The obesogen tributyltin induces abnormal ovarian adipogenesis in adult female rats.

Tributyltin chloride (TBT) is an obesogen associated with various metabolic and reproductive dysfunctions after in utero exposure. However, few studies have evaluated TBT's obesogenic effect on adult ovaries. In this study, we assessed whether TBT's obesogenic effects resulted in adult ovarian adipogenesis and other reproductive abnormalities. TBT was administered to adult female Wistar rats, and their reproductive tract morphophysiology was assessed. We further assessed the ovarian mRNA/protein expression of genes that regulate adipogenesis. Rats exposed to TBT displayed abnormal estrous cyclicity, ovarian sex hormone levels, ovarian follicular development and ovarian steroidogenic enzyme regulation. Rats exposed to TBT also demonstrated abnormal ovarian adipogenesis with increased cholesterol levels, lipid accumulation, and PPARγ, C/EBP-ß and Lipin-1 expression. A negative correlation between the ovarian PPARγ expression and aromatase expression was observed in the TBT rats. Furthermore, TBT exposure resulted in reproductive tract atrophy, inflammation, oxidative stress and fibrosis. Ovarian dysfunctions also co-occurred with the uterine irregularities. Abnormal ovarian adipogenic markers occurring after TBT exposure may be associated with uterine irregularities. A positive correlation between the ovarian cholesterol levels and uterine inflammation was observed in the TBT rats. These findings suggest that TBT leads to ovarian obesogenic effects directly by abnormal adipogenesis and/or indirectly through adult reproductive tract irregularities.

Evaluation of pelvic inflammatory disease potential in cholinesterase inhibitor pesticide-exposed females.

Cholinesterase inhibitor pesticides, mainly organophosphates and carbamates, are commonly used in Egypt. Chronic exposure of males and females working in agriculture is expected. The study aimed to relate exposure to cholinesterase inhibitor pesticides to the development of pelvic inflammatory disease (PID). This is a case-control study that was conducted among 84 females. Seventy patients complained of pelvic inflammatory disease visited the outpatient Gynecology and Obstetrics Clinic. Fourteen females were not suffering from PID and were chosen as a control group. Red blood cells' cholinesterase activity was measured in blood. Cervical swaps were collected, and cultures were submitted for microbiological examination. The results showed that cholinesterase activities were significantly depressed in exposed females (6.36 ± 0.8 µmoles/min/ml red cells) when compared to non-exposed (7.5 ± 1.2 µmoles/min/ml red cells), and both were significantly depressed when compared with healthy females (9.17 ± 0.7 µmoles/min/ml red cells). The correlation coefficient (r) between previous exposure and the laboratory confirmed cervical infection was 0.31, with a P value of 0.009. The study concluded that exposure to cholinesterase inhibitor pesticides could increase the occurrence of pelvic inflammatory disease.

Assessment of urinary cotinine levels in women with gynecological complaints at a tertiary care hospital: A pilot study.

Gynecological effects due to smokeless tobacco exposure are not well studied. This cross-sectional study was undertaken with the objective to evaluate the urinary cotinine levels in women of reproductive age with gynecological complaints. The study was conducted in 2015 at the outpatient clinic of the Department of Obstetrics and Gynecology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi. A total of 192 consecutive women presenting with gynecological complaints (pelvic inflammatory disease (PID), infertility, and menstrual abnormality) were recruited. Their demographic details and tobacco exposure were recorded. All of them denied exposure to any form of tobacco. Urinary cotinine level of each participant was measured. The mean urinary cotinine level was 23.60 ± 12.00 ng/ml. PID was the most common gynecological complaint. Women with PID had significantly higher urinary cotinine levels compared to those with menstrual complaints and infertility: 24.9548 (±12.259) ng/ml versus 20.2042 (±10.9248) ng/ml. This study highlights the importance of addressing the issue of secondhand smoke exposure and reproductive morbidities in women.

Establishment of hydrochloric acid/lipopolysaccharide-induced pelvic inflammatory disease model.

