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PubMedDate not supplied

Exogenous gonadotropin therapy in combined anovulatory and male factor infertility.

This retrospective study evaluated conception rates in 18 women with refractory anovulatory infertility undergoing hMG ovulation induction in the presence of persistent mild to moderate semen abnormalities. Logistic regression analysis showed no relationship between conception (9.6% cycle) and the age of either partner, primary versus secondary infertility, or lowest sperm count, motility or morphology. In summary, this study demonstrates that a coexisting mild to moderate male factor does not preclude pregnancy during hMG therapy for anovulation. While semen abnormalities should not be ignored, aggressive treatment of concomitant ovulatory disorders and the resulting timed ovulation of several oocytes may minimize the effects of semen abnormalities.

Adult↗
PubMed1997

[Gonadal dysfunction].

Function of hypothalamic-pituitary-ovarian axis is an essential factor for the maintenance of regular cycles in mature women. The disturbance of function of those organs causes gonadal dysfunction such as anovulation, amenorrhea and menstrual disorders. Therefore, the correct diagnosis for the assessment of CNS and ovarian function is clinically important to treat the patients those who have an menstrual disorders. In this review, the mechanism of normal gonadal cycles and the diagnostic method and the treatment of gonadal dysfunction are described.

Amenorrhea↗
PubMed1997

[Female sterility].

Recent progress in female sterility of Japanese women is reported in this study. The causes of sterility in the female side, the most popular sterile factor is a tubal factor due to the increase of the endometriosis and pelvic inflammatory disease. The main treatment of the tubal factor is an IVF-ET technique. The ovulatory disturbances occupy the second position of the female sterile factor. The precise endocrinological examinations must be done for the diagnosis of the ovulatory disturbances. In case of the hypergonadotropic hypogonadism, the ovulation induction is almost impossible. Generally, clomiphene citrate is used for moderate hypothalamic anovulations, and bromocriptine or terguride is for prolactin related diseases (hyperprolactinemia, occult hyperprolactinemia, galactorrhea) and endocrinological PCO (LH/FSH > 1) in the beginning. If these treatments are not effective, hMG-hCG therapy will be performed. During hMG-hCG therapy, we must take care for the occurrence of the ovarian hyperstimulation syndrome. For the treatment toward the cervical factor, the artificial insemination with husband semen will be done, however, if it is not effective, IVF-ET must be performed. For the uterine factor (such as after hysterectomy state, adhesion of uterine cavity, etc.) surrogate mothers are hired in some foreign countries, however, it is prohibited in Japan. If patients have anti-phospholipid antibodies, low dose aspirin and/or heparin administration will be done for the treatment of infertility. Recently, the assisted reproductive technology (ART) have made much progress. IVF-ET is performed widely in Japan. Cryopreservation of the fertilized ovum and intracytoplasmic sperm injection (ICSI) are also performed. However, the legal and ethical problems are occurring, and much discussion must be done for the acceptance of such new technologies.

Anovulation↗
PubMed1976

Hormonal findings associated with aluteal cycles.

Menstrual bleeding with no detectable luteal function was observed cyclicly in 3 infertile patients. Anovulation was suspected and documented by basal body temperature charts and repeated endometrial biopsies prior to expected menses. A sporadic anovulatory cycle in a normally ovulating volunteer was studied and the hormonal parameters included for comparison. To elucidate the significance and the possible cause of this defect, five aluteal cycles were evaluated with serum follicle stimulating hormone (FSH), luteinizing hormone (LH), total estrogen, progestin, and prolactin determinations. No similar patterns of FSH, LH, or estrogen values were observed. No abnormality of prolactin levels was noted. The lack of progestin rise and proliferative endometrial biopsies during the second half of these cycles were the only consistent findings. When clomiphene citrate therapy was instituted, a luteal phase was promptly established.

Adult↗
PubMed2006

Longitudinal study on the role of body size in premenopausal breast cancer.

