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Summary Microanalytical techniques for the measurement of pituitary gonadotrophins and ovarian steroid hormones have been applied to disorders of the H.P.O. axis in recent years. The integrity and functional capacity of the individual components can be investigated using clomiphene, synthetic gonadotrophinreleasing hormone (Gn-RH), gonadotrophins and oestradiol-17β. The majority of patients presenting with oligomenorrhoea or amenorrhoea have a functional suppression of the hypothalamus resulting in a failure of GnRH synthesis and/or release. The basic endocrine pathology of polycystic ovarian disease is still unknown although abnormalities in the function of all parts of the H.P.O. axis can be demonstrated. Partial or complete failure of the positive feedback effect of oestradiol appears to be relatively common and results in failure of ovulation with infertility and an upset in menstruation. With the investigative techniques now available it should be possible in the near future to classify disorders of menstruation on the basis of their underlying pathology.

The changes in unconjugated estradiol-17beta and estriol, progesterone and chorionic somatomammotropin (HCS) in peripheral plasma have been studied in 18 women at 30-minute intervals following intra-uterine prostaglandin E2 administration for therapeutic termination of second trimester pregnancy. The hormonal changes were related to the time of fetal death detected by the disappearance of fetal heart pulsations. Prostaglandin E2 was given by the intra-amniotic route with urea (5 patients) or with intravenous oxytocin (5 patients), or by the extra-amniotic route with intravenous oxytocin (8 patients). Fetal death occurred rapidly with intra-amniotic PGE2, but usually at a late stage with extra-amniotic PGE2. Three fetuses in the extra-amniotic group died at or just before abortion. A variety of fetal heart changes were noted and the time of fetal death did not appear to influence the time of abortion within each treatment subgroup. Estradiol and estriol showed a sligh but persistent fall over 24 hours prior to induction of abortion. A more rapid fall usually occurred after induction, with a consistent fall around the time of fetal death. Progesterone and HCS usually fell much less before and immediately after fetal death. A marked rise in estradiol sometimes occurred before fetal death, particularly in the intraamniotic PGE2 and urea subgroup. Estriol levels declined more rapidly before than after fetal death, whereas fetal death had less consistent effects on the other hormones. All hormones had usually fallen considerably at the time of abortion, and in some individuals marked fluctuations in hormone levels were seen.

Summary The outcome of 82 pregnancies associated with failure of an intrauterine device is reported. Four of the pregnancies were extrauterine, and 31 per cent of the 78 intrauterine pregnancies were legally terminated. Spontaneous or missed abortion occurred in 57 per cent of the remainder and over half of these abortions were in the second trimester. Threatened abortion, antepartum haemorrhage and manual removal of an adherent placenta were encountered more frequently than expected. One neonatal death due to prematurity was recorded, and there was one congenital fetal abnormality.

We describe four females from three families with blepharophimosis, epicanthus inversus, and ptosis who were found to have premature ovarian failure. In two families the inheritance was autosomal dominant and in one it was a new mutation. Two females had, in addition, dysmorphic facial features which have been described in other cases. We suggest that the aetiology of the blepharophimosis ovarian failure syndrome is a contiguous gene syndrome.

A review is presented of the existing literature on the progestogen-only "mini-pill", a greatly under-used method of contraception. The under-use appears to stem from a lack of awareness on the part of medical advisers of the reasonable efficacy and minor side effects of the method. The benefits and disadvantages have been carefully evaluated and recommendations made for the more widespread use of progestogen-only mini-pills.The progestogen-only minipill is used by few of the 50 million women worldwide who use oral contraceptives. This review deals mainly with minipills containing norethindrone (NET) 350 mcg or levonorgestrel (LNG) 30 mcg. The minipill exerts its antifertility influence at the endometrial, ovarian, tubal ephithelial, follicular, and luteal levels as well as on the cervix and cervical mucus. Although some earlier trials indicated pregnancy rates of 1.4-4.3/100 woman years, later combined pregnancy rates in trials of 5 different progestogen-only pills varied from .9-3 pregnancies/100 woman years. Recent indications show, in general large scale usage, minipill pregnancy rates similar to that of combined pills. Several small studies show an increase in the proportion of ectopic pregnancies in minipill users. Variability of menstrual cycle lengths is a controversial aspect of the minipill. In 2 studies using NET and norgestrel, 46-66% of cycles fell in the 25-35 day range. Vaginal bleeding lasted 4-6 days in 78% of cycles. 20-30% of patients notice spotting or breakthrough bleeding, which occurs in 5.8-16.2% of cycles. Intermenstrual bleeding problems are a major concern with progestogen-only methods, and prospects for avoiding the problem completely are limited. The progestogen-only minipill appears to cause no deterioration in carbohydrate tolerance, to have little or no effect on blood lipids and to cause no detectable change in liver function, blood clotting and platelet aggregation, thyroid function, or pituitary-adrenal responsiveness. There is no evidence linking LNG or NET used as a minipill to breast, cervix, or endometrium cancer. Progestogen may protect against endometrial cancer. No cases of congenital abnormality have been reported in babies born to women taking the minipill at conception. Progestogen tends to have no effect on breast milkvolume or may cause a slight increase. No effect of progestogen taken by the lactating mother has been demonstrated on the health or growth rate of the baby.