Pelvic inflammatory disease (PID), which is one of the most problematic complications experienced by women with sexually transmitted diseases, frequently causes secondary infections after reproductive abnormalities in veterinary animals. Although the uterus is self-protective, it becomes fragile during periods or pregnancy. To investigate PID, bacteria or lipopolysaccharide (LPS) extracted from gram negative bacteria has been used to induce the disease in several animal models. However, when LPS is applied to the peritoneum, it often causes systemic sepsis leading to death and the PID was not consistently demonstrated. Hydrochloric acid (HCl) has been used to induce inflammation in the lungs and stomach but not tested for reproductive organs. In this study, we developed a PID model in mice by HCl and LPS sequential intracervical (i.c.) administration. The proinflammatory cytokines, interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α, were detected in the mouse uterus by western blot analysis and cytokine enzyme-linked immunosorbent assay after HCl (25 mg/kg) administration i.c. followed by four LPS (50 mg/kg) treatments. Moreover, mice exhibited increased infiltration of neutrophils in the endometrium and epithelial layer. These results suggest that ic co-administration of HCl and LPS induces PID in mice. This new model may provide a consistent and reproducible PID model for future research.

The anti-inflammatory and anti-nociceptive activities of Patrinia villosa and its mechanism on the proinflammatory cytokines of rats with pelvic inflammation.

This study explores the anti-inflammatory and anti-nociceptive activities of Patrinia villosa, a Chinese medicinal plant, and to explore its effects on the proinflammatory cytokines of the rats with pelvic inflammation model. The animals were randomly divided into Patrinia villosa group (PV group), dexamethasone group (DEX group), and model-control group (CON group) to perform an ear edema test, a carrageenin-induced paw edema test, a cotton pellet-induced granuloma formation test, and an acetic acid-induced writhing test. The model rats with pelvic inflammation were established, and the serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) in each group was detected with the Enzyme-Linked ImmunoSorbent Assay (ELISA). The results of the ear edema test, carrageenin-induced paw edema test, cotton pellet-induced granuloma formation test, and acetic acid-induced writhing test all showed that Patrinia villosa had strong anti-inflammatory and anti-nociceptive effects. In the experiment using model rats with pelvic inflammation, we found that the serum levels of IL-6, IL-8 and TNF-α in PV and DEX group were all significantly lower than those of the CON group, and the serum levels of IL-6 and IL-8 in PV group were significantly lower than those of the DEX group. Patrinia villosa, with its strong anti-inflammatory and anti-nociceptive activities, can be used to treat pelvic inflammation and to relieve the associated pain.

Safety of quinacrine contraceptive pellets: results from 10-year follow-up in Vietnam.

BACKGROUND: This study was conducted to evaluate long-term safety of quinacrine pellets for nonsurgical sterilization among women in Vietnam. STUDY DESIGN: Observational cohort study of 2735 women who had quinacrine insertions between 1989 and 1993 compared to 1623 women who received an intrauterine device (IUD). RESULTS: Cumulative follow-up times for the quinacrine and IUD cohorts were 28,697 and 17,382 person-years, respectively, and losses to follow-up were 6% and 7%, respectively. Quinacrine users had a higher incidence of ectopic pregnancy compared to IUD users (risk ratio, 2.2; 95% confidence interval, 1.06-4.54); the risks of cancer, hysterectomy, pelvic/gynecologic surgery and death were similar in the two groups. Two quinacrine insertions appeared to lower the risk of ectopic pregnancy to that of surgical tubal occlusion. CONCLUSIONS: Use of quinacrine in this cohort appeared to have minimal health risks. Other research, including preclinical studies, needs to be considered in an overall evaluation of whether the combination of safety and efficacy provide a basis for quinacrine's approval by appropriate regulatory agencies.

Spontaneous inflammatory pelvic disease in adult non-castrated female rats treated with estrogen.