BACKGROUND: A high body mass index (BMI) has been related to a reduced risk of breast cancer in premenopausal women. The mechanisms underlying this association have not been elucidated. METHODS: We explored whether factors affecting ovulation may explain the inverse association between BMI (calculated as weight in kilograms divided by the square of height in meters) and breast cancer in 113,130 premenopausal participants in the Nurses' Health Study II. During 1,225,520 person-years of prospective follow-up between 1989 and 2003, 1398 incident cases of invasive breast cancer were diagnosed. Weight, height, ovulatory infertility, menstrual cycle patterns, and a multitude of covariates were assessed throughout follow-up. Cox proportional hazards regression was used to compute hazard ratios and 95% confidence intervals (CIs). RESULTS: We observed a significant linear inverse trend between current BMI and breast cancer incidence (P<.001) that was not explained by menstrual cycle characteristics or infertility due to an ovulatory disorder (covariate-adjusted hazard ratio for breast cancer in women with a BMI > or =30 vs 20.0-22.4, 0.81; 95% CI, 0.68-0.96). We found BMI at age 18 years to be the strongest predictor of breast cancer incidence (covariate-adjusted hazard ratio for breast cancer in women with a BMI at age 18 years > or =27.5 vs 20.0-22.4, 0.57; 95% CI, 0.41-0.81). CONCLUSIONS: Body size during the early phases of adult life seems to be particularly important in the development of premenopausal breast cancer. Factors other than anovulation are likely to mediate the protection conferred by a high BMI.

Adult↗
PubMed1999

Intrauterine exposure to clomiphene and neonatal persistent hyperplastic primary vitreous.

A 4-year-and-10-month-old girl was diagnosed shortly after birth with persistent hyperplastic primary vitreous (PHPV). Her mother took clomiphene 100 mg daily for approximately 4 weeks and discontinued the drug once she had a positive pregnancy test. The exact time of gestation was not clear. Clomiphene is an estrogen antagonist effective in the treatment of anovulation. Various ocular side effects have been described in women taking the drug, including decreased vision, mydriasis, flashing lights, central scotoma, photophobia, diplopia, allergic reactions, retinal vasospasms, detachment posterior vitreous, and possibly posterior subcapsular cataracts. These occur in 1.5-10% of patients taking clomiphene. The potential effects of clomiphene on the fetus have been investigated in five animal studies. Cataracts were observed in fetal mice and rats, but not in monkeys. In humans, a case of congenital retinal aplasia was described. The possibility of clomiphene-induced congenital PHPV should be considered, especially in pregnant women who are taking a high and prolonged dose.

Animals↗
PubMed1999

Reproductive biology of female titi monkeys (Callicebus moloch) in captivity.

Titi monkeys (Callicebus spp., Cebidae) are monogamous neotropical primates that live in family-like groups typically consisting of an adult monogamous pair and one or two young. Knowledge about the reproductive biology of this genus is scanty. This study investigated the reproductive biology of female dusky titi monkeys (Callicebus moloch). An initial analysis characterized reproductive parameters of 32 females from a captive colony maintained for 23 years at the California Regional Primate Research Center (CRPRC). The colony records provided data on reproductive parameters such as interbirth intervals, seasonality, age at first pregnancy, and reproductive rate in captivity. Changes in urinary levels of estrone conjugates (E1C) and pregnanediol-3alpha-glucuronide (PdG) were used to characterize major reproductive events. Urine samples from eleven females were collected during 17 months. The endocrine data were used to examine changes associated with cycling, conception, and the post-partum period as well as to determine the duration of the ovarian cycle and gestation length. The analysis of colony records indicated that females whose infant survived through weaning gave birth at intervals remarkably close to one year, while those who lost their offspring showed a significantly shorter interval. As long as they lived within the family group, mature female offspring did not breed. The analysis of the endocrine profiles indicated that after giving birth to a viable offspring, females undergo a relatively prolonged period of anovulation (approx. 6.5 months), followed by 1-3 non-conceptive cycles (approx. 1 month), after which they conceive and gestate (4.3 months).

Animals↗
PubMed2000

Induction of ovulation by clomiphene citrate in the Indian vespertilionid bat, Scotophilus heathi.

