Nonsteroidal anti-inflammatory drugs and changing attitudes toward dysmenorrhea.

Dysmenorrhea, which may be primary or secondary, is the occurrence of painful uterine cramps during menstruation. Until a decade ago, medical and social attitudes toward dysmenorrhea were shrouded with folklore, psychoanalytical profiles, or psychosomatic bases. In secondary dysmenorrhea, there is a visible pelvic lesion to account for the pain, whereas only a biochemical abnormality is responsible for primary dysmenorrhea. Recent advances in the biochemistry of prostaglandins and their role in the pathophysiology of primary dysmenorrhea and intrauterine device (IUD)-induced dysmenorrhea have now firmly established a rational basis for the disorder. In primary dysmenorrhea, menstrual prostaglandin release is significantly increased but can be readily suppressed to normal levels when nonsteroidal anti-inflammatory drugs (NSAIDs) capable of inhibiting cyclo-oxygenase are given during menstruation. Many clinical trials (controlled and uncontrolled) have demonstrated the efficacy of NSAIDs such as the fenamates, indole-acetic acid derivatives, and arylpropionic acid derivatives in relieving primary dysmenorrhea as well as IUD-induced dysmenorrhea that is also due to elevated prostaglandin levels. With a few of these NSAIDs, it has been shown that the relief of pain is associated with a significant decrease in menstrual fluid prostaglandin levels. Cumulative data of clinical trials indicate that with the effective NSAIDs, 80 percent of patients with significant primary dysmenorrhea can be adequately relieved. Ongoing studies suggest that in some women, endometrial leukotriene, but not PGF2a production, is increased. With the official approval and availability of several effective NSAIDs for the specific treatment of primary dysmenorrhea in the United States, women who have primary dysmenorrhea have been greatly relieved and their productivity increased. Primary dysmenorrhea affects 50 percent of postpubescent women and absenteeism among the severe dysmenorrheics has been estimated to cause about 600 million lost working hours or 2 billion dollars annually. Thus, an effective, simple, and safe treatment of primary dysmenorrhea for two to three days during menstruation will not only have a positive economic impact but will also enhance the quality of life. The availability of effective dysmenorrhea therapy with NSAIDs has induced greater expectations of relief by the patient, as well as greater willingness to seek medical help, a more rational approach to patient management by physicians, changes in attitude toward women with primary dysmenorrhea, and the debunking of myths about dysmenorrhea that often have been perpetuated as fact.(ABSTRACT TRUNCATED AT 400 WORDS)

PIP: The availability of effective dysmenorrhea therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) has been accompanied by greater expectations of relief on the part of the patient, increased willingness to seek medical help, a more rational approach to patient management by physicians, changes in attitude toward women with primary dysmenorrhea, and a debunking of the myths associated with dysmenorrhea. Following a review of the prevalence, social and economic impact, and the nonmedical myths surrounding dysmenorrhea, attention focuses on the cause and clinical diagnosis of dysmenorrhea and the therapeutic use of NSAIDS. NSAIDs Relief can be obtained in 80-85% of patients studied, with NSAIDs shown to be clinically effective against primary dysmenorrhea. Several NSAIDs have been shown to relieve primary dysmenorrhea through the suppression of menstrual fluid prostaglandins. Primary dysmenorrhea now is more often diagnosed on the basis of its positive features rather than by the exclusion of other disorders as was previously the case. As yet, it is unclear as to why 15-20% of patients fail to have an adequate response to NSAIDs. As patients can obtain effective relief from primary dysmenorrhea from treatment with the appropriate NSAID, there is a significant impact on work productivity, absenteeism, economic loss, social adjustment, and patient attitude toward menstruation and medical help.

IUDs, inflammation, and infection: assessment after two decades of IUD use.

