randomized placebo-controlled crossover trial of mefenamic acid taken during menstruation. Only 30 of these patients demonstrated objective menorrhagia with a measured menstrual loss greater than 80 ml during the placebo cycles, but the remainder reported passing clots and/or using 2 pads at a time. Fourteen of these women (20%) had a loss of less than 35 ml while taking placebos. This raises serious questions about the establishment of menorrhagia based on history alone. Overall, there was a mean reduction of 28.1% in menstrual blood loss between placebo and mefenamic acid cycles (P less than .001). The greatest reduction recorded was 80%, and most of the large percentage reductions were seen in patients with high loss during placebo cycles. Significant reductions in blood loss (P less than .001) were seen in patients with ovulatory dysfunctional uterine bleeding and menorrhagia that developed after tubal interruption. There was also an indication based on small sample sizes that mefenamic acid reduced blood loss in women with anovulatory dysfunctional uterine bleeding, fibroids, intrauterine devices, and von Willebrand disease. No reduction was seen during the mefenamic acid cycle in the group with a loss of less than 35 ml during the placebo cycle. There was a significant shortening of duration of bleeding (P less than .003). Fifteen patients (21.7%) experienced no objective reduction in blood loss.

Oral contraceptives: where are the excess deaths?

In the 1960s and 1970s a substantial body of data was published indicating an excess death rate, mainly related to a cluster of cardiovascular complications, in women who either were taking or had ever taken oral contraceptives. The epidemiological interpretation of these data has been seriously questioned, and many workers now think that the excess deaths in these women are almost entirely attributable to smoking. In addition, it is clear that the death rate from myocardial infarction in women in Australia, which has declined significantly in the last twelve years, is quite different from that seen in women in the United Kingdom, where the death rate from myocardial infarction continues to increases. The validity of basing warnings, contraindications and advice to patients regarding the use of oral contraceptives on data from different populations should be reconsidered.

PIP: In the 1960s and 1970s, a substantial body of data was published indicating an excess death rate, mainly related to a cluster of cardiovascular complications, in women who either were taking or had ever taken (OCs) oral contraceptives. The epidemiological interpretation of these data has been seriously questioned, and many workers now think that the excess deaths in these women are almost entirely attributable to smoking. In addition, it is clear that the death rate from myocardial infarction in women in Australia, which has declined significantly in the last 12 years, is quite different from that seen in women in the United Kingdom, where the death rate from myocardial infarction continues to increase. The validity of basing warnings, contraindications, and advice to patients regarding the use of OCs on data from different populations should be reconsidered.