The ovulation induction property of clomiphene citrate (CC) and human chorionic gonadotropin (hCG) was studied in Scotophilius heathi, an Indian tropical vespertilionid bat, during the period of delayed ovulation between December to early January. The results of the study showed that 10 microg of CC alone was ineffective to induce ovulation, whereas 100 microg CC and 10 IU hCG alone induced ovulation. A significant (P < 0.01) increase in the ovulation rate was observed when 10 microg CC followed by 10 IU hCG, compared to 10 IU hCG and 100 microg CC alone groups. Finally, CC at a 100 microg dose, followed by 10 IU hCG, produced superovulation (14.00 +/- 0. 70), which is significantly different in comparison to all other groups. This is the first report of ovulation induced by CC in the Indian tropical bat as well as in any animal model that exhibits temporary anovulation similar to polycystic ovary syndrome (PCOD) during the normal physiology of reproduction.

Animals↗
PubMed1981

Estrogen--a cause of gynecologic cancer?

For many years before the first case-control studies showing an increased risk of endometrial cancer among menopausal estrogen users were published, a considerable body of circumstantial evidence accumulated suggesting a tumor-promoting role for estrogens in specific target organs. In regard to endometrial cancer, an "estrogen hypothesis" has evolved based on observations such as an increased incidence of endometrial cancer in patients with chronic anovulation and in patients with estrogen-secreting ovarian tumors; development of endometrial cancer in certain estrogen treated animals; and successful treatment of some metastatic endometrial cancer with progesterone. Since 1975, a number of case-control studies have appeared relating estrogen treatment of menopausal women to a rising incidence of endometrial cancer. The same cannot be said, with a few exceptions, of studies of breast and ovarian cancer. An understanding of the physiology of the estrogens, particularly in obese women, aids in understanding the possible role of estrogen in promoting endometrial neoplasia. Although the case for estrogens promoting some forms of endometrial cancer is strong, at the present time it cannot unequivocally be stated that estrogens cause any form of cancer in humans.

Carcinogens↗
PubMed1984

The effect of westernization on urine estrogens, frequency of ovulation, and breast cancer risk. A study of ethnic Chinese women in the Orient and the USA.

In a 10-year incidence survey of breast cancer in the City of Boston, 14 cases in American Chinese women were observed, while approximately 13 were expected on the basis of age-specific incidence in the white population. In Hawaii, on the other hand, while breast cancer incidence rates for ethnic Chinese are approximately three times as high as those of indigenous Chinese populations, data indicate that they are still 35% lower than those of whites in Hawaii or on the US mainland. We have compared estrogen concentrations in the urine of Chinese women in the Orient, Honolulu, and Boston. Levels of estrone (E1) and estradiol (E2) increased greatly from the low to the high risk group. The increase was evident among both the younger (15-19 years) and the older (20-24 years) women, in both follicular and luteal phase specimens. The crude unweighted average increase from Oriental to continental US Chinese was about 38% and 34% for E1 and E2, respectively. On the other hand, levels of E3 decreased from the low-risk to the high-risk group, but the decrease was modest (16%) and not always regular. There were no systematic or significant differences in the frequency of ovulation in the three groups of women. These results are compatible with the hypothesis that high levels of estrone and estradiol are important to breast carcinogenesis. Whether E3 has some additional "protective" effect or is irrelevant is unclear. The data do not support the hypothesis that total urine estrogens (E1 + E2 + E3) are predictive of population groups at high risk for breast cancer and they appear inconsistent with the hypothesis that frequency of ovulation (or anovulation) is an important aspect of breast carcinogenesis.

Adolescent↗
PubMed1992

Cystogenesis of the ovarian antral follicle of the rat: ultrastructural changes and hormonal profile following the administration of dehydroepiandrosterone.

