How do elevated levels of testosterone affect the function of the human fallopian tube and fertility?-New insights.

Excess testosterone levels affect up to 20% of the female population worldwide and are a key component in the pathogenesis of polycystic ovary syndrome. However, little is known about how excess testosterone affects the function of the human fallopian tube-the site of gamete transport, fertilization, and early embryogenesis. Therefore, this study aimed to characterize alterations caused by long-term exposure to male testosterone levels. For this purpose, the Fallopian tubes of nine female-to-male transsexuals, who had been undergoing testosterone treatment for 1-3 years, were compared with the tubes of 19 cycling patients. In the ampulla, testosterone treatment resulted in extensive luminal accumulations of secretions and cell debris which caused ciliary clumping and luminal blockage. Additionally, the percentage of ciliated cells in the ampulla was significantly increased. Transsexual patients, who had had sexual intercourse before surgery, showed spermatozoa trapped in mucus. Finally, in the isthmus complete luminal collapse occurred. Our results imply that fertility in women with elevated levels of testosterone is altered by tubal luminal obstruction resulting in impaired gamete transport and survival.

Endometrial tubal metaplasia in a young puerperal woman after breast cancer.

INTRODUCTION: Tamoxifen is the usual endocrine (anti-estrogen) therapy for hormone receptor-positive breast cancer in pre and post-menopausal women. Previous studies have suggested an increased prevalence of endometrial diseases after treatment with tamoxifen. CASE PRESENTATION: The authors report a case of 38-year-old woman with diagnosis of endometrial polyp and tubal metaplasia, during puerperium and after micropapillary ductal breast cancer surgery, 5 years of tamoxifen treatment, spontaneous pregnancy without complications and full-term vaginal delivery. CONCLUSION: Tamoxifen is a safe and reliable treatment of breast cancer, but data suggest an association with endometrial polyps, hyperplasia, metaplasia and carcinoma. One of the most common types of endometrial metaplasia is ciliated tubal metaplasia. It is generally known that endometrial tubal metaplasia is a benign disease. However studies propose endometrial tubal metaplasia to be a potential premalignant endometrial lesion and its association with endometrial hyperplasia and well-differentiated endometrioid carcinoma. We propose close monitoring of patients taking tamoxifen and prompt evaluation of any uterine bleeding or pelvic complaint or abnormal TVUS images.

Co-occurrence of atypical endometriosis, subserous uterine leiomyomata, sactosalpinx, serous cystadenoma and bilateral hemorrhagic corpora lutea in a perimenopausal adipose patient taking tamoxifen (20 mg/day) for invasive lobular breast cancer.

BACKGROUND: For women taking tamoxifen, recent data strongly support the estrogen agonist role of tamoxifen as a causal factor for the increased risk of endometriosis, but also of leiomyomata, endometrial polyps, and endometrial hyperplasia. CASE REPORT: A 54-year-old perimenopausal woman on tamoxifen (20 mg/day), gravida 0, with surgically treated invasive lobular breast cancer and extensive lobular carcinoma in situ (pT2 (m) pN0 (snl) pL0 G2 pTis (LCLIS) R0 M0 Ki-67 1%, ER+, PR+, Her-2-neu-negative) was referred for evaluation of a pelvic mass. The ultrasonographic examination showed a regular endometrium of less than 6 mm thickness, a uterine myoma (approximately 3 cm in diameter), a right-sided sactosalpinx (7.7 x 3.6 x 5.7 cm), an ovarian cyst on the right side (approximately 4 cm), and a left-sided ovarian cyst (approximately 3 cm in diameter) without any malignancy criteria. The CA-125 level was normal (9.4 U/ml). With the exception of a decreased serum progesterone level; the endocrine status showed no sign of ovarian insufficiency (LH 5.6 mIU/ml, FSH 9.0 mIU/ml, estradiol 103.7 pg/ml, progesterone 1.51 ng/ml, testosterone 0.11 ng/ml, DHEA-S 62.3 microg/dl, SHBG 64.39 nmol/l, free androgen index 0.6). During laparoscopy 2 uterine subserous leiomyomata, a right-sighted sactosalpinx, bilateral ovarian cysts, and an extended polypoid, vascularized endometriosis of the bladder peritoneum, the pelvic wall and Douglas pouch were found. Complete pelvic deperitonealization, bilateral adnexectomy, and also enucleation of the 2 leiomyomata were performed. RESULTS: Pathological examination confirmed the sactosalpinx. In the cystic ovary (right side), a serous cystadenoma close to a hemorrhagic corpus luteum (HCL) was diagnosed. The left ovary showed another HCL. The removed leiomyomata did not show atypia or significant mitotic activity. The endometriotic lesions presented strong expression of the estrogen receptor, the progesterone receptor, and the proliferation marker MIB-1. In addition, there was no HER-2-neu expression. A switch to the aromatase inhibitor letrozol was recommended. CONCLUSION: The possibility of tamoxifen-induced or tamoxifen-driven endometriosis in peri- or postmenopausal patients with breast cancer should be considered.