Summary: 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.

Acute and severe menorrhagia necessitating emergency hysterectomy is a rare occurrence. It is occasionally encountered in women with systemic coagulation disorders (I), but hardly ever in other situations. This report describes an unusual case of menorrhagia associated with unexpected damage to a cervical artery.

Four cases are described of a very rare association among blepharophimosis, resistant ovary syndrome, and true premature menopause. Plasma levels of follicle-stimulating hormone and luteinizing hormone were significantly elevated and estradiol significantly decreased in all four cases. Ovarian biopsies demonstrated large numbers of unstimulated primordial follicles in three cases and no follicles in one case. Two of the four women were sisters, with the older having true premature menopause and the younger having resistant ovary syndrome. The explanation for the association of blepharophimosis with primary ovarian dysfunction is unknown, but the possibility of a microdeletion of genetic material containing two geographically associated but independent genes could not be confirmed or excluded by high-resolution chromosome banding. All families affected by the autosomal dominant condition of blepharophimosis should be counseled about the high incidence of ovarian dysfunction and female infertility, at least in one form of the syndrome.

A 13-year-old girl presented because of abnormal pubertal development. She was found to have an isochromosome of 22 in addition to a normal female chromosome complement. Investigation also showed moderate mental retardation.

Initial discussion in this health perspective on hormonal contraceptives is directed initially to combined estrogen-progestogen oral contraceptives (OCs) providing a medical and social perspective and then reviewing the literature concerning the side effects of cardiovascular diseases neoplasia congenital defects metabolic effects the less serious conditions which may be caused or precipitated by OC use and the positive and negative medical aspects. The discussion then turns to the risk perspective methods of evaluating risks and minimizing contraceptive risk and improving safety. Overall disease of the circulatory system is the most important deleterious effect of combined OC use. Yet deaths from cardiovascular disease are the most easily preventable of OC complications since at least half of the deaths would be prevented if women did not smoke cigarettes. The risks are dramatically concentrated in women aged over 40 years and to a lesser extent over 35 years who smoke cigarettes and who have other cardiovascular risk factors such as hypertension hyperlipidemia a strong family history of cardiovascular disease or who have diabetes. Despite strenuous efforts on the part of various journalists to persuade otherwise at this time there is no clear evidence that use of combination OCs predisposes to any type of malignancy. A small number of studies have pointed towards a very low grade risk of certain congenital anomalies in women who are inadvertently exposed to OCs during the early part of pregnancy. Since the trends are not confirmed in all studies it is not absolutely clear that OCs actually do contribute to some congenital anomalies. There is now good evidence to indicate that the incidence of gall bladder disease is about doubled during the 1st year of OC use. There is no evidence of a continuing effect. Liver diseases which may be precipitated or exacerbated by OC use include severe congenital enzyme defects obstetric cholestasis porphyria and active hepatitis. Prolonged post pill amenorrhea occurs in about 3-5/1000 users. There is now good evidence that combined OCs reduce milk volume in lactating women and they also produce some changes in milk composition. A wide range of metabolic changes have been demonstrated by laboratory tests. Most of these are dose related and have been minimized by the modern trend toward very low dose steroidal preparations. The aim is to identify those women who initially have high risk factors for hormonal contraceptive use or who develop risk factors or complications during use. Overall combined OCs and long acting progestogen-only methods show a high benefit to risk ratio in all but a small number of high risk women. For the great majority of women the combined OC appears to be 1 of the safest medications which can be taken on a longterm basis.