The adaptive immune response of the genital tract is under the control of sexual steroids; however, the influence of sex hormones on innate immune mechanisms of the genital mucosa are only beginning to be understood. We found that long-term estrogen treatment increases the risk for inflammatory pelvic diseases in adult non-castrated female rats. Female rats (110 g to 130 g) received estrogen (10 rats; 17-beta estradiol, 50 mg pellet; 10 rats: subcutaneous weekly injection of estradiol valerate 0.166 mg/kg). Ten rats received a pellet of 17-beta estradiol and were treated with amoxicillin, 50 mg/kg after the 90th day of exposure to estrogen. Three control groups of ten rats were also used. The estrogen-treated rats developed an inflammatory pelvic disease, with abscess formation after the third month of hormonal treatment. All the surviving animals were killed after six months of hormonal exposure. Among 15 survivors of the two groups that received estrogen 13 animals presented tuboovarian abscesses. Among eight survivors of the group treated with amoxicillin, six had tuboovarian abscesses. None of the 30 control rats presented macro or microscopic signs of inflammatory disease in the uterus, tubes or ovaries. We conclude that estrogen impairs the defense mechanisms of the genital tract of non-castrated female rats, enhancing bacterial growth in the vagina and ascending infection to the uterus, tubes and ovaries.

Spontaneous inflammatory pelvic disease in adult non-castrated female rats treated with estrogen

The adaptive immune response of the genital tract is under the control of sexual steroids; however, the influence of sex hormones on innate immune mechanisms of the genital mucosa are only beginning to be understood. We found that long-term estrogen treatment increases the risk for inflammatory pelvic diseases in adult non-castrated female rats. Female rats (110 g to 130 g) received estrogen (10 rats; 17-beta estradiol, 50 mg pellet; 10 rats: subcutaneous weekly injection of estradiol valerate 0.166 mg/kg). Ten rats received a pellet of 17-beta estradiol and were treated with amoxicillin, 50 mg/kg after the 90th day of exposure to estrogen. Three control groups of ten rats were also used. The estrogen-treated rats developed an inflammatory pelvic disease, with abscess formation after the third month of hormonal treatment. All the surviving animals were killed after six months of hormonal exposure. Among 15 survivors of the two groups that received estrogen 13 animals presented tuboovarian abscesses. Among eight survivors of the group treated with amoxicillin, six had tuboovarian abscesses. None of the 30 control rats presented macro or microscopic signs of inflammatory disease in the uterus, tubes or ovaries. We conclude that estrogen impairs the defense mechanisms of the genital tract of non-castrated female rats, enhancing bacterial growth in the vagina and ascending infection to the uterus, tubes and ovaries.

Compelling reasons for recommending IUDs to any woman of reproductive age.

The intrauterine device (IUD) is a highly effective method of contraception that, as opposed to other countries around the world, is underutilized in the United States by women of all ages. Lingering concerns about the safety of IUDs are in large part responsible for their lack of adoption, but a systematic review published recently nullified some of the major safety concerns about IUD use. The author summarized the methodologically sound evidence regarding the risk of upper-genital-tract infection and infertility associated with IUD use and reported that a slightly increased risk of pelvic inflammatory disease (PID) exists only in the first month following IUD insertion; that the risk of PID in women with symptomless sexually transmitted diseases (STDs) having an IUD inserted is similar to the risk in women not having an IUD inserted; and that there appears to be no negative effect on fertility following IUD removal. In addition, Mirena provides noncontraceptive benefits, such as treatment for menorrhagia, dysmenorrhea, and anemia, and ParaGard may help protect against endometrial cancer. An IUD is also a safer alternative to sterilization for perimenopausal women seeking a long-term and also reversible method of contraception. While both IUDs are suitable for many women of all ages, there are differences in their mechanisms of action, physical characteristics, and clinical effects that make each more or less appropriate for certain women.

Safety of implantable contraceptives for women: data from observational studies.