PIP: In the 1950s social and technological changes allowed experimental use of an inert plastic IUD which was successful and regarded as safe. The devices were pliable, chemically inert, sterilizable, disposable, and equipped with a small inserter so that cervical dilation was not needed for insertion. But many IUDs were withdrawn because they were found to cause endometritis and provide poor protection against pregnancy. In the 1970s there were cases of serious inflammatory and infectious diseases with pelvic inflammatory disease (PID) the most common. The Dalkon Shield has been associated with midtrimester septic abortions and with unilateral actinomycotic tube-ovarian abscesses and there is evidence to support a chemically caused IUD-related endometritis in the moderate inflammation associated with IUDs containing copper and with the Majzlin spring. The most common factor among IUD users with Actinomycetales infection is not the type of IUD but the duration of use; almost 85% of cases were in women who had worn IUDs over 3 years. Also the likelihood of an ectopic pregnancy is almost 3 times greater for longterm IUD users. It is hypothesized that with time the IUD is capable of inducing changes that can lead to infection and that changes can occur to the IUD itself. A surface coating on the IUD and the tail has been found which is composed of mucoid and cellular elements which consist of an inflammatory response; the IUD then becomes recognized as a foreign body to the host and may contribute to the development of PID. Other problems such as perforation, cramping, bleeding, and unwanted pregnancy may be at least indirectly related to IUD surface alterations. It is now agreed that all IUD-associated inflammatory and infectious disease can no longer be considered gonorrheal type PID and that the biodegradation of the nylon-6 tail of the Dalkon shield may also be a factor in PID. Some recommendations are to: 1) change IUDs every 2 years, 2) counsel women on IUD complications and examine IUDs upon removal, and 3) bring IUD technology up to date to develop an IUD that is thoroughly safe and effective.^ieng

Scanning electron microscopy, x-ray diffraction, and electron microprobe analysis of calcific deposits on intrauterine contraceptive devices.

Deposits found intrauterine contraceptive devices (IUDs) were studied by scanning electron microscopy, x-ray diffraction, and energy dispersive x-ray microanalysis. All seven devices, including five plastic and two copper IUDs, were coated with a crust containing cellular, acellular, and fibrillar material. The cellular material was composed of erythrocytes, leukocytes, cells of epithelial origin, sperm, and bacteria. Some of the bacteria were filamentous, with acute-angle branching. The fibrillar material appeared to be fibrin. Most of the acellular material was amorphous; calcite was identified by x-ray diffraction, and x-ray microanalysis showed only calcium. Some of the acellular material, particularly that on the IUD side of the crust, was organized in spherulitic crystals and was identified as calcium phosphate by x-ray microanalysis. The crust was joined to the IUD surface by a layer of fibrillar and amorphous material. It is suggested that the initial event in the formation of calcific deposits on IUD surfaces is the deposition of an amorphous and fibrillar layer. Various types of cells present in the endometrial environment adhere to this layer and then calcify. Thus, the deposition of calcific material on the IUDs is a calcification phenomenon, not unlike the formation of plaque on teeth. Hum Pathol 16:732-738, 1985.

Intrauterine device use and endometrial cancer risk.

BACKGROUND: Because intrauterine devices (IUD) invoke acute and chronic inflammatory responses in the endometrium, it is possible that prolonged insertion of an IUD could induce endometrial cancer. METHODS: We examined the relation between use of an IUD and endometrial cancer risk using data from a multicentre case-control study involving 405 endometrial cancer cases and 297 population controls. RESULTS: A total of 20 (4.9%) cases and 34 (11.4%) controls reported any use of an IUD. After adjustment for potential confounders, IUD use was not associated with an increased risk of endometrial cancer (RR = 0.56 for ever use; 95% CI: 0.3-1.0). Little reduction in risk was observed among women who last used an IUD within 10 years of the index date (RR = 0.84; 95% CI: 0.3-2.4) but risk was decreased among women who used an IUD in the more distant past (RR = 0.45; 95% CI: 0.2-1.0). Risk did not vary consistently with number of years of IUD use or with years since first use. Risk was not increased among women who used inert devices (RR = 0.46; 95% CI: 0.3-3.6) or those who used devices containing copper (RR = 1.08; 95% CI: 0.1-3.6). CONCLUSION: These data are reassuring in that they do not provide any evidence of an increased risk of endometrial cancer among women who have used IUD.