A comparative analysis of microvessel concentration in 24 specimens of normal human endometrium has been carried out in the mid-proliferative (n = 12) and mid-secretory (n = 12) phases of the menstrual cycle, with the finding of a significantly greater vascularity in the mid-secretory phase (25.0+/-12.7 microvessels/sq mm compared with 12.2+/-6.3; mean +/-SD; p

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.

The concentrations of oestrone and oestradiol as measured by a double isotope derivative method in fluid from Graafian follicles at different phases of the menstrual cycle were compared to the corresponding concentrations in ovarian and peripheral venous plasma collected simultaneously. In follicular fluid the concentration of oestradiol was much greater than that of oestrone. The concentrations of oestrogens were similar in fluid collected from small follicles at all phases of the cycle. The concentration of oestradiol in large follicles (greater than 1 cm diameter) was much higher in the mid-late follicular phase of the cycle (mean = 5390 plus or minus 1330 nmol/l) than in large or small follicles at other phases of the cycle. In the mid-late follicular phase of the cycle large follicles were invariably associated with high concentrations of oestradiol in venous plasma draining the corresponding ovary (mean 49 plus or minus 12 nmol/l). The mean ratio of oestradiol/oestrone in fluid from large follicles in which the concentration of oestradiol was greater than 1400 nmol/l (18.0 plus or minus 1.0, n = 10) was significantly higher than the ratio in corresponding samples of ovarian venous plasma (10.7 plus or minus 1.4, n = 11). These findings suggest that when the concentration of oestradiol in a Graafian follicle exceeds 3500 nmol/l it is likely to be functionally active.

It is estimated that 60% of Australian couples will opt for sterilization as a method of birth control. Approximately 0.5 to 1% of all sterilized males and females will request reversal. With tubal occlusion, it appears that the method used to produce occlusion, the occlusion site, the length of viable tube remaining and the time between sterilization and reversal appear to be predictive factors in producing intrauterine pregnancy. With the increasing tendency for sterilization to be performed in younger women, surgeons should consider performing surgery only on the isthmus of the tube, preserving as much undamaged tube as possible and using methods of occlusion other than diathermy to ensure adequate tubal occlusion and yet maintain optimum conditions should reversal be required. Successful pregnancy following vasovasostomy appears to be related primarily to length of time elapsed following vasectomy and to the skill of the surgeon in the use of microsurgical techniques, possibly aided by preservation of nerve supply to the vas. It is doubtful whether the presence of sperm antibodies in serum or semen will affect the return of fertility in most individuals, but further research is required to clarify this.

Uterine blood flow rates were obtained with a Krypton (85Kr) clearance technique and with radio-active microspheres in six anaesthetized, non-pregnant ewes (a total of ten comparisons). 85Kr was administered, via a catheter, into the abdominal aorta and beta-emissions were detected with a catheter-type semi-conductor detector probe situated in the lumen of a uterine horn. In seven instances, the 85Kr clearance curve had only one component while in the remaining three instances the curves could be resolved into two components. The flow rates derived from the single component curves and the mean flow rates calculated from the curves with two components were of the same order as, and highly correlated with, estimates of capillary blood flow obtained with microspheres for either the caruncles, the inter-caruncular endometrium or the total endometrium (r = 0.832, r = 0.822 and r = 0.841, respectively, P less than 0.005). There was no correlation between the flow rates obtained with the 85Kr technique and estimates of myometrial capillary blood flow obtained with microspheres.

SUMMARY A continuous isotope infusion technique was used to measure the metabolic clearance rate (MCRB) and production rate (PRB) of oestradiol-17β in a group of six non-pregnant conscious Chinchilla rabbits. The mean MCRB of oestradiol was 162 ml/min (0·079 1/ min/weight0·75), and at equilibrium a significant proportion of the radioactivity in the circulation was present as oestrone (conversion ratio oestradiol to oestrone, 27·6%). The mean PRB of oestradiol was 4·3 ng/min, which is equivalent to about 5 μg/day. Some day-to-day variation was seen in the endogenous concentrations of oestradiol, oestrone and progesterone although in general the levels of the two oestrogens were less than 30–40 pg/ml, and progesterone levels were below 300 pg/ml apart from short peaks up to 600 pg/ml. These values were compared with previous measurements of the ovarian secretion rate of oestradiol measured directly in anaesthetized animals.

