Etiology of cancer of the human ovary: a review.

PIP: A review of factors known or suspected of causing cancers of the human ovary revealed little specific information. The worldwide distribution of ovarian cancer, similar to that of other prevalent cancers, suggests associations with environmental carcinogens. However, few clues exist as to which suspected chemical or physical agents are actually involved. Those factors which point to a high risk for ovarian cancer have not yet been identified except for the greater risk which exists for nulliparous women, those women with breast carcinoma, and those members of the rare "ovary cancer families." Despite epidemiologic associations of cancers of the ovary and breast, a 1st pregnancy at a young age has not been shown to decrease the risk for cancer of the ovary as with cancer of the breast. Experiments testing effects of suspected ovarian carcinogens have been difficult to interpret because ovarian neoplasms induced in rodents by irradiation and chemical carcinogens are of histologic types that are either infrequent, do not occur in human ovaries, or do not metastasize. Only chickens develop significant numbers of ovarian adenocarcinomas similar in histologic appearance and behavior to the common human epithelial carcinomas, but these have not been adequately investigated.^ieng

Effects of the antiprogesterone steroid RU 486 during midluteal phase in normal women.

UNLABELLED: The antiprogesterone steroid RU 486 (17 beta-hydroxy-11 beta-4-dimethyl-aminophenyl)17 alpha(1-propynyl)estra-4,9-dien-3-one) was given orally to 32 normally cycling women for 4 days, starting on the fourth day of the luteal phase. Uterine bleeding occurred on the third day of RU 486 administration in all 14 women treated with 100 mg/day, in 7 of the 8 women treated with 50 mg, and in 8 of 10 women receiving 25 mg/day. Premature luteal regression induced by RU 486 occurred in 8 women treated with 100 mg/day, in 3 treated with 50 mg, and in 2 receiving 25 mg/day. Plasma LH was measured every 15 min from 0800-1200 h for 5 days in 17 women. Mean LH levels decreased and pulsatile release disappeared in 7 of the 8 women treated with 100 mg, in 2 of 4 receiving 50 mg, and in 1 of 5 treated with 25 mg. RU 486 had no effect when given to 5 women with anovulatory cycles for 4 days starting on day 18 of the cycle. IN CONCLUSION: 1) RU 486, given to normally cycling women at midluteal phase, provokes uterine bleeding. 2) This effect occurs whether or not luteal regression is induced by the compound, indicating that RU 486 acts directly upon the endometrial tissue, very likely at the progesterone receptor level. 3) The drug may impair simultaneously or separately luteal function and gonadotropin secretion in a dose-dependent manner. 4) The lack of antiglucocorticosteroid activity, at the dosage of 100 mg/day, suggests that RU 486 may be useful for fertility control.

PIP: The antiprogesterone steroid RU 486 (17beta-hydroxy-11beta-4-dimethyl-aminophenyl)17alpha(1-propynyl)estra-4,9-dien-3-one) was given orally to 32 normally cycling women for 4 days, starting on the 4th day of the luteal phase. Uterine bleeding occurred on the 3rd day of RU 486 administration in all 14 women treated with 100 mg/day, in 7 of the 8 women treated with 50 mg and in 8 of 10 women receiving 25 mg/day. Premature luteal regression induced by RU 486 occurred in 8 women treated with 100 mg/day, in 3 treated with 50 mg, and in 2 receiving 25 mg/day. Plasma LH was measured every 15 minutes from 0800-1200 hours for 5 days in 17 women. Mean LH levels decreased and pulsatile release disappeared in 7 of 8 women treated with 100 mg, in 2 of 4 women receiving 50 mg, and in 1 of 5 treated with 25 mg. RU 486 had no effect when given to 5 women with anovulatory cycles for 4 days starting on day 18 of the cycle. The following were conclusions drawn. 1) RU 486, given to normally cycling women at midluteal phase, provokes uterine bleeding. 2) This effect occurs whether or not luteal regression is induced by the compound, indicating that RU 486 acts directly on the endometrial tissue, very likely at the progesterone receptor level. 3) The drug may impair simultaneously or separately luteal function and gonadotropin secretion in a dose-dependent manner. 4) The lack of antiglucocorticosteroid activity, at a dosage of 100 mg/day, suggests that RU 486 may be useful for fertility control.

Menstruation-related periodic hypersomnia: a case study with successful treatment.

A 16-year-old girl suffered from 1 to 2-week periods of hypersomnia associated with each menstruation. Serum hormone levels were normal. CSF concentrations of homovanillic acid and 5-hydroxyindolacetic acid were lower in hypersomniac than in symptom-free phases. 3-methoxy-4-hydroxyphenylethylene glycol was not affected. The sleep periods occurred only in connection with ovulatory menstrual cycles. When ovulation was inhibited by a combination of ethinylestradiol and lynestrenol, an oral contraceptive pill, the hypersomnia ceased. Thus, the hypersomnia seemed to be linked to the occurrence of ovulatory menstruations.

PIP: A 16-year old girl who had undergone normal pubertal development at 13 years 8 months began to menstruate with moderate or severe dysmenorrhea and 1 to 2 weeks of hypersomnia at 16 years 2 months. She was without symptoms between hypersomniac phases. The patient was followed for 3 years, in the hospital for 31 days and as an outpatient thereafter. Examination, including neurologic and gynecologic status, was normal. Serum levels of follicle stimulating hormone, luteinizing hormone, estradiol, and progesterone were normal. CSF concentrations of homovanillic acid and 5-hydroxyindolacetic acid were lower in her hypersomniac than in symptom-free phases. 3-methoxy-4-hydroxyphenylethylene glycol was not affected. The sleep periods occurred only in connection with ovulatory menstrual cycles. Inhibition of ovulation with the oral contraceptive pill Lyndiol, which contains a combination of 50 mcg ethinyl estradiol and 2.5 mg lynestrenol, led to a cessation of the hypersomnia. When treatment was discontinued, the patient had 2 cycles without ovulation and no sleep periods, but ovulation and periodic hypersomnia occurred regularly thereafter. Reinstitution of the contraceptive pill controlled the symptoms. Discontinuation of the treatment was tested 2 more times for 3 months each, and the ovulatory cycles were again accompanied by sleep periods.

Structure of a radiate pseudocolony associated with an intrauterine contraceptive device.

Transmission electron microscopy of a radiate pseudocolony associated with an intrauterine contraceptive device (IUCD) showed central bundles of extracellular fibers averaging 35 nm in diameter, surrounded by layered mantles of electron-dense, amorphous granular material. No bacterial, viral, or fungal structures were present. X-ray microanalysis revealed copper, sulfur, chloride, iron, and phosphorus; no calcium was found. It is postulated that these structures and histologically identical non-IUCD-associated granules from the female genital tract, as well as similar structures from other body locations, including those reported in colloid cysts of the third ventricle, are of lipofuscin origin.

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.

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.

Anovular corpus luteum in a woman taking an oral contraceptive.

PIP: When laparatomy was performed on 3 women treated with a combination-type oral contraceptive (5 mg lynestrenol, 150 MCG mestranol), an anovular corpus luteum was found in 1 ovary. Dating from the start of oral therapy, the times of the operations were Day 24, Cycle 1; Day 24, Cycle 2; and Day 23, Cycle 3 (anovular corpus luteum). The anovular corpus luteum was 6.5 mm long and 3.0 mm wide and had undergone considerable regression, about 3/4 of it having been converted into an avascular hyalinized mass. An unejected ovum, contour slightly altered and size approximately equal to that of ova in ovulation-ripe Graafian follicles, was situated in the center of the hyaline mass. The unejected ovum was the first one to be observed in a completely developed corpus luteum. The membrane pellucida was wider than usual, but the nucleus, nucleolus, and corona radiata cells surrounding the ovum had undergone little change. Hormone administration may have favorably influenced conditions of metabolism within the hyaline mass. Alterations in the anovular corpus luteum were compared with those found in the second treatment cycle in a corpus luteum formed during the first treatment cycle. The anovular corpus luteum was concluded to be the regressing corpus luteum of the first treatment cycle and approximately 65 days old.^ieng

Haemophilus influenzae in genitourinary tract infections.

Haemophilus influenzae was isolated in pure or predominant culture from genital specimens from nine females and two males. Four of the females had vaginitis, two had IUD-related endometritis, one had an incomplete septic abortion, and one had probable urethral syndrome. Two males had urethritis.

PIP: This report was prompted by the isolation of Haemophilus influenza from cultures of specimens from genital sites in 11 patients. All cervical, vaginal, and urethral specimens submitted to the Section of Clinical Microbiology Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, for bacterial culture are routinely inoculated onto blood agar, eosinmethylene blue (EMB) agar, chocolate blood agar, Columbia colistin-nalidixic acid (CNA) blood agar, and unless previously directly inoculated by the attending physician, modified Thayer-Martin medium. As a rule, identification and reporting of isolates is limited to Neisseria gonorrhoeae, N. meningitidis, Gardnerella vaginalis, beta-hemolytic streptococci, Listeria monocytogenes, and Staphylococcus aureus. Cultures for anaerobic bacteria are restricted to endocervical or endometrial aspirates which are submitted to the laboratory in anaerobic transport vials. Cultures for fungi, Chlamydia trachomatis, and Ureaplasma urealyticum are performed by specific request, as is miscroscopic examination for Trichomonas vaginalis. Haemophilus influenzae was identified with the porphyrin test according to the Kilian's taxonomic system. Genital tract specimens from 11 patients yielded H. influenzae in pure or predominant culture. 9 patients were females, of whom 4 had vaginitis, usually with a yellowish, foul smelling discharge. 2 had IUD-related endometritis and parametritis, 1 had an incomplete septic abortion, and 1 had probable urethral syndrome. 2 males had urethritis. Cultures were negative for N. gonorrhoeae in every case and for C. trachomatis in the 6 patients whose specimens were cultured for this agent. Only 2 women -- 1 with vaginitis and 1 with probable urethral syndrome -- had G. vaginalis in cultures of vaginal secretions, while U. urealyticum was isolated from vaginal or cervical secretions of 3 of 4 women cultured for the organism.

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.

Laparoscopic findings in twenty-five failures of artificial insemination.

The laparoscopic findings, treatment, and follow-up of 25 patients who failed artificial insemination donor (AID) were retrospectively evaluated. A high incidence (72%) of abnormal pelvic findings was encountered. Endometriosis was found in 60% and pelvic adhesions in 12% of the patients. The incidence of these two entities was not significantly different from their incidence in patients with unexplained infertility in the same institution (44% for endometriosis and 36% for adhesions). After surgical or medical treatment, a pregnancy rate of 22.2% (16.6% for endometriosis and 66.6% for pelvic adhesions) was achieved in patients with positive pelvic findings; in the group with negative pelvic findings, a pregnancy rate of 20% was achieved. The value of diagnostic laparoscopy in AID failures is discussed in the light of the findings presented and the relatively low rate of post-treatment pregnancy.

Danazol binding to steroid receptors in human uterine endometrium.

To understand the mechanism of action of danazol, the binding of danazol to multiple classes of intracellular steroid binding proteins was studied in the human uterine endometrium. Danazol bound to endometrial receptors for estrogen, progesterone, and androgen and seemed to bind to endometrial intracellular corticosteroid-binding globulin and sex-hormone-binding globulin. Danazol occupies almost all binding sites of steroids in the steroid target cells in spite of the presence of endogenous steroids. It is speculated that the binding behavior of danazol may be related to its therapeutic effect on endometriosis.

PIP: Binding of danazol to multiple classes of intracellular steroid binding proteins was studied in the human uterine endometrium in an effort to understand danazol's mechanism of action. Danazol, which binds to human endometrial cytosol receptors for androgen (AR), progestin (PR), and estrogen (ER), also appears to interact with sex hormone binding globulin and corticosteroid binding globulin present in the cytosol preparations. 17 beta-hydroxy-17 alpha-methyl-estra-4, 9, 11-trine-3-one-[17 alpha-methyl-3h], 87 Ci/mmol (3H-R1881) binds to AR and PR in the human uterine endometirum. Thus, 3H-R1881/PR binding was abolished by the presence of progesterone. Previously reported studies have demonstrated that danazol binds with relatively high affinity to AR. Also, the danazol/AR complex can translocate to the nucleus. These findings are consistent with the observed androgenic effects of danazol in rats and women. Danazol binds with moderate affinity to PR. The danazol/PR complex is poorly translocated to the nucleus, suggesting that danazol is antiprogestational. Yet, a major metabolite of danazol, ethisterone, is progestational. The progestational vs. the antiprogestational effects of danazol remain controversial. Danazol displacement of 6, 7-3H-)stradial-17 beta (3H-E2) from ER is not parallel to E2 displacement of 3H-E2 when compared with that of PR or AR. This discrepancy may derive from an affinity difference. Danazol binds poorly to ER, yet circulating concentrations of danazol in vivo may lead to complete occupancy of the ER by danazol, which may interfere with normal endometrial ER dynamics, resulting in an antiestrogenic effect. Danazol occupies almost all binding sites of steroids in the steroid target cells despite the presence of endogenous steroids. The binding behavior of danazol may be related to its therapeutic effect on endometriosis.

Clinical applications of gonadotropin-releasing hormone and gonadotropin-releasing hormone analogs.

PIP: Investigations have proved the clinical importance of hypothalmic gonadotropin-releasing hormone (GnRH) and its agonistic and antagonistic analogs. A pulsatile pattern of stimulation of specific receptors in the anterior pituitary gonadotrope has been shown to activate pituitary-gonadal function; continuous administration inhibits it. Clinical research has shown promising results in the induction of ovulation using the pulsatile pattern of GnRH administration in patients with hypogonadotropic amenorrhea. Attempts to use GnRH and its agonists to activate the pituitary-gonadal system in patients with idiopathic delayed puberty has proved logistically impractical because of the duration of treatment required to achieve sexual maturation. Treatment of cryptorchidism by intranasal administration 6 times daily for 4 weeks resulted in complete descent in 38% of the 48 boys and partial descent in 28%. For GnRH nonresponders, sequential treatment with human chorionic gonadotropin produced an 86.2% success rate. Because of the ability of GnRH agonists to reversibly suppress the pituitary-gonadal axis without side effects, it can be used in diseases mediated by gonadal steroids. Successful halting of precocious puberty through the administration of GnRH to suppress the nocturnal release of gonadotropin has been demonstrated. Unlike treatment with progestational agents, no side effects are discerned. Continuous administration of GnRH agonist in patients with endometriosis reduces ovarian estrogens and androgens to castration levels, mimicking an ovariectomy. This castration effect highlights the potential use of GnRH agonists in the treatment of metastatic breast cancer. The use of GnRH agonists for the treatment of androgen-dependent prostatic carcinoma has induced clinical improvement with nonmetastatic stage 3 disease and pain relief in metastic stage D disease. In polycystic ovary syndrome, administration of GnRH agonist shows promising results. As a potential contraceptive, GnRH agonists have not yet demonstrated practical advantages. The actions under study include: ovulation inhibition, luteolysis induction, induction of luteal phase defect and reduction of testosterone production. Numerous antagonistic analogs of GnRH have been synthesized and have shown some potential contraceptive effects in animal studies.^ieng

CO2 laser laparoscopy in infertile women with endometriosis and women with adnexal adhesions.

One hundred twenty-four infertile women either with endometriosis (n = 70) or with adnexal adhesions (n = 54) were treated with the carbon dioxide laser used laparoscopically and were followed for 18 months. Removal of endometriotic implants, vaporization of endometrioma capsules, and lysis of adnexal adhesions was accomplished. Postoperative pregnancy rates were as follows: 57% for patients with endometriosis (mild, 62%; moderate, 52%; severe, 42%) and 57% for patients with adnexal adhesions. No serious complications requiring laparotomy were encountered. When performed, second-look laparoscopy confirmed efficient removal of endometriosis.

Ovarian sonographic findings during intermittent intranasal luteinizing hormone-releasing hormone agonist sequentially combined with an oral progestogen as antiovulatory contraceptive approach.

Ovarian ultrasounds were performed in four groups of six or seven women taking intranasal luteinizing hormone-releasing hormone agonist Buserelin (200 micrograms twice daily or 400 micrograms once daily) for periods of 14 or 21 days. Medroxyprogesterone acetate (5 mg by mouth twice daily) was added on days 15 to 21. A pause of 7 days followed each of the four treatment periods. Between days 12 to 15 of the first Buserelin cycle, sonograms showed in 17 cases (68%) various degrees of follicular stimulation ranging from numerous 4- to 10-mm follicles (24%), to 10- to 27-mm developing follicle(s) (24%), to greater than 27-mm ovarian cysts (20%). At the fourth Buserelin cycle, the predominant observation was large follicle(s) in the 14-day schedules, whereas ovarian scans did not reveal follicular stimulation in 66% of the 21-day schedules. The area under estradiol (E2) curves was above control in cycles with induced large follicles mainly in the 14-day schedules at the 200 micrograms/12 hour dose. Occasional brief and low elevation of progesterone was compatible with luteinized follicles. In the 21-day schedules at 400 micrograms/24 hours, absence of follicular development was frequently associated with serum E2 in the early follicular phase range. The most appropriate dosage regimen for potential contraception was 200 micrograms/12 hours for 21 days because it was associated with small follicles and serum E2 was in the range of control cycles.

PIP: This study was aimed at evaluating the ovarian changes during intermittent luteinizing hormone-releasing hormone agonist (LH-RH-A) administration. Ovarian ultrasonic findings were analyzed during 4 successive cycles of LH-RH-A administration in 4 groups of subjects treated with 400 mcg once daily or 200 mcg twice daily of Buserelin and for periods of 14 or 21 days. Intermittent LH-RH-A administration was associated with stimulation of ovarian follicles to various stages of development. After 2 weeks of Buserelin in a 1st treatment cycle, ovarian scans revealed follicular development in 68% of cases--4-10 mm follicles in 24%, 10-27 mm developing follicles in another 24%, and ovarian cysts greater than 27 mm in 20%. At the 4th Buserelin cycle, the predominant finding was large follicles in the 14-day schedules, whereas ovarian scans failed to reveal follicular stimulation in 66% of the 21-day schedules. The most appropriate dosage regimen for potential contraception is 200 mcg/12 hours for 21 days. This regimen was associated with small follicles and serum estradiol was in the range of control cycles.

Hysterectomy performed within 1 year after tubal sterilization.

In the United States, approximately 650,000 women of reproductive age undergo tubal sterilization each year and some of these women later have hysterectomies. Little is known about risk factors for having hysterectomy after tubal sterilization. For examination of this issue, we analyzed data from the Collaborative Review of Sterilization, an ongoing multicenter prospective study designed to assess the safety and efficacy of female sterilization operations. In 1979 and 1980, 4002 women 15 to 44 years of age had interval tubal sterilization; of these women, 64 had hysterectomies within 15 months, which yielded a cumulative incidence of 1.6%. Women with a history of menstrual complaints, leiomyomata, ovarian cysts, or endometriosis before their tubal sterilization had an increased risk of hysterectomy, compared with women without such a history. However, 98% of women with a history of these conditions did not have a hysterectomy within 15 months after tubal sterilization. Further follow-up of these women should help to better delineate their long-term risks.

Second-look laparoscopy in infertility surgery: therapeutic and prognostic value.

Sixty infertile women underwent infertility surgery followed by "second-look laparoscopy" (SLL). All these women had undergone detailed fertility workups, including a diagnostic laparoscopy prior to surgery. The tuboovarian adhesive disease was staged according to the severity of the disease and compared with findings at SLL. Sixty percent of adnexa showed improvement at SLL. During SLL, newly formed adhesions were lysed and stenotic fimbrial ostia dilated. Optimal time for SLL was 4 to 8 weeks after surgery. From these observations, we suggest that SLL provides further opportunity to lyse re-formed adhesions and may have prognostic and therapeutic benefits after laparotomy for lysis of adhesions.

Unsuspected chronic pelvic inflammatory disease in the infertile female.

Diagnostic laparoscopy performed during an infertility evaluation identified 80 patients with hydrosalpinges (12% of all laparoscopic examinations performed for infertility). Despite these findings, only 20 (25%) of these patients reported a prior episode of acute pelvic inflammatory disease (PID), and only 18 (22.5%) had complaints of pelvic pain. Compared with a matched group of infertility patients with no endoscopic evidence of prior pelvic infection, those patients with hydrosalpinges were more likely to have used an intrauterine device and were less likely to have used an oral contraceptive. Since "silent" PID is a potential cause of infertility, endoscopic visualization of the female reproductive organs should be considered during the infertility evaluation. Moreover, in view of its insidious nature, the diagnosis of PID should be considered in a young sexually active patient with gynecologic complaints.

Peritoneal endometriosis in women requesting reversal of sterilization.

Seventy-six women requesting reversal of sterilization underwent at least 1 operative procedure during a 27-month period, and 14 (18.4%) were found to have pelvic endometriosis. The endometriosis patients were noted to have had significantly fewer pregnancies (1.8 versus 2.9, P less than 0.01) before sterilization than those without endometriosis, but the two groups did not differ significantly in mean age (30.8 versus 30.3 years), type of sterilization or in mean number of years since sterilization (5.0 versus 5.5 years). In only two individuals were proximal tubal segment fistulas found at the time of reversal, and neither had endometriosis. We conclude that pelvic endometriosis is more common in patients with bilateral tubal occlusion than previously suspected and that its presence indicates that endometriosis implants can persist for prolonged periods of time, can give rise to new implants, or do not require the tubal reflux of menstrual debris to form.

Diethylstilbestrol exposure in utero and endometriosis in infertile females.

Endometriosis was found in 39% and in utero diethylstilbestrol (DES) exposure in 5% of 397 infertile women who had undergone laparoscopy and/or laparotomy among 750 consecutively evaluated infertile couples. Fifty percent of the DES-exposed infertile women also had endometriosis, similar to the 39% with endometriosis among non-DES-exposed women. Cervical stenosis was found in 25% of all DES-exposed patients and in 83% of those who had undergone cryocautery or conization. However, 40% did not have endometriosis. Thus, while the frequency of endometriosis and cervical stenosis is extremely high in infertile women exposed in utero to DES, a significant association beyond that found in non-DES-exposed patients could not be established. Some of the infertility may be associated with cervical stenosis alone.

PIP: Endometriosis was found in 39% and in utero diethylstilbestrol (DES) exposure in 5% of 397 infertile women who had undergone laparoscopy and/or laparotomy among 750 consecutively evaluated infertile couples. 50% of the DES exposed infertile women also had endometriosis, similar to the 39% with endometriosis among non-DES exposed women. Cervical stenosis was found in 25% of all DES-exposed patients and in 83% of those who had undergone cryocautery or conization. However, 40% did not have endometriosis. Thus, while the frequency of endometriosis and cervical stenosis is extremely high in infertile women exposed to DES in utero, a significant association beyond that found in non-DES exposed women could not be established. Some infertility may be associated with cervical stenosis alone.

Intranasal peptide contraception by inhibition of ovulation with the gonadotropin-releasing hormone superagonist nafarelin: six months' clinical results.

Forty-seven woman volunteers used a new highly potent stimulatory analog of the hypothalamic gonadotropin-releasing hormone (GnRH) for contraception. The superagonist nafarelin acetate, D-Nal(2)6-GnRH, was administered intranasally in one daily dose of 125 micrograms to 25 women and 250 micrograms to 22 women. Ovulation was consistently inhibited during 261 of 262 treatment months. No pregnancy occurred during 222 months in which no additional contraceptives were used. The mean plasma estradiol level after 6 months of treatment was 162 pmol/l. The predominant bleeding pattern was oligomenorrhea. Three women on the lower dose and six women on the higher dose discontinued the trial prematurely, mainly because of hot flushes. No serious side effects were reported. Ovulatory menstruations returned after a median time of 43 days after discontinuation of therapy. Daily intranasal nafarelin treatment for inhibition of ovulation proved to be an effective and rapidly reversible method of contraception.