Fallopian damage induced by organophosphate insecticide methyl parathion, and protective effect of vitamins E and C on ultrastructural changes in rats.

The aim of the present study was to examine the effects of subchronic methyl parathion (MP) administration on lipid peroxidation and fallopian tube damage, and to evaluate the preventive effects of the use of vitamins E and C against toxicity. The experimental groups were: rats treated with corn oil (control group), with 5 mg/kg MP and with 5 mg/kg body weight MP plus vitamins E and C (MP + Vit). The groups were given MP by oral gavage for five days a week for four weeks at a daily dose of 5 mg/kg (MP and MP + Vit) using corn oil as a vehicle. Vitamins E and C were injected at doses of 50 mg/kg intramuscularly and 20 mg/kg intraperitoneally, respectively, just after the treatment with MP in the MP + Vit group. The levels of malondialdehyde (MDA) were determined in rat plasma. Electron microscopic ultrastuructural and histopathological changes in the fallopian tissue were examined. MDA levels were higher in the MP group than in the control group, and lower in the MP + Vit group than in the MP group. MP led to deletions in microvilli and marked loss in kinocillia of surface epithelium. But these marked histopathological findings decreased in the MP + Vit group. Multiple doses of MP administration caused some damage in the fallopian tube, and treatment with vitamins E and C after MP could reduce this effect.

Endometriosis arising during estrogen and testosterone treatment 17 years after abdominal hysterectomy: a case report.

OBJECTIVE: To report the possible association between the use of oestrogen replacement therapy and endometriosis in a postmenopausal woman. METHODS: We present a case of a postmenopausal, previously hysterectomised, woman who received hormonal replacement therapy and developed a large broad ligament cyst. Two years prior to her presentation she had been complaining of pelvic pain and deep dyspareunia. RESULTS: Pelvic ultrasound showed an adnexal cyst that was increasing in size. CA-125 was normal. Laparoscopy revealed multiple endometriotic deposits and a broad ligament cyst. Cystectomy and oophorectomy were done. Histology confirmed a diagnosis of endometriosis including the broad ligament cyst. CONCLUSIONS: Hormonal replacement therapy can be associated with de novo endometriosis including at sites, which are unusual.

Paraovarian cystic endosalpingiosis in association with tamoxifen therapy.

This report describes a case of macroscopically visible cystic endosalpingiosis involving the paraovarian region in a woman who had been taking tamoxifen for breast cancer. A 2.5 cm multicystic lesion was seen on the external surface of the right ovary and histological examination showed a mass of dilated glands lined by ciliated tubal-type epithelium and set in a fibrovascular stroma. Cystic endosalpingiosis resulting in a tumour-like mass is a rarely described entity which is probably not well recognised by histopathologists. Although unlikely to be mistaken for malignancy, the lesion may result in diagnostic confusion. The role of tamoxifen in the development of the lesion in the present case is not clear but the oestrogenic effects of this drug may have contributed to its formation.

[Tubo-ovarian actinomycosis, intrauterine device and chemotherapy for breast cancer]. / Actinomycose tubo-ovarienne, stérilet et chimothérapie pour cancer du sein.

Tubo-ovarian actinomycosis was observed after chemotherapy for breast cancer in a patient with an intrauterine device. Does chemotherapy increase the risk? How can it be prevented?

Selective embryo reduction in a heterotopic pregnancy using potassium chloride injection resulting in a hematosalpinx.

OBJECTIVE: To incorporate conservative management of a heterotopic pregnancy using injection of KCl into the ectopic pregnancy (EP). DESIGN: A retrospective case report. SETTING: A patient referred to an academic institution in the division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, incorporating the ultrasound (US) and operating room facilities. INTERVENTION(S): Using US as a guide, KCl was injected into the chorionic cavity of an EP. MAIN OUTCOME MEASURE(S): Resolution of ectopic gestational tissue with resultant hematosalpinx requiring exploratory laparotomy. Uncomplicated prenatal course of intrauterine pregnancy. RESULT(S): Injection of KCl into the chorionic cavity of EP resulting in resolution of gestational tissue but complicated by hematosalpinx in the fallopian tube. CONCLUSION(S): Selective embryo reduction of a tubal heterotopic pregnancy remains a viable therapeutic option.

Late complications after systemic methotrexate treatment of unruptured ectopic pregnancies: a report of three cases.

BACKGROUND: The use of methotrexate (MTX) by systemic administration in the treatment of unruptured ectopic pregnancy has been reported as a safe and effective method. CASES: We report three cases (one hematosalpinx and two pelvic hematocoeles) of complications after the use of MTX in the treatment of unruptured ectopic pregnancies. All three cases came to our observation for pelvic pain, abnormal bleeding and a pelvic mass after an interval of 3-5 months, subsequent to the disappearance of symptoms and normalization of serum human chorionic gonadotropin beta-subunit (beta-hCG) levels. CONCLUSIONS: These findings suggest that: (a) such complications should be considered before selecting the mode of treatment for ectopic pregnancy; and (b) that an early ultrasonographic control should be performed after MTX treatment even when the decline in beta-hCG levels suggests a successful resolution. This would permit an early diagnosis of these late complications.

Relation of female infertility to consumption of caffeinated beverages.

Several studies have reported an association between caffeine intake and delay to conception. To study this relation further, the authors examined caffeine use in 1,050 women with primary infertility and 3,833 women who had recently given birth during the period 1981-1983 in the United States and Canada. The cases were separated by the cause of their infertility: ovulatory factor, tubal disease, cervical factor, endometriosis, or idiopathic infertility. The relative risks of each type of infertility associated with caffeine were calculated using separate logistic regression models and controlling for relevant confounding factors, such as age, center, cigarette smoking, lifetime number of sexual partners, alcohol consumption, contraception, body mass index, and exercise. A significant increase in the risk of infertility due to tubal disease or endometriosis was observed for the upper levels of caffeine intake, indicating a threshold effect. For tubal infertility, a relative risk of 1.5 (95% confidence interval (CI) 1.1-2.0) was found in women who consumed more than 7 g of caffeine per month as compared with those who consumed 3 g or less per month. For endometriosis, the relative risk was 1.9 (95% CI 1.2-2.9) in women who consumed 5.1-7 g/month and 1.6 (95% CI 1.1-2.4) in those with an intake of more than 7 g/month. These data suggest that caffeine deserves further study with regard to its effects on the female reproductive system.

Effects of contrast agents on the fallopian tube in a rabbit model.

The authors evaluated the effect of different iodinated contrast agents on the fallopian tube and adnexal tissue in 15 rabbits. Ethiodized oil, an oil-soluble agent, was used in five rabbits. The following water-soluble agents were used: iothalamate meglumine 30% (n = 3), iothalamate meglumine 60% (n = 3), and ioxilan (n = 4). The agents were injected through catheters placed in the fallopian tubes. Fallopian tubes and peritoneal cavities were histologically evaluated. The contralateral tube served as a control. Ioxilan and iothalamate meglumine 30% produced no pathologic response in the tube or peritoneal cavity. Iothalamate meglumine 60% was associated with mild inflammatory infiltrate, mucosal edema, giant cell reaction, and periovarian adhesions that were bilateral but more pronounced on the injected side. Use of ethiodized oil resulted in papillary fibrous adhesions on the ovarian surface, and fat granulomas were seen in the periovarian tissues. The safety of oil-based contrast agents for use in hysterosalpingography is therefore questioned. No significant differences were found among the water-soluble contrast agents.

Recreational drug use and the risk of primary infertility.

Recreational drug (marijuana, lysergic acid diethylamide or LSD, speed, cocaine, and "other") exposures of women with primary infertility were compared with those of a matched control group of women with proven fertility. Women who reported smoking marijuana had a slightly elevated risk for infertility due to an ovulatory abnormality (RR = 1.7, 95% CI = 1.0 to 3.0). The risk was greatest among women who had used marijuana within one year of trying to become pregnant (RR = 2.1, 95% CI = 1.1 to 4.0). No consistent frequency or duration of use effects could be demonstrated, and the risk was confined to low-frequency users. Risks associated with the use of other drugs were not elevated. The risk of infertility from a tubal abnormality associated with cocaine use was greatly increased (RR = 11.1, 95% CI = 1.7 to 70.8). Our results are consistent with animal studies suggesting that smoking marijuana may cause a transient disruption of ovulatory function. The possibility that cocaine exposure influences the development of tubal infertility needs further investigation.

Genital tract abnormalities in female rats exposed to diethylstilbestrol in utero.

Genital tract morphology in 14-month old female rats exposed prenatally to diethylstilbestrol (DES) was analyzed as part of an examination of the effects of transplacental exposure to DES on estrogen sensitive tissues. Pregnant Sprague-Dawley rats were injected with sesame oil alone or with DES in sesame oil on days 10 and 13 of gestation (total dose 1.2 micrograms DES) or on days 15 and 18 (total dose 1.2 micrograms or 120 micrograms DES). Female offspring (9-15 per group) were sacrificed at 14 months of age. Effects of DES exposure varied with the dose given and with the stage of differentiation of the fetal tissues. In the ovaries of rats exposed to 120 micrograms of DES on days 15 and 18 of gestation, follicular elements were reduced and replaced by dense sheets of stromal cells; oophoritis was noted in five of nine rats. Hypercellularity of oviductal stroma was another common feature, as was suppurative salpingitis. Ovaries of rats exposed to 1.2 micrograms DES on days 10 and 13 of gestation were more likely to contain numerous corpora lutea than the other DES-exposed groups of controls. An increased incidence of benign uterine abnormalities was observed in DES-exposed offspring, including squamous metaplasia and suppurative endometritis. In the cervices of all nine rats exposed to 120 micrograms DES on days 15 and 18 of gestation, the epithelial surface showed a convoluted pattern, lined by stratified squamous and stratified cuboidal cells. Thus, prenatal exposure to DES, especially at the higher dose used, has long-term consequences on reproductive tract morphology in Sprague-Dawley rats.

Abnormalities in the reproductive system of aged mice after neonatal estradiol exposure.

Female mice of the BALB/c strain were treated neonatally with 17 beta-estradiol (E2) or sesame oil and sacrificed at 20 months of age. Neonatal treatment of mice with E2 resulted in the development of vaginal lesions, including adenosis, adenocarcinoma and squamous-cell carcinoma. While the neonatal treatment also induced squamous metaplasia in the uterine epithelium, development of uterine adenomatous hyperplasia was markedly inhibited in the estrogen-treated mice when compared to the oil-treated controls. However, neonatal exposure to E2 resulted in a high incidence of ovarian tumors and epithelial hyperplasia of the oviduct. Thus, the effects of neonatal treatment with estrogen appeared to interact with the usual effects of aging, modifying the development of pathological abnormalities in the various reproductive organs of mice.

The effects of E. coli endotoxin on the tubal mucosa of the rabbit. A scanning electron microscopic study.

E. Coli endotoxin (5 mg/ml) was injected into the lumen of the right fallopian tube of 25 rabbits. The left tubes, injected with saline, served as controls. The luminal surface of the epithelium of the oviducts was examined by a scanning electron microscope at various intervals after the injection. The damage that was caused by the endotoxin, was found to be maximal by 24 hours after injection. The damage was comprised of adhesions of shortened and swollen cilia and smoothened appearance of the secretory cells due to shortening and swelling of the microvilli. In some areas the epithelium was denuded of cilia. A relative rapid process of repair of the epithelium begins thereafter and by 72 hours, restoration of normal architecture of the mucosa was almost completed. The contralateral control tubes were not affected by the endotoxin. The possible influence of local gram negative bacterial infections, liberating large amounts of endotoxin,on the reproductive capacity is discussed.