Peripheral plasma concentrations of 13, 14-dihydro-15-keto prostaglandin F 2 α (PGFM) were measured in seven women having elective cervical encerclage in an otherwise normal pregnancy. Three of seven patients had a statistically significant elevation of PGFM levels at 60 minutes after commencement of surgery. On the basis that the majority of patients had no significant rise and that there was no objective evidence of uterine contractions post-operatively, the routine administration of prostaglandin inhibitory agents to patients having cervical encerclage cannot be recommended.

Summary: Eleven women were referred with postabortal amenorrhoca and cyclical lower abdominal pain due to upper cervical occlusion by a thin band of fibrous adhesions. All had undergrone first trimester termination of pregnancy by vacuum curettage. Associated intrauterine adhesions were found in 2 patients. Cervical adhesions were easily breached with a uterine sound and cervical dilators, and were then visualized with a hysteroscope. All women resumed normal menstrual cycles and suffered no sequelae. This unusual, but eminently treatable, complication of vacuum curettage should be more widely appreciated.

The presence and significance of locally produced antisperm antibody in 20 well-documented infertile patients has been investigated. Sera and vaginal washings both from patients and from fertile controls were examined for antisperm antibody by means of four methods. Antisperm antibody was detected in 25% of the washings taken from infertile patients, but in none of those from fertile women. Detection of antibody by the microimmobilization technique discriminated best between infertile and fertile women both in serum (P=0.0166) and in washings (P=0.0166). The results of this study support the concept that locally produced antisperm antibody contributes to conception failure in a subgroup of infertile women, and that the routine study both of sera and of vaginal washings of infertile patients has practical value.20 women (mean age, 32 years) with infertility of at least 12 months duration (mean duration of infertility, 4.2 years) were studied to determine antisperm antibody in local secretions of infertile women. 33 fertile women who had just delivered 6-8 weeks before comprised the controls (mean age, 24.2 years). Antisperm antibody was detected using 4 techniques: 1) microagglutination tray test by Frieberg; 2) tube-slide microagglutination test by Franklin and Dukes; 3) microimmobilization test of Isojima as modified by Boettcher; and, 4) indirect immunofluorescent test of Hjort and Hansen. Cervical and vaginal washings were obtained from the subjects using the method of Waldman. Sperm samples of good quality (sperm count of about 6 x 10 to the seventh/ml; good motility of at least 70%; abnormal forms of less than 30%) were used. Antisperm antibody was found in the cervical-vaginal washings of 25% of the infertile patients and none in the fertile group. The sperm microimmobilization testwas the most discriminating test, giving positive results in the sera/washings of 20% of the infertile patients, and negative results in both the serum/washings of all controls (P=0.0166). The findings confirm the role of antisperm antibody in the conception failure of a subgroup of infertile women.

A prospective study of the menstrual pattern and weight changes was made in the first year of training of 29 new female entrants to a professional ballet school. Seventy-nine per cent of the student girls had menstrual disturbances at entry: primary amenorrhoea, four; secondary amenorrhoea, 11; irregular menses, eight. The incidence of secondary amenorrhoea increase substantially by the end of the year (20), but was not associated with any significant change in body weight. Only three students menstruated regularly during the year. Menstrual regularity improved during periods of injury and long vacation and it appears that deterioration of the menstrual pattern during dancing periods was related to strenuous physical exercise rather than to any change in body weight.

Numerous studies have been made of the lymphatics in normal human endometrium but, due to the methods used, the investigators were only able to demonstrate the larger vessels found in the deeper regions. In this report, lymphatics in the superficial layers are described. They form an extensively anastomosing network of fine vessels which extend almost to the surface epithelium and are structurally similar to the small lymphatics found elsewhere in the body. These vessels form terminations which may be the sites of upward growth as the endometrium thickens during the menstrual cycle. The superficial lymphatics may be involved in the process of remodeling of the endometrium which occurs during menstruation.

Ovarian function was assessed in two women with congenital absence of the uterus, Fallopian tubes and vagina, by the estimation of total estrogens, pregnanediol, luteinizing hormone and follicle stimulating hormone in urine every day for 61 and 88 days, respectively. The patterns of hormonal excretion were within normal limits with cycle lengths varying from 30 to 34 days. These findings confirm that normal cyclical ovarian activity can occur in the absence of the uterus or other Mullerian duct tissue in women.