PIP: IUDs invoke acute and chronic inflammatory responses in the endometrium. The authors therefore explored whether the prolonged insertion of an IUD increases one's risk of developing endometrial cancer. The relation between the use of an IUD and endometrial cancer risk was examined using data from a multicenter case-control study involving 405 endometrial cancer cases and 297 population controls. 20 cases and 34 controls reported using an IUD. After adjusting for potential confounders, IUD use was not associated with an increased risk of endometrial cancer. A small reduction in risk was observed among women who last used an IUD within 10 years of the index date, with the risk further reduced among women who last used an IUD more than 10 years ago. Risk did not vary consistently with the number of years of IUD use or with years since first use. Furthermore, the level of risk was not increased among women who used inert devices or those who used copper-containing devices.

Actinomyces odontolyticus isolated from the female genital tract.

Actinomyces odontolyticus was isolated from genital tract specimens from 4.8% of 561 women fitted with intrauterine contraceptive devices and from 4% of 101 women with pelvic inflammatory disease and 1.8% of 525 women without pelvic inflammatory disease who were not known to be intrauterine contraceptive device wearers. The strains were isolated by prolonged anaerobic incubation of blood agar, with or without added 5% metronidazole or 1% neomycin. A odontolyticus has not been previously reported in cervico-vaginal specimens, and possible reasons for this are discussed.

Intrauterine contraception in adolescent women. The GyneFix intrauterine implant.

Pregnancy rates among adolescents have not decreased over the last 10 years, despite numerous efforts. To solve this important health problem, the major strategy recommended is to encourage contraceptive use among sexually active teenagers. An important means of obtaining this is by promoting methods that are not dependent on daily administration in order to avoid noncompliance. One such method (Norplant) has already shown to be much more effective than the combination pill in preventing pregnancy in adolescent women. The frameless intrauterine implant system (fixed, frameless, and completely flexible) has been studied since 1985 in women between 14 and 50 years of age. The results in young nulligravid women confirm its very high effectiveness (cumulative pregnancy rate at 36 months: 1.4%), its low expulsion rate (cumulative rate at 36 months: 0.9%) and its optimal tolerance (cumulative removal rate for medical reasons at 36 months: 2.4%), resulting in a high acceptance of the implant and a high continued use. The system (GyneFix) offers long-term protection (5 years), and its insertion, with or without anesthetic, is easily accomplished in the office. The GyneFix should therefore be recommended as an excellent alternative for birth control pills for young women with low risk for STDs, especially when compliance is a problem, without an increased risk for complications and without systemic side effects. Removal of the device is accomplished by traction on the tail. It can also be used for emergency contraception and for insertion immediately after termination of pregnancy.

Dislocated IUD and intrauterine ectopic pregnancy with uterine rupture.

A case of uterine rupture due to an ectopic pregnancy in the uterine fundus is presented. A Lippes Loop was found rotated in the uterine cavity. A possible relation between implantation and the dislocated intrauterine device is proposed.

PIP: A case report of uterine rupture due to an ectopic pregnancy in the uterine fundus in a 33-year-old women, gravida 4, para 3, inserted with a Lippes loop C in 1969 is presented. A pregnancy was diagnosed early in 1973 and the patient admitted for laparotomy with a preoperative diagnosis of left extrauterine pregnancy. The uterus was enlarged and the fundus was protrusive with a bleeding rupture unassociated with the tubes which were normal. Supravaginal hysterectomy was performed. In the fundus a large hematoma was found which was partly embedded in the uterine wall and had ruptured the serosa. A Lippes loop was found rotated 180 degrees in the uterine cavity. Microscopic examination of the hematoma revealed fetal material. A possible relation between implantation and the dislocated IUD is proposed.

Progesterone and estradiol patterns in women using an intrauterine contraceptive device.