Contraceptive implants are registered in over 60 countries and have been used by millions of women for three decades. This article reviews findings from observational studies on the safety of contraceptive implants and examines the risk of specific health outcomes. Fifty-five articles were reviewed, and the body of evidence for each health outcome was summarized. Available evidence suggests that contraceptive implants are safe and, overall, implant users do not experience adverse events at rates higher than women not using implants. With respect to specific outcomes, the evidence suggests no increased risks of pelvic inflammatory disease, decreased bone mineral density, anemia, thrombocytopenia, or death with implant use. The evidence was too limited to draw meaningful conclusions for neoplastic disease, cardiovascular events, and HIV/AIDS. Nonsignificantly elevated associations were reported for diabetes, serious mental disorders, and rheumatoid arthritis. Conditions for which risks were marginally, yet significantly, elevated were hypertension and gall bladder disease.

Long-term follow-up after quinacrine sterilization in Vietnam. Part II: interim safety analysis.

OBJECTIVE: To determine the long-term safety of nonsurgical sterilization with quinacrine. DESIGN: Observational cohort study. SETTING: Rural provinces in northern Vietnam. PATIENT(S): Two thousand eight hundred forty women who had had quinacrine insertions and an age-matched comparison group of 1,658 women who had an intrauterine device (IUD) insertion between 1989 and 1993. METHOD(S): Interviews in 1994, 1995, and 1996 and review of available medical records. This is a planned interim analysis. MAIN OUTCOME MEASURE(S): Ectopic pregnancies and the occurrence of other adverse health events. RESULT(S): Over 90% of women were interviewed at least once. Despite matching on age, the groups differed on baseline parity. The ectopic pregnancy rates were similar after either one or two insertions and were similar to the rate of ectopic pregnancies after surgical sterilization in the United States. The quinacrine group reported more gynecologic health problems than the IUD group. However, after correcting for information bias, there was no dose-response effect between the one- and two-insertion quinacrine groups, suggesting the possibility of recall bias or differing baseline health status. CONCLUSION(S): Ectopic pregnancies do not appear to be increased compared with U.S. surgical sterilization rates. The data on other adverse events are more difficult to interpret.

[A guide for women with HIV/AIDS]. / Guia para mujeres con VIH/SIDA.

AIDS: Women make up twelve percent of the AIDS cases in the United States. AIDS research has not been as aggressive for women as it has been for men. Women have different social, psychological, and physiological aspects. An HIV-positive woman must inform her lover of her status for their protection and safer sex methods need to be used. An HIV-positive woman should seek out support groups to find others in similar situations. Stress management is essential. Physically, little is known about the correlation between HIV, menstruation and hormone production. HIV-positive women report increased menstrual irregularities. Researchers are unsure if these irregularities are due to HIV-related hormone changes or drug side effects. Non-prescription medications are available to relieve some discomforts. Regular routine gynecological exams, including Pap smears, are extremely important in detecting early signs of cervical cancer. Pelvic inflammatory disease and its treatment are discussed. During pregnancy, the fetus can contract HIV, as can a nursing baby. Prenatal care is vital. AZT and other studies are discussed. References and a hotline number are provided.^ieng

Reduced risk of pelvic inflammatory disease with injectable contraceptives.

PIP: As part of a study on acute febrile pelvic inflammatory disease and IUDs, reported elsewhere, a significantly lower risk of PID was observed in women using injectable contraceptives. The World Health Organization coordinated the multinational case-control study in 1979-79. Diagnostic criteria were fever, suprapubic tenderness with guarding, cervical or adnexal tenderness or a pelvic mass. 319 cases and 639 matched controls were matched for age, parity, marital status and hospital status. Data were taken from questionnaires. 10 cases (3.1%) currently used injectable contraceptives, mainly Depo-Provera, compared to 38 controls (6.0%). Thus the risk of getting PID was half as great among injectable users, similar in magnitude to risks reported for women using oral contraceptives, barrier methods and sterilization in developing countries.^ieng

[Early inflammatory complications in induction of abortion by means of intrauterine extra-amnial administration of prostaglandin F 2 alpha in primigravidae]. / Entzündliche Frühkomplikationen bei der Abortinduktion durch intrauterine extraamniale Applikation von Prostaglandin F 2 alpha bei Erstgraviden.