Summary The occurrence of cystic glandular hyperplasia of the endometrium in adolescent girls has been reviewed. This condition has been diagnosed much less frequently in the South-Eastern Region of Scotland than in previously reported series. Only 5.3 cases per year were diagnosed in a population of 1 100 000 in a ten-year period. This represented 4.0 per cent of all cases of abnormal uterine bleeding requiring curettage in adolescent girls in the region, and 1.9 per cent of cases of cystic glandular hyperplasia from all age groups. Mild hyperplastic changes were found almost as frequently as the more classical “Swiss-cheese” cystic glandular hyperplasia. Patients showing more marked hyperplastic changes had a worse prognosis than those who only showed mild changes, in particular a high incidence of persistent menstrual abnormalities, repeated curettage, repeated hormone therapy, primary infertility and possible polycystic ovarian disease. The implications of the finding of cystic glandular hyperplasia in adolescent girls have been discussed.

SUMMARY In nine men, spermatic and peripheral venous plasma was collected at operative repair of varicocele or inguinal hernia. The concentrations (ng/100ml plasma ± s.e.m.) of both oestradiol-17β (208 ± 28) and oestrone (36 ± 5) were higher than the corresponding values in peripheral venous blood (oestradiol, 3·2 ± 0·5; oestrone, 7·4 ± 1·5). These results confirm that both oestrogens are secreted directly by the testis.

Pituitary-ovarian relationships were assessed over a 3-month period in 4 patients with adolescent dysfunctional uterine bleeding by serial measurements of estrogen and pregnanediol excreted in the urine, and plasma concentrations of LH and FSH. Three of the 4 patients showed two spontaneous anovulatory cycles with marked increases in estrogen excretion but with a failure of the normal midcycle surge of LH. Clomiphene initiated a rise in plasma FSH and LH with subsequent follicular development suggesting that the negative feedback relationship between estrogens and gonadotropins was intact. The concentrations of estradiol-17β and estrone in peripheral venous plasma were within normal limits for women in the reproductive age group. These results suggest that the absence of ovulation in these patients may be associated with a failure to discharge LH in response to increasing levels of estrogen.

Dysfunctional uterine bleeding (DUB) is excessively heavy, prolonged or frequent bleeding of uterine origin which is not due to pregnancy or to recognisable pelvic or systemic disease. Anovulation may be inferred from a number of observations but, in the normal clinical situation, anovulation is often assumed when a woman presents with heavy, prolonged or frequent bleeding, particularly in those who are at the extremes of reproductive life and in women known to have polycystic ovarian syndrome. Menstrual bleeding that is irregular or excessive is poorly tolerated by the majority of women. Changes in the length of the menstrual cycle generally imply disturbances of the hypothalamo-pituitary-ovarian (HPO) axis. In anovulatory DUB with acyclic (irregular) oestrogen production there will be no progesterone withdrawal from oestrogen primed endometrium and so cycles are irregular. Prolonged oestrogen stimulation may cause a build up of endometrium with erratic bleeding as it breaks down and is expelled. This is the rationale for using cyclical progestogens during the second half of the menstrual cycle, in order to provoke a regular withdrawal bleed. Continuous progestogen is intended to induce endometrial atrophy and hence to prevent oestrogen-stimulated endometrial proliferation. Progestogens, and oestrogens and progestogens in combination are already widely used in the management of irregular or excessive bleeding due to DUB but the regime, dose and type of progestogen used varies widely, with little consensus about the optimum treatment approach.To determine the effectiveness and acceptability of progestogens alone and oestrogens and progestogens in combination in the management of irregular bleeding associated with anovulation.We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched 4 May 2007), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to May 2007), EMBASE (1985 to May 2007), CINAHL (1982 to May 2007), Biological Abstracts (1969 to May 2007), Current Contents (1980 to 2007) and reference lists of articles.All randomised controlled trials of progestogens (via any route) alone or in combination with oestrogens in the treatment of irregular bleeding associated with anovulation.Study quality assessment and data extraction were carried out independently by two review authors. Both authors were experts in the content matter.No randomised trials were identified which compared progestogens with oestrogens and progestogens or with placebo in the management of irregular bleeding associated with anovulation. Only one small, non-randomised study compared two progestogen regimes in the management of heavy and irregular bleeding in women with confirmed anovulation. One randomised study compared the effects of two progestogens on endometrial histology in women with a variety of menstrual symptoms, half of whom had cystic glandular hyperplasia.There is a paucity of randomised studies relating to the use of progestogens and of oestrogens and progestogens in combination in the treatment of irregular bleeding associated with anovulation. Further research is needed to establish the role of these treatments in the management of this common gynaecological problem.