Levels of progesterone, estradiol, LH, and FSH were measured in daily serum samples obtained from 4 subjects during a control cycle and during the first and fourth menstrual cycles after insertion of an intrauterine device (IUD). In addition, progesterone and estradiol were measured in serum samples obtained from 6 women 3, 4, or 5 months after IUD insertion, and from 6 women more than 1 year after IUD insertion. These measurements were compared to the data obtained from study of a large group of normal cycles. The results indicated that the IUD does not influence follicular maturation, time of ovulation, or corpus luteum function. The IUD did exert a local effect on the endometrium, causing the onset of menses to take place when steroid levels were higher than in control cycles.

PIP: In an attempt to resolve differing results on the effect of the IUD on steroid and gonadotropic levels in women wearing the IUD, levels of progesterone, estradiol, luteinizing hormone, and follicle stimulating hormone were measured in daily serum samples obtained from 4 subjects during a control cycle and during the 1st and 4th menstrual cycles after insertion of an IUD (Lippes loop D or TCu 200). Progesterone and estradiol were measured in serum samples obtained from 6 other women 3, 4, or 5 months after IUD insertion (Copper T) and from these another group of 6 women 1 year or more after insertion. These measurements were compared to data obtained from study of a large group of normal cycles. The results indicated that influence on follicular maturation, time of ovulation, or corpus luteum function by an IUD is absent. The IUD exerted a local effect on the endometrium, causing the onset of the menses to take place when steroid levels were higher than in control cycles.

Cholesterol content of menstrual discharge. Influence of contraceptives.

PIP: An investigation was undertaken to study the cholesterol content of menstrual discharge and to establish its relationship to the cyclic acti vities of the endometrium. The effects that an oral contraceptive and IUD might have on cholesterol concentration in menstrual discharge and blood serum were also investigated. A total of 38 subjects were used. 9 were taking the oral contraceptive, Ortho-Novum; 4 were fitted with an IUD; and the remaining 25 were used as controls. Blood and menstrual discharges were collected and tested. Blood serum levels for all groups were constant during the menstrual cycle. It was found that the concentrations of cholesterol in the menstrual discharge samples of each group were significantly lower than the corresponding values in blood serum. The cholesterol levels in the menstrual discharge of the control and IUD groups were in the same narrow range and did not vary with the day of the cycle. The values for the oral contraceptives users also did not vary significantly with the day of the cycle, but they were signific antly lower than for levels obtained for the other 2 groups. The total excretion rate of cholesterol was highest for the IUD group, while the oral contraceptive users showed a significantly lowered rate of excretion than either the control or IUD group. The high excretion pattern shown by the IUD group is a reflection of these women's heavier flow.^ieng

A risk-benefit assessment of the levonorgestrel-releasing intrauterine system.

The levonorgestrel-releasing intrauterine system (LNG-IUS), has been developed by Leiras Pharmaceuticals, Turku, Finland. It is a new systemic hormonal contraceptive that releases levonorgestrel 20 micrograms every 24 hours. The device provides fertility control comparable with that of female sterilisation, complete reversibility and convenience, and has an excellent tolerability record. The low dosage of levonorgestrel released by its unique delivery system ensures minimal hormone-related systemic adverse effects, which tend to be in the category of 'nuisance' rather than hazardous, and gradually diminish after the first few months of use. In some respects, the contraceptive characteristics of the LNG-IUS have over-shadowed a substantial range of noncontraceptive beneficial effects that are rarely seen with inert or copper-releasing intrauterine contraceptive devices (IUDs), and have important and positive gynaecological and public health implications. This applies particularly to the profound reduction in duration and quantity of menstrual bleeding, and alleviation of dysmenorrhoea, which are associated with the use of the device. Recent studies have shown that the LNG-IUS is effective in preventing endometrial proliferation associated with oral or transdermal estradiol therapy, and in inducing regression of endometrial hyperplasia. Further research is required to determine whether it has a role in regulating the growth of uterine fibroids, and preventing pelvic inflammatory disease. The unique unwanted noncontraceptive effects of the system, including possible development of functional ovarian cysts, and the relationship between menstrual bleeding pattern and ovarian function, also require better understanding, in order to offer appropriate patient counselling and maximise acceptability and continuation of use of the method.