PIP: Prostaglandin F2 alpha was used to induce abortion in 287 primigravidae, aged 13-44 (average age 17.5), who were 6-12 weeks pregnant. A solution of 5 mg prostaglandin to 20 ml isotonic salt solution was instilled extraamnially in 3 ml dosages at 1 hour intervals. If more than 8 instillations were required, the dosage was increased to 4-6 ml. In 61.3% of the patients, incomplete abortion was observed. In 30.3%, an additional minor Hegar dilatation was necessary. In 6.3%, complete Hegar dilatation was easily performed. The failure rate was 2.1%. There were 3 cases of endometritis, 9 of salpingitis, and 11 of adnexitis. The average postoperative hospitalization period was 6.7 days.^ieng

[Gonadal function of rats following pre- or postnatal administration of some hormones (author's transl)]. / Die Keimdrüsenfunktion der Ratte nach prae- oder postnataler Injektion verschiedener Hormone

Some steroid hormones as well as clomiphene have been administered to new-born rats (postnatally) or to pregnant rats (prenatally) in order to study the effect on the future gonadal function of the animals born before or after the injection. A single postnatal androgen injection in oily solution influences only the female function; estrogen or the combination of androgen and estrogen are effective in both sexes preventing the ovulation or damaging the testicles. If the hormone is administered in water instead of oil, several injections are necessary in order to obtain an effect. Only the aqueous solution of clomiphene produces a positive effect even given in a single injection. When a single postnatal injection is effective the same result can be obtained after prenatal administration but only following intraamniotic injection. Clomiphene is an exception to this rule; intraamniotic injection has no effect. These observations permit the following conclusions: 1. It is possible to influence the hypothalamus-hypophysis function not only in the first days of life but already in the prenatal period. 2. As androgen damages only the ovary, estrogen however the gonads of both sexes, the mechanisme of action can not be the same. Androgen alters the function of the sexual centres in the brain only in the female rat, estrogen paralyses this function in both sexes. 3. Prenatal injection of hormone is only effective if administered intraamniotically (eliminating in this way the action of the placenta). This proves the important role of the placenta in the metabolisme of the hormones. 4. Other possible consequences of postnatal androgen administration as permanent obstruction of the vagina or hypertrophy of the clitoris can be obtained equally by prenatal intraamniotic injection. These phenomena can also occur independent of the avarian processes, being due to direct hormonal action. 5. Tubo-ovarian inflammation and abscesses are observed with relative frequency especially following estrogen or clomiphene-administration. The cause is unknown but we can assume that circulatory disorders in the genital area, produced by the hormone, are responsible for the frequency of these phenomena.

PIP: Several studies researching the effect of hormonal administration on the gonadal functions of rats are correlated. Hormonal preparations that are administered in oily solutions affect gonadal functions only if the injection is postnatal or intraamniotic. This indicates that the placenta plays an important role in maintaining a hormonal balance for the fetus after the mother receives extraamniotic, sc, or ip injections. Hormonal injections administered in water solutions must be repeated to have an effect. Clomiphene will affect gonadal functions when injected postnatally, but not when injected intraamniotically; experiments show that this is not due to any effect of amniotic fluid or clomiphene. Postnatal injection of testosterone affects only female animals, which would indicate a transformation of the biphasic function of the sexual centers of the cerebrum. Estradiol affects both sexes, which seems to result from a paralysis of the biphasal function. Intraamniotic injection of hormones or immediate postnatal injection of testosterone will hinder the opening of the vagina and cause hypertrophy of the clitoris, which will not always coincide with anovulatory ovaries. This would indicate different causes for these various dysfunctions. Inflammation of the adnexa uteri often accompanies hormonal injections (especially estrogen and clomiphene), which is probably linked to disturbances in the genital circulatory system.