Recent research has not been able to demonstrate close endometrial morphological correlations with specific abnormalities of menstrual bleeding, but has pointed to an increasing number of molecular mechanisms that may be involved in the occurrence of certain forms of abnormal uterine bleeding. Ovulatory and anovulatory dysfunctional uterine bleeding (DUB) and progestogen-related breakthrough bleeding (BTB) are three conditions with quite different clinical characteristics. It is also probable that the local endometrial molecular mechanisms associated with these three menstrual disturbances are quite different. Ovulatory DUB is associated with a series of vascular and haemostatic disturbances that all appear to contribute to increased loss of blood and tissue fluid at menstruation. Anovulatory DUB is associated with obvious disturbances of endometrial histology, vascular morphology and fragility, with variable and increased blood flow. Progestogen-related BTB is associated with a multitude of morphological and functional endometrial changes that appear to relate predominantly to a patchy capillary origin for the bleeding. Many molecular and cellular changes have been observed in all three conditions. It is not yet known whether there is a single, but different, underlying mechanism responsible for these multiple abnormalities in each of the three clinical situations.A review of recent research indicates that three forms of abnormal uterine bleeding, ovulatory and anovulatory dysfunctional uterine bleeding and progestogen-related breakthrough bleeding, are associated with different local endometrial molecular mechanisms. Moreover, the wide variety of local substances that control endometrial breakdown and repair are altered by circulating concentrations of exogenous and endogenous steroid hormones. Ovulatory dysfunctional uterine bleeding is associated with a series of vascular and hemostatic disturbances that all appear to contribute to increased loss of blood and tissue fluid at menstruation. Anovulatory dysfunctional uterine bleeding is associated with obvious disturbances of endometrial histology, vascular morphology, and fragility, with variable and increased blood flow. Progestogen-related breakthrough bleeding is associated with a multitude of morphological and functional endometrial changes that appear to relate predominantly to a patchy capillary origin for the bleeding. It remains unclear whether there is a single but different underlying mechanism responsible for these multiple abnormalities in each of the three clinical situations. A greater understanding of these mechanisms has the potential to increase use of effective contraception since menstruation disorders are the most frequent cause of method discontinuation.

The chick chorioallantoic membrane assay has been used for many years as an in vivo assay of angiogenic activity. However it has been plagued with the problem of a high incidence of false positive angiogenic responses. In this study the conventional chick chorioallantoic membrane assay was compared with a modification of this technique in a series of batches using a total of 100 eggs. False positive reactions were recorded in 32 out of 50 (64%) using the conventional method and only 11 out of 50 (22%) with the modified method (chi 2 = 17.992; p less than 0.001).

The aim of this study was to develop an objective test for superficial endometrial vascular fragility at hysteroscopy, and to apply this test to women using Norplant((R)) for contraception and to women with ovulatory dysfunctional uterine bleeding (DUB). A prospective observational study was carried out in 34 Norplant users and 20 women with menorrhagia due to ovulatory DUB. Superficial endometrial vascular fragility was assessed at hysteroscopy by observing the source and extent of frank and subepithelial bleeding during controlled collapse and redistension of the uterine cavity. Superficial endometrial blood vessels were more fragile in Norplant users compared to women with DUB (chi(2) = 11.60, P = 0.02). Superficial endometrial petechiae (chi(2) = 37.9, P0.0001) and ecchymoses (chi(2) = 42.2, P = 0.0001) were more frequently observed in the Norplant users than in the menorrhagia group. In Norplant users, superficial endometrial vascular fragility was increased in those with frequent bleeding or spotting during the past 30 days (chi(2) = 6.15, P = 0.01), and in those who were examined during a bleeding episode (chi(2) = 5.3, P = 0.02). Fragility was increased in the menorrhagia group during the perimenstrual period (days 24 to 05; chi(2) = 12.83, P = 0.01). There was no obvious relationship between subepithelial bleeding and circulating concentrations of oestradiol and progesterone.