PIP: The levonorgestrel-releasing intrauterine system (LNG-IUS) provides fertility control comparable to female sterilization, convenience, and complete reversibility. This method appears to combine the benefits of oral contraception and the IUD, while avoiding most of their side effects. The low level of LNG released (20 mcg every 24 hours) minimizes the systemic adverse effects associated with hormonal contraception. Unlike inert or copper IUDs, the LNG-IUS is associated with a profound reduction in the duration and quantity of menstrual bleeding and alleviates dysmenorrhea. Moreover, there is evidence that the LNG-IUS prevents the endometrial proliferation associated with estradiol therapy and induces regression of endometrial hyperplasia; its potential for regulating the growth of uterine fibroids and preventing pelvic inflammatory disease remains undetermined. Although large multicenter studies have not detected differences in cervical cytology or breast cancer incidence between copper IUD and LNG-IUS users, long-term epidemiological studies are needed to confirm this finding. Fundal positioning of the LNG-IUS is essential to ensure uniform exposure of the endometrium to the progestogen, prevent expulsion, and maximize efficacy. A promising future use for the LNG-IUS is in protecting the endometrium during postmenopausal hormone replacement therapy. Overall, the research suggests that the LNG-IUS comes close to meeting many of the requirements of an ideal contraceptive.

The effect of a copper intra-uterine contraceptive device on the microbial ecology of the female genital tract.

Bacteria isolated from 108 intra-uterine contraceptive devices (IUCD) removed from patients with pelvic inflammatory disease (PID), haemorrhage, pregnancy and from asymptomatic women, and from the genital tracts of 66 healthy controls not wearing an IUCD, were studied. No significant differences were found in the types of micro-organisms or isolation rates from IUCDs removed from women in the various clinical groups. The isolation rate of anaerobic bacteria from IUCDs removed from asymptomatic wearers was significantly lower than that from controls, with the exception of the isolation rate of actinomyces which was significantly higher in IUCD wearers and A. israelii was recovered only from IUCDs. The isolation rates of the different bacterial species varied with the duration of the device in utero. The presence of a copper IUCD altered the bacterial flora of the female genital tract. The insertion of such a device and the ecological changes that follow play a crucial role in the development of PID.

PIP: The bacterial flora of the cervix and vagina were examined in 108 patients who had copper IUDs removed and in 66 controls at the Maternity Hospital and Maternal Welfare Clinics in Kuwait. The IUDs removed were the Nova-T, Copper 7, and Cu 250. 15 of the women having IUDs removed had pelvic inflammatory disease; 21 had irregular bleeding; 11 had suprapubic pain, vaginal discharge, or uterine perforation; and 51 were asymptomatic. Actinomyces species, particularly Actinomyces israelii, and Arachnia propionica were isolated from 16 of the IUD wearers but only 2 of the controls. Lactobacillus species were isolated from 10 of the IUD wearers and 25 of the controls. Anaerobic cocci were isolated from 13 device wearers and 12 controls. Except for Actinomyces, anaerobic bacteria were isolated from controls more often than from the IUD wearers. Copper is known to have an antibacterial effect on gram-positive anaerobes, and even Actinomyces was absent from IUD wearers who had worn the device less than a year, i.e., during the period of maximum copper release. Moreover, no significant difference was found in the patients in the different clinical groups. The presence of an IUD does promote colonization of the genital tract by Actinomyces. However, other factors must be considered in the development of pelvic inflammatory disease. The creation of an acidic environment by some bacteria, such as Lactobacillus, may promote the growth of some pathogens, while inhibiting the growth of others. Furthermore, the insertion of an IUD breaches the protective barrier of the cervical mucus, and the IUD tail creates a transmission link into the uterus.

Effects of contraceptive pills and intrauterine devices on urinary bladder.

The incidence of bacteriuria and cystoscopic changes in women on oral contraceptives or users of IUD (intrauterine devices) were evaluated compared with a control group. Subjects with bacteriuria accounted for 40.5 per cent of pill users, 20 per cent of women fitted with IUD, and 16 per cent of the control group. Bladder trabeculations were found in 50.5 per cent of the pill group, 8.7 per cent of the IUD group, and 8 per cent of the controls. Congested bladder trigone was observed in 24.6 per cent of women fitted with an IUD. The mode of action of ovarian hormones and their possible side effects on the bladder are discussed. The relation of IUD to pelvic inflammatory disease and its effect on the urinary bladder are evaluated.

PIP: The incidence of bacteriuria and cystoscopic changes in 200 women using oral contraceptives from 1 month to 2 years and 150 users of IUD were compared with 50 women using neither method. Bacteriuria in midstrean urine samples of all subjects were identified qualitatively and quantitatively by the method of Stamey et al. Cystoscopy was performed on all subjects. Positive bacteriuria were found in 40.5% of patients on oral contraceptives, 20% of IUD users, and 16% of the control group. Positive pathogenic bacterial cultures in women using oral contraceptives were proportional to the length of time the pill had been used: 27% for 1 year users, 35% for 2 year users, and 50% for longer users. The potency and dosage is correlated with the pathogenic effects observed. Bladder trabeculations were found in 50.5% of oral contraceptive users, 8.7% of IUD users, and 8% of control subjects. The highest incidence was in subjects using pills for 2 years or more, and is correlated with the dosage used. Bladder trigone congestion was observed in 24.6% of IUD users; 56% of users from 1 to 3 months, 35% of users more than 2 years, and no users between these time extremes. The high incidence of bladder trabeculations might be explained by the effect of progestogens and estrogens on bladder tone; progestogens producing hypotonia and estrogens hypertonia. The IUD should not be used more than 2-3 years continuously to avoid urinary bladder effects and inflammatory pelvic disease.

The effect of intrauterine contraceptive device (IUD) on pregnancy in the rabbit.

PIP: Rabbits were inserted with 10 cm of Silastic tubing in 1 uterine horn; blastocysts were collected from the control or treated horn on Pregnancy Day 5 and transferred to the opposite horn. 16 of 22 (72%) blastocysts implanted into an IUD horn failed to survive to Day 23. 10 of 16 (62.5%) blastocysts transferred to the control horn were found implanted on Day 12 and 9 pups were delivered. In other rabbits with su rgical anastomosis between the 2 horns, 99.5% of implantations survived from Day 12 to 23 in control horns, but only 20% in IUD horns. The leukocyte counts was markedly elevated in IUD horns and only moderately in control horns. These data indicate that the antifertility effect of the IUD is largely due to its direct contact with the developing embryos and the endometrium.^ieng

A simple technic of hysterography for evaluating side effects and mode of action of intrauterine devices. A study of 100 cases.

PIP: This paper describes the use of a simple technique of hysterography to evaluate the side effects and mode of action of IUD. The technic utilizes 2 x-ray films per patient of the lower abdomen: a flat film to determine the presence or absence of the device, and a hysterogram; diluted water-soluble contrast medium was used, allowing visualization of the device and the endometrial cavity in a single x-ray exploration. The technic was performed on 100 women fitted with Lippes loop; 74 of these experienced side effects while 22 patients with no complaints were used as controls; 1 had an asymptomatic uterine peforation with the loop lying in the pelvis and 3 were pregnant (2 had a double uterus). In the control group, the hysterograms were performed 3-6 months after loop insertion while in the study group, the hysterogram were done 3-190 days after insertion, with the exception of true expulsion cases where a device similar to that ejected was reinserted just before taking x-ray. 44 patients were found to have bilateral cornual spasm. Incomplete fundal coverage of the device was associated with an increase in the incidence of side effects, mainly bleeding. Out of 23 cases of clinically suspected expulsion, the device was found in situ in 12 cases. In 10 cases, the IUD position was reversed with the thread withdrawn into the uterine cavity. In the remaining 2, the loop was found in the abdominal cavity. Congenital uterine abnormality was also found in 4 out of 10 cases with true expulsion. The incidence of side effects can be minimized by constructing IUDs which would fit properly into the endometrial cavity. Hysterography is a useful diagnostic tool for determining the incidence of side effects and possible mode of action of IUDs; it can also provide an index of the probable efficiency of the device after insertion.^ieng

Microbial presence in the uterine cavity as affected by varieties of intrauterine contraceptive devices.

A group of 33 baboons was used to study the effect of various intrauterine device (IUD) assemblies on the entrance of vaginal/cervical microflora into the uterine cavity for a total experimental period of 16 months. These animals were specially prepared surgically so that intrauterine samples could be taken aseptically and percutaneously rather than transvaginally. While the insertion and presence of any of the IUD assemblies used in this study could promote intrauterine bacteria, the principal determining factor was not the device itself, but rather retrieval tail. Multifilament tails were much more effective than monofilaments. Of particular interest is the fact that many potential pathogens can be present in the uterus for long periods in a benign, almost "normal flora" fashion without producing disease.

The effect of intrauterine devices containing zinc and copper on their levels in serum.

Serum levels of copper and zinc were determined in 11 health women in whom Latex Leaf intrauterine devices (IUDs) containing copper and zinc had been inserted. Patients with low levels of serum copper or zinc before insertion usually had increased levels of either of these metals while using the device, but they did not exceed the upper limits of normal values. When the group was considered as a whole, the serum levels of zinc showed a slight tendency to increase with duration of IUD use, whereas there was no statistical difference between the serum levels of copper before and after insertion of the IUD.

PIP: Serum levels of copper and zinc were measured in 111 healthy women in whom Latex Leaf IUDs containing copper and zinc had been inserted. The women ranged from 21 to 41 years of age. Months of use ranged from 1 to 23 with an average of 14.6. The 1st blood sample was obtained before insertion and the 2nd from 1 to 19 months after insertion. Mean level of serum copper in the 1st sample was 1.42 mcg/ml. Age and parity had no effect; a slight tendency for higher levels was observed only in multigravidas. There were no significant changes in mean copper levels even when the levels were correlated with duration of usage. Mean serum zinc level before insertion was 1.1 mcg/ml with no correlation to age, gravidity, or parity. The 2nd sample showed a slight increase, 109% + or -3.25% standard error p .005. This increase correlated with the time the device was in situ. In general, patients with low levels of serum copper or zinc before insertion usually had increased levels after use but these levels did not exceed the upper limits of normal values. This may be due to an initially low level of the copper fraction bound to serum albumin and indicates the existence of some equilibrium between free and bound metal in the system.

Pelvic inflammatory disease with intrauterine device use: a reassessment.

This reassessment of IUDs as a risk factor for PID contrasts study results from prospective and case-control studies. Except for a transient increased risk after IUD insertions, increased risk is seen mainly in case-control studies after 1973, the time of a major PID epidemic and adverse publicity related to the Dalkon Shield. Removal of oral contraceptive users from case-control studies generally reduces their reported odds ratios, frequently to borderline statistical significance for studies with high accuracy of PID diagnosis. The remaining elevated odds ratios likely relate to diagnostic bias as primary care clinicians are more likely to refer patients wearing an IUD to referral centers where case-control studies are conducted. Biased case-control studies provided evidence for expensive litigation, resulting in removal of IUDs from the American market. The Food and Drug Administration requirements for postmarketing surveillance are inadequate to provide prospective data to avoid this kind of loss.

PIP: A reassessment of the relation between IUD use and pelvic inflammatory disease (PID) suggests that the correlation may not be supported by prospective cohort studies. The increased risk of pelvic inflammatory disease associated with IUD use was based primarily on case control studies after 1973, at which time there was a major PID epidemic and adverse publicity about the Dalkon Shield. Because case control studies may have been biased, these studies should not form the basis for the current consensus that IUD use increases the risk of PID. Problems with case-control studies include inaccuracy of PID diagnosis, the removal of oral contraceptive users from such studies, and miscalculations about the relative risk of PID. Another important factor is the increased incidence of sexually transmitted disease. These factors contributed to the current teaching in medical schools that IUD use increases the risk of PID. Although there is a small increased risk of PID in IUD users, due primarily to contamination of the uterine cavity during insertion, the risk is low. A comparison of case-control studies with prospective cohort studies does not support the association between IUD use and PID, and this should be considered when recommendations are made to physicians from developing countries. The potential of such instruction in influencing family planning policy decisions could have serious consequences for developing countries.