Immature 27-day-old female Sprague-Dawley rats were administered daily subcutaneous injections of dehydroepiandrosterone (DHEA, 5 mg/100 g BW) to induce the formation of ovarian follicular cysts. Groups of rats were killed on days 0, 10, 15, 20, 25, and 30. Ovaries from each group of rats were processed for light and electron microscopy and for follicular or cystic fluid hormone analysis. Normal antral follicle fluid, PMSG-treated preovulatory follicular fluid, and cystic fluids were analyzed for progesterone (P), estrone (E1), estradiol (E2), testosterone (T), delta 4-androstenedione (delta 4-A), 5 alpha-dihydrotestosterone (DHT), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL). DHEA induced anovulation, acyclicity, and the formation of follicular cysts. In certain antral follicles, there was a dramatic increase in the quantities of smooth endoplasmic reticulum (SER) in the granulosa cells and many mitochondria had tubular cristae. Further depletion of granulosa cell number was associated with intense blebbing of the cytoplasm into the follicle antrum. Formation of the ovarian follicular cyst was completed when the entire cyst was lined by a single layer of transformed granulosa cells in contact via adhering, gap, and tight junctions. These cells had little cytoplasm, mitochondria with lamellar cristae, vast basal and apical bands of microfilaments, and an extensive array of smooth-surfaced endocytotic invaginations on the basal plasma membrane. These endocytotic pits may subsequently form smooth-surfaced vesicles and thereby serve as one mechanism for moving fluid from the ovarian interstitium into the cyst. Theca interna cells were rarely observed in the peripheral regions of the cyst. Abundant smooth muscle cells were located beneath the basement membrane of the epithelial cells comprising the cyst wall. These acquired morphological and physiological features may ensure persistence of the ovarian cyst and thus potentiate a chronic pathological condition. In this study it was also shown that progesterone, estrone, and estradiol as well as androgen concentration increased in the follicle after PMSG treatment. With DHEA treatment, the follicular cystic fluid concentrations of these steroids progressively increased to extremely high levels concurrent with the development of the follicular cysts.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Gomori-positive astrocytes: biological properties and implications for neurologic and neuroendocrine disorders.

Granule laden astrocytes exhibiting an affinity for chrome alum hematoxylin and aldehyde fuchsin (Gomori stains) have been described in the periventricular brain of all terrestrial vertebrate species examined to date including humans. The astrocytic inclusions are rich in sulfhydryl groups, emit an orange-red autofluorescence, and stain intensely with diaminobenzidine, a marker of endogenous peroxidase activity. The distinct autofluorescence pattern and the absence of neutral lipid, acid phosphatase, and beta-glucuronidase activity exclude lipofuscin or lysosomes as components of these astrocytic granules. The emission of orange-red autofluorescence and the nonenzymatic nature of the peroxidase activity implicate the presence of porphyrins and metalloporphyrins such as heme as major constituents of these cytoplasmic gliosomes. The role of Gomori-positive astrocytes under normal and pathologic conditions is incompletely understood. In vivo, numbers of astrocytic granules increase as a function of advancing age, in response to chronic estrogen stimulation, and following X-irradiation. In vitro, these cells accumulate with increasing time in culture and following exposure to the sulfhydryl agent, cysteamine. Gomori-positive astrocytes may supply heme to neurons for the synthesis of cytochromes, catalases, and other heme enzymes. They may play a role in photostimulation of sexual cyclicity, the promotion of neuritic development, the degradation of toxic lipoperoxides, and the metabolism of various neurotransmitters. Conversely, these cells may contribute to the pathogenesis of several neurologic and neuroendocrine disorders. Examples of the latter include a) augmentation of goldthioglucose neurotoxicity, b) induction of hypothalamic anovulation and reproductive failure, c) exacerbation of porphyric encephalopathy, and d) potentiation of parkinsonism and other free radical-related neurodegenerations.

Animals↗
PubMedDate not supplied

Endocrine effects of oral contraception.

Numerous well-documented endocrine effects of oral contraceptives (OCs) can be subdivided into two groups: (a) those relating to the hypothalamic and pituitary-ovarian system, the breast and the genital tract of the human female and (b) those related indirectly to laboratory testing of other endocrine glands. Benefits from OC use include marked decreases in the incidence of menorrhagia, benign breast disease, dysmenorrhea, iron deficiency anemia, premenstrual tension and ovarian cyst formation--all of which will be discussed only briefly. Of much concern are two suggested adverse effects of OCs: (a) the development of amenorrhea or menstrual disturbance associated with anovulation after discontinuing OCs, thereby possibly influencing the future fertility of former OC users, and (b) the suggested relationship between hyperprolactinemia and the development of micro- and eventually macropituitary adenomas. A review of the literature, along with our own findings, is presented.

Adenoma↗
PubMed2000

Endometrial intraepithelial neoplasia (EIN): will it bring order to chaos? The Endometrial Collaborative Group.

The diagnosis of precancerous lesions of the endometrium remains unstandardized because existing World Health Organization classification categories do not correspond to distinctive biologic groups and are inadequately supported by reproducible histopathologic criteria. A group of gynecologic pathologists was convened to consider revised diagnostic classification and criteria based on newly available information. We propose the terms endometrial hyperplasia (EH), endometrial intraepithelial neoplasia (EIN), and adenocarcinoma to define distinctive subgroups that are functionally relevant to clinical management of patients with endometrial disease. Endometrial precancers are collectively designated EIN in recognition of their monoclonal growth. At present there is no effective strategy for constructive subdivision of EIN lesions into grades or subgroups. EIN is to be distinguished from adenocarcinoma and the diffuse hormonal changes of EH seen in anovulation. An archive of genetically and morphologically classified endometrial precancers at www.endometrium.org provides a resource for centralized review of the histopathology of EIN lesions. A new architectural criterion for EIN diagnosis, diminution of stromal volume to less than approximately half of the total sample volume, will also assist in discriminating between EH and EIN. Implementation of this proposal will bring diagnostic terminology into agreement with current concepts of premalignant endometrial disease and facilitate more uniform patient management.

Adenocarcinoma↗
PubMed1997

Social and developmental influences on reproductive function in female Wied's black tufted-ear marmosets (Callithrix kuhli).

Although marmoset social groups may contain multiple adult females, reproduction is typically limited to one breeding female. A variety of endocrine and behavioral mechanisms have been identified that regulate fertility among female marmosets. In the present study, we assessed the mechanism(s) by which fertility is regulated in female black tufted-ear marmosets, Callithrix kuhli. The reproductive status of 10 daughters aged 2-24 months was evaluated by measuring concentrations of urinary pregnane-diol 3 alpha glucuronide (PdG) and luteinizing hormone (LH). Concentrations of the two hormones were typically low in daughters less than 12 months of age, and the profiles suggested anovulation (mean PdG < 2 micrograms/mg Cr and mean LH < 6 ng/mg Cr). Concentrations of PdG rose dramatically in females older than 12 months. Eight subadult daughters commenced ovulatory function while still living with their family, and the remaining two failed to ovulate. The onset of ovarian function coincided with a change in the social environment in two females, but the remaining six females commenced spontaneous ovarian activity that was not associated with any social or environmental factor (mean age: 15.6 +/- 1.6 months). Ovulatory function was monitored in five daughters while housed in their natal family group, while removed from the natal family group and housed singly, and while paired with an unrelated and unfamiliar male. The ovarian cycles of these females housed in the natal group were characterized by significantly shorter luteal phases and reduced PdG concentrations, relative to when the females were housed on their own, and relative to adult breeding females (n = 6). Stimulatory cues from unfamiliar males were not necessary to trigger regular ovarian function in females. In this species, the regulation of fertility in daughters is a complex combination of behavioral and endocrine factors.

Animals↗
PubMed1998

Suppression of cortisol levels in subordinate female marmosets: reproductive and social contributions.

Socially subordinate female common marmosets (Callithrix jacchus) have markedly lower plasma cortisol levels than dominant females. Subordinate females also undergo hypoestrogenemic anovulation, and estrogen can elevate glucocorticoid levels. Therefore, we previously hypothesized that this cortisol difference is mediated by rank-related differences in reproductive hormones, probably estradiol. To test this possibility, we characterized the effects of the ovarian cycle and ovariectomy on plasma cortisol concentrations. Beginning in the early follicular phase, basal blood samples were collected from seven cycling female marmosets daily for 16 days and at 2- to 3-day intervals for another 16 days. Samples were collected identically from seven anovulatory subordinate females and seven long-term ovariectomized females. Cortisol levels changed reliably across the ovarian cycle, with levels in the mid- to late follicular, peri-ovulatory, and early luteal phases higher than those in the remainder of the cycle. Cortisol levels of cycling females were significantly higher than those of subordinates at all parts of the cycle, but were significantly higher than those of ovariectomized females only during the midcycle elevation. Unexpectedly, subordinates had significantly lower cortisol levels than ovariectomized females, as well as higher estradiol and estrone levels and lower progesterone and luteinizing hormone (LH) levels. These results confirm that circulating cortisol concentrations are modulated by reproductive function in female marmosets but also indicate that low cortisol levels in subordinate females cannot be attributed simply to hypoestrogenemia. Instead, other factors, such as direct effects of social subordination or suppression of LH levels, contribute to suppression of cortisol in subordinates.

Animals↗
PubMed2000

Cyproterone acetate and reversal of the impaired endometrial decidualization in streptozotocin-diabetic pseudopregnant rats.

Reproductive dysfunction in the female diabetic rat is associated with impaired hypothalamic-hypophyseal system, anovulation, insufficiency of ovarian steroidogenesis and spontaneous failure of pregnancy. Formation of decidua, the highly modified endometrium of pregnancy and pseudopregnancy could only be achieved when the uterus was sensitized by a sequence of oestrogen and progesterone. In this study, we examined whether the impaired expression of endometrial decidualization in the pseudopregnant rat is linked with diabetes-associated hypersecretion of testosterone. Rats were made pseudopregnant by sterile mating. Diabetes was induced by streptozotocin on day 1 p.c. Deciduogenic stimulus was given on day 5 p.c. Treatment of cyproterone acetate (10 mg kg(-1)) was scheduled from day 5 through day 9 p.c. Animals were killed on day 10 p.c, and the degree of endometrial decidual growth, plasma levels of oestradiol, progesterone, ACTH and testosterone were determined. Results showed that compared to controls there was a concomitant drop in endometrial decidual growth concurrently with impaired levels of oestradiol and progesterone in diabetic pseudopregnant rats. ACTH and testosterone levels were, however, profoundly elevated. Cyproterone acetate treatment in the diabetic pseudopregnant rat resulted in a simultaneous elevation of oestradiol and progesterone, which eventually helped the endometrial differentiation to decidua in the diabetic pseudopregnant rat parallel to controls. Present experimental data suggest that diabetes-associated impaired endometrial decidualization in the pseudopregnant rat is possibly caused by testosterone-induced oestrogen deficiency.

Adrenocorticotropic Hormone↗
PubMed2000

Irreversible effects of neonatal exposure to p-tert-octylphenol on the reproductive tract in female rats.

It has been known for many years that administration of androgens or estrogens at critical periods of development in mammals causes severe long-term effects on the endocrine/genital systems. The environmental pollutant p-tert-octylphenol (OP) possesses a weak but clear estrogen agonist activity in in vitro and in vivo studies. In the present study, effects of neonatal exposure to OP on the reproductive tract of female rats were investigated. Newborn female pups were injected with 100 mg/kg OP subcutaneously within 24 h after birth. Administration was repeated every other day until postnatal day 15 (total of eight doses). Before weaning, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) remained at low levels during OP exposure, although the serum FSH peak and the high LH level were obvious in the controls. Histologically, inhibition of uterine gland genesis was apparent. The day of vaginal opening was about 4 days earlier in OP-treated animals than in controls. Persistent estrus was consistently observed in OP-treated animals. Atrophic and polycystic ovaries without corpora lutea showed anovulation. In the endometrium, cell-proliferative activity and cell-death were increased and decreased, respectively, and expression of estrogen receptor alpha mRNA was apparent by in situ hybridization. Unexpectedly, endometrial hyperplasias appeared at 8 weeks of age. After ovariectomy, vaginal smears immediately became of castration type and the uterus was atrophied. These results suggested that neonatal exposure to a high dose of OP alters developmental hormonal secretion presumably due to a hypothalamo-pituitary-ovarian disorder, with accelerated vaginal opening, subsequent persistent estrus, and uterine endometrial hyperplasia. The changes in the uterus and vagina are ovary-dependent.

Animals↗