Progestogen-only contraception is almost invariably associated with changes in menstrual bleeding patterns. Changes in the endometrial vasculature, and in particular an increase in vascular fragility, may contribute to this bleeding. In this study, endometrial vascular density and endothelial cell basement membrane components were examined using immunohistochemistry before and after insertion of Norplant. Endometrial vascular density was increased from a mean (+/- SEM) of 189.6 +/- 7.0 vessels/mm2 during the control cycle to 253.9 +/- 80.7 vessels/mm2 at 2-13 weeks of Norplant exposure, and to 212.7 +/- 12.9 vessels/mm2 at 14-42 weeks. During the control cycle, a mean of 161.4 +/- 4.5 vessels/mm2 stained for collagen IV (85% of all vessels), while at 2-13 weeks, 144.5 +/- 13.0 vessels/mm2 stained for collagen IV (57% of all vessels) (t ratio = 2.08, P = 0.0057). By 14-42 weeks, 71% of vessels (151.0 +/- 9.8) vessels/mm2 were surrounded by collagen IV. This was not significantly different from control values (t ratio = 2.03). Endometrial vascular laminin was also reduced following Norplant insertion, from a mean of 176.0 +/- 4.2 vessels/mm2 in the control cycle (93% of vessels), to 156.3 +/- 6.7 vessels/mm2 at 2-13 weeks of exposure (57% of vessels) (t ratio = 2.08, P = 0.01). By 14-42 weeks of exposure to Norplant, 162.5 +/- 9 vessels/mm2 (76%) stained for laminin. This was not significantly different from control values (t ratio = 2.04). Endometrial vascular heparan sulphate proteoglycan (HSPG) was reduced from 58.6 +/- 3.0 vessels/mm2 during the control cycle (31% of vessels) to 43.6 +/- 5.6 vessels/mm2 (only 17% of vessels) at 2-13 weeks (t ratio = 2.08, P = 0.025). At 14-42 weeks, only 19% of vessels stained for HSPG (41.3 +/- 5.8 vessels/mm2; t ratio = 2.04, P = 0.009).

Depot medroxyprogesterone acetate (DMPA) was the first popular long-acting progestogen-only contraceptive, and is used by more than nine million women worldwide. It is one of the most convenient and effective, yet readily reversible methods of contraception. Although application was first submitted to the US Food and Drug Administration in 1967 for approval to market DMPA as a contraceptive, final approval only came years later in late 1992. DMPA is now approved for marketing as a contraceptive in more than 100 countries, mainly as Depo-Provera for intramuscular use in a 150 mg dose, although several generic products are available in many countries. Many clinicians have access to DMPA as a contraceptive for the first time, and most are aware of the substantial controversy surrounding its use. This paper discusses the role of DMPA in the current array of contraceptive choices, offering guidance for the common clinical problems which may present with use. Sections cover dosage, administration, and contraceptive action; advantages and disadvantages of DMPA; controversies and DMPA; acceptability; and indications and contraindications for use

A 32-year-old woman presented with a five-year history of primary infertility. In addition to anovulation associated with hyperprolactinaemia, she was found to have high titres of anti-sperm antibodies of agllutinating and immobilizing types. These were present in both serum and cervical mucus. After the regular use of condoms for nine months, all antibody titres fell dramatically and immobilizing antibodies became undetectable. Successful pregnancy quickly ensued. This report documents in thorough detail for the first time the sequential antibody changes associated with successful occlusion therapy.

Four women out of 242 experienced amenorrhoea in excess of 6 months duration following danazol treatment. Two of these exhibited an unusual monotropic rise of FSH into the post menopausal range for 4-5 months following the end of therapy. This was associated with an excessive response to GnRH injection. The mechanism of this temporary FSH rise is unknown. A causal association of the amenorrhoea and monotropic FSH rise following danazol therapy is unproven but seems likely.

We describe a problem in measuring serum testosterone concentrations in the serum of women who are taking danazol. The Diagnostic Products Corporation testosterone radioimmunoassay gives very high apparent testosterone concentrations in these women and the value obtained depends on the volume of serum extracted per assay tube. Chromatography of the serum extracts on Sephadex LH-20, but not on Celite, before radioimmunoassay reduced these high apparent testosterone concentrations to less than that found in normal women.

Platelet count and platelet function have been studied in detail in 14 women before and during treatment with danazol for endometriosis. A progressive and highly significant increase in platelet count was recorded from the pretreatment value (311 x 10(9)/L) to the value after six months of treatment (366 x 10(9)/L; P less than 0.001). Five patients developed minor platelet release defects, which may have been caused by the drug. However, the abnormalities shown are only likely to be of clinical importance in patients with preexisting platelet abnormalities.