Contraception and cervical colonization with mycoplasmas and infection with cytomegalovirus.

The relationship of cervical colonization of genital mycoplasmas and infection with cytomegalovirus (CMV) was studied in 66 intrauterine device (IUD) users as contrasted to 60 patients using oral contraception and 50 patients using neither an IUD nor oral contraception. No significant increase in colonization or genital mycoplasmas or infection with CMV was noted in IUD users. No CMV was isolated from users of the cooper-t IUD. It is unlikely that genital mycoplasmas are related to either the increased immunoglobulin levels seen in patients using the IUD or the antifertility effects of the IUD.

PIP: An ivestigation based on the hypothesis that the IUD might induce an endometritis related to a nonbacterial infection was undertaken in 66 IUD users and contrasted to 60 oral contraceptive (OC) users and 50 nonusers of OCs and IUDs. The relationship of cervical colonization of genital mycoplasmas and infection with cytomegalovirus (CMV) was studied yielding the following information: 1) Genital mycoplasma colonization among the groups studied differed insignificantly; 2) An insignificant increase in colonization of genital mycoplasmas or infection with CMV was noted in IUD users; 3) There were no CMV isolates from the group using the Copper T IUD; 4) CMV infection did not appear to be significantly increased by IUD presence; and 5) The overall rate of 5.2% of CMV infection was comparable with that of other studies. Results indicated the unlikelyhood that genital mycoplasmas are related to either the increased immunoglobulin levels noted in patients using the IUD or to the IUD's antifertility effects.

Hemorrhage induced by intrauterine devices: control by local proteinase inhibition.

The intrauterine application of proteinase inhibitors, tranexaminc acid and the pancreatic trypsin inhibitor (Trasylol), reduces or eliminates menorrhagia and intermenstrual bleeding (spotting) produced by an intrauterine device (IUD). A decrease in pain and vaginal (cervical) discharge is also frequently observed. A single application is usually sufficient, more than three never being required. The effect lasts for an average of three cycles. In addition to the clinical use of these agents for the treatment of uterine hemorrhage, the slow release of proteinase inhibitors from an IUD may well be useful in minimizing its side effects without interfering with its contraceptive activity.

PIP: 2 fibrinolytic inhibitors were evaluated in IUD-wearing women complaining of menorrhagia and spotting to determine if direct application into the uterus could reduce such side effects of IUD wear. The agents used were the proteinase inhibitor transexamic acid (AMCA) and a naturally occurring pancreatic trypsin inhibitor Trasylol. Solutions of the antifibrinolytic agents (1 gm/ml AMCA and 19 gm/ml Trasylol) were injected into th eue rine cavity. 10 of the women acted as control. Both agents reduce the length of the menstrual period by about 50% with a significant reduction in pain and vaginal discharge. This effect was usually sustained over several menstrual cycles. Local administration is more advantageous than the oral approach because smaller dosage is required and side effects thus reduced. It is suggested that proteinase inhibitors be incorporated directly into IUDs.

Dimensional and architectural disproportion between the intrauterine device and the uterine cavity. A casue of bleeding.

PIP: Hysterograms were performed on 172 women fitted with 30 mm Lippes Loops to determine uterine dimensions. Uteri classifications were: normal; triangular, divided into 1) small triangle, 30 mm. loop was too large; 2) medium triangle, device fits snugly, less severe bleeding at 7 months; 3) large triangle, device too small, mild bleeding at 10 months and formal conical cavity, divided into 1) narrow fundus, too small for device, leading to traumatic bleeding; 2) medium, device fits snugly causes intermenstrual bleeding; 3) large, loop covers only a portion of uterine cavity, bleeding less severe later. Ideally the IUD should fit snugly against the various borders of the uterine cavity, exerting light and equal pressure. Congenital anomalies and devices incorrectly positioned caused intermenstrual bleeding.^ieng