Absence Of Ovaries Research Articles

Lactational control of reproduction.

In most mammalian species lactation suppresses fertility. There is no doubt that it is the suckling stimulus that provides the controlling signal, and, in human reproduction, this is the only truly physiological signal that suppresses fertility in normally nourished, healthy women. In breastfeeding women, the return of normal fertility follows a relatively well-defined path progressing through: an almost complete inhibition of gonadotrophin-releasing hormone/luteinizing hormone (GnRH/LH) pulsatile secretion in the early stages of lactation; return of erratic pulsatile secretion with some ovarian follicle development associated with increases in inhibin B and oestradiol; a resumption of apparently normal follicle growth associated with a normal increase in oestradiol, but often an absence of ovulation, or formation of an inadequate corpus luteum; and a return to normal ovulatory menstrual cycles. A key element in controlling the rate of this progression is the impact of the suckling stimulus on the GnRH pulse generator, a common feature of lactation in those species for which there is information. The variability in the duration of lactational amenorrhoea between women is related to the variation in the strength of the suckling stimulus, a unique situation between each mother and baby. Full breastfeeding can provide a reliable contraceptive effect in the first 6 to 9 months, but the precise mechanisms whereby the suckling stimulus affects GnRH pulsatile secretion remain unknown. Many studies on the hypothalamic pathways that might be involved in the translation of the neural suckling stimulus to suppression of hypothalamic GnRH secretion have been undertaken, principally in rats. In women, suckling increases the sensitivity of the hypothalamus to the negative feedback effect of oestradiol on suppressing the GnRH/LH pulse generator, a mechanism that appears to be common across species. In contrast, the role of prolactin in the control of GnRH appears to be species-dependent, with the importance varying from none to an important role in late or throughout lactation. In women, there is little evidence for a role of leptin, opioids or dopamine, although this may merely reflect the ethical dilemma of being able to give sufficient drug to test the system in the mother since these drugs will pass through the breast milk to the baby. Regardless of mechanism, practical guidelines for using breastfeeding as a natural contraceptive have been developed, which allows mothers to utilize the only natural suppressor of fertility in women as an effective means of spacing births.

The McCoy Female Sexuality Questionnaire

The McCoy Female Sexuality Questionnaire (MFSQ) was developed from the questionnaire used in a longitudinal study of the menopausal transition and designed to measure aspects of female sexuality likely to be affected by changing sex hormone levels. The original questionnaire was revised to insure that questions were easy to understand and that labels for the Likert scales described a continuum. The revised MFSQ contains 19 questions, 18 items using 7-point Likert scales with labels at the center and endpoints and one item requesting a frequency of activity. Seven studies involving both clinical and convenience samples and two with double blind randomized controlled trials used 7, 9, 10 or 17 MFSQ items and demonstrated acceptable reliability, internal consistency, apparent face and content validity as well as considerable evidence of construct validity. Results showed selected MFSQ item ratings decreased as women progressed through the menopausal transition, varied positively with endogenous estradiol and androgen levels, were higher in postmenopausal women receiving hormone replacement therapy (HRT), and differentiated between different types of oral contraceptives and the presence or absence of ovaries. Convergent validity was demonstrated for change in 9-item MFSQ score with change in psychological general well-being (PGWB) score and the Women's Health Questionnaire (WHQ) sex life subscale.

Ultrasonographic assessment of the ovarian response in eCG-treated goats

A study was conducted to evaluate the accuracy of ultrasonographic evaluation of ovulation rate during the early luteal phase of does and to estimate the reliability of ultrasonic scanning to differentiate between the corpus luteum and luteinized follicles. Both ultrasonographic and laparoscopic observations of ovarian structures and radioimmunoassays of progesterone in plasma were performed in 47 goats on day 7 after estrus synchronization using intravaginal FGA sponges and eCG. Ultrasonographic scanning allowed the determination of the presence or absence of ovulation. Total efficiency in detecting the occurrence of multiple ovulations was 87.5%. However, accuracy to establish the number of corpora lutea decreased to 23.5% in goats with three or more ovulations, due to an increasing underestimation as the number of corpora lutea in the ovary increased ( p<0.001). Ultrasonographic assessment of ovulation rate can be used to determine if a goat has ovulated or if multiple ovulations have occurred, but not to establish the precise number of corpora lutea. Evaluation of the ratio between cavity diameter and total luteal-tissue diameter is useful in distinguishing between corpora lutea and luteinized follicles, since the diameter differed between the two (0.36±0.21 vs. 0.64±0.16, respectively; p<0.005).

Effects of two monophasic oral contraceptives containing 150 mcg of desogestrel in combination with 20 or 30 mcg of ethinylestradiol on adolescent girls with oligomenorrhea and ovarian hyperandrogenism

Adolescent girls in the early years after their first menstruation are characterized by frequent irregular menstrual cycles and absence of ovulation, often associated with clinical signs of hyperandrogenism, including hirsutism and acne. Often in these adolescent girls, both the ovarian structure and endocrine characteristics do not allow to distinguish the disease from polycystic ovarian syndrome (PCOS) observed in adults.

New hyperprolactinemia and anovulation model in common marmoset ( Callithrix jacchus) and effect of cabergoline

We aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in common marmosets. The serum prolactin level gradually increased during the twice-daily administration of sulpiride and reached a plateau after 4 days. Sulpiride produced as big a response at 10 mg kg −1 as at 50 mg kg −1. In this study, the length of the ovarian cycle was approximately 30 days in normal common marmosets. Serum progesterone and estradiol levels showed no consistent change during the first 2 months of treatment with sulpiride. When treatment with sulpiride had been continued for more than 2 months, serum progesterone and estradiol levels fell to within the range seen in the follicular phase of the normal cycle and absence of ovulation was recognized by laparoscopy. A single oral administration of cabergoline (at doses between 0.01 and 0.1 mg kg −1) dose dependently reduced the elevated serum prolactin level. Bromocriptine (at an oral dose of 10 mg kg −1) also reduced the serum prolactin level at 4 and 8 h after its administration. With bromocriptine, the prolactin level had recovered at 24 h, but with cabergoline at doses of 0.05 mg kg −1 or more, it had still not recovered at 48 h. In anovulatory common marmosets, oral administration of cabergoline at a daily dose of 0.05 mg kg −1 restored ovarian function and resulted in ovulation in 100% of the group (following a reduction in the serum prolactin level). Bromocriptine at a daily oral dose of 10 mg kg −1 resulted in ovulation in 67% of the group, but this dose was about 200 times higher than the dose of cabergoline. We could produce an anovulatory model induced by sulpiride repeatedly administered over a long time period. It is suggested that, in this anovulatory model in common marmosets, cabergoline has a potent and long-lasting action as a dopamine D 2 receptor agonist, and thus could be a useful drug for the treatment of galactorrhea and hyperprolactinemic amenorrhea and/or anovulation.

Melatonin and the seasonal control of reproduction.

Many mammalian species from temperate latitudes exhibit seasonal variations in breeding activity which are controlled by the annual photoperiodic cycle. Photoperiodic information is conveyed through several neural relays from the retina to the pineal gland where the light signal is translated into a daily cycle of melatonin secretion: high at night, low in the day. The length of the nocturnal secretion of melatonin reflects the duration of the night and it regulates the pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Changes in GnRH release induce corresponding changes in luteinising hormone secretion which are responsible for the alternating presence or absence of ovulation in the female, and varying sperm production in the male. It is not yet known where and how this pineal indoleamine acts to exert this effect. Although melatonin binding sites are preferentially localised in the pars tuberalis (PT) of the adenohypophysis, the hypothalamus contains the physiological target sites of melatonin for its action on reproduction. Melatonin does not seem to act directly on GnRH neurons; rather it appears to involve a complex neural circuit of interneurons that includes at least dopaminergic, serotoninergic and excitatory aminoacidergic neurons.

Embryology and endocrinology of genital development

In the human male fetus, testes develop by the 7th week and begin to secrete two hormones: anti-müllerian hormone (AMH) induces the regression of müllerian ducts, the anlagen of the uterus, fallopian tubes and upper vagina, upon binding to a specific membrane receptor, whereas testosterone induces the differentiation of the wolffian ducts into the epididymes, vasa deferentia and seminal vesicles. In some target tissues, testosterone is converted to dihydrotestosterone, which is responsible for masculinization of the urogenital sinus and external genitalia. Both androgens act upon binding to the same nuclear receptor. In the absence of AMH and androgen action, or example in the female or in abnormal male differentiation, the internal and external genital primordia differentiate following the female pathway, even in the absence of ovaries. In males, an impaired function of the AMH-dependent pathway results in the persistent müllerian duct syndrome, a disorder characterized by the presence of uterus and fallopian tubes in otherwise normally virilized boys. Several mutations found in the AMH and AMH-receptor genes explain the pathophysiology of this syndrome.

Role of hormones in mammary cancer initiation and progression.

Breast cancer, the most frequent spontaneous malignancy diagnosed in women in the Western world, is a classical model of hormone dependent malignancy. There is substantial evidence that breast cancer risk is associated with prolonged exposure to female hormones, since early onset of menarche, late menopause, hormone replacement therapy and postmenopausal obesity are associated with greater cancer incidence. Among these hormonal influences a leading role is attributed to estrogens, either of ovarian or extra-ovarian origin, as supported by the observations that breast cancer does not develop in the absence of ovaries, ovariectomy causes regression of established malignancies, and in experimental animal models estrogens can induce mammary cancer. Estrogens induce in rodents a low incidence of mammary tumors after a long latency period, and only in the presence of an intact pituitary axis, with induction of pituitary hyperplasia or adenomas and hyperprolactinemia. Chemicals, radiation, viruses and genomic alterations have all been demonstrated to have a greater tumorigenic potential in rodents. Chemical carcinogens are used to generate the most widely studied rat models; in these models hormones act as promoters or inhibitors of the neoplastic process. The incidence and type of tumors elicited, however, are strongly influenced by host factors. The tumorigenic response is maximal when the carcinogen is administered to young and virgin intact animals in which the mammary gland is undifferentiated and highly proliferating. The atrophic mammary gland of hormonally-deprived ovariectomized or hypophysectomized animals does not respond to the carcinogenic stimulus. Administration of carcinogen to pregnant, parous or hormonally treated virgin rats, on the other hand, fails to elicit a tumorigenic response, a phenomenon attributed to the higher degree of differentiation of the mammary gland induced by the hormonal stimulation of pregnancy. In women a majority of breast cancers that are initially hormone dependent are manifested during the postmenopausal period. Estradiol plays a crucial role in their development and evolution. However, it is still unclear whether estrogens are carcinogenic to the human breast. The apparent carcinogenicity of estrogens is attributed to receptor-mediated stimulation of cellular proliferation. Increased proliferation could result in turn in accumulation of genetic damage and stimulation of the synthesis of growth factors that act on the mammary epithelial cells via an autocrine or paracrine loop. Alternatively estrogens may induce cell proliferation through negative feedback by removing the effect of one or several inhibitory factors present in the serum. Multidisciplinary studies are required for the elucidation of the mechanisms responsible for the initiation of breast cancer. Understanding of such mechanisms is indispensable for developing a rational basis for its prevention and control.

Control of pulsatile LH secretion during seasonal anoestrus in the ewe.

The seasonality of reproductive activity in the ewe in temperate latitudes is controlled by photoperiod. Its annual variations control the temporal organization of the sexual cycle by changing the activity of the gonadotrophic axis. Cyclic oestrous behaviour usually appears in the ewe at the end of summer or the beginning of autumn and finishes in winter or at the very beginning of spring. Seasonal anoestrus is characterized by the absence of ovulation and sexual behaviour. During seasonal anoestrus, a decrease in LH pulse frequency is observed. The inhibition of pulsatile LH secretion is maintained throughout the anoestrous season and is responsible for the low reproductive activity during this period. Variation in the seasonal inhibition of LH pulsatility results from an increase in the negative feedback by oestradiol on LH pulse frequency during the long days of spring and summer. The inhibition of LH secretion involves increased action of dopamine in the hypothalamus on the chain of nervous elements which controls gonadotrophic activity. Among the various dopaminergic structures, the retrochiasmatic A15 nucleus is involved in the inhibitory control of LH pulsatility by oestradiol during the long day period. Oestradiol increases the dopaminergic tone of the A15 nucleus in ovariectomized ewes during the long day period. In this structure, the effect of oestradiol on the dopaminergic metabolism probably results from a direct, local activation. In the sheep, dopamine might also participate in the inhibition of gonadotrophin activity during other periods of reproductive life.

Neuroendocrine mechanism of anovulation in users of contraceptive subdermal implant of nomegestrol acetate (Uniplant)

To evaluate a nomegestrol acetate subdermal contraceptive implant's (Uniplant; Thermex, Monaco) effect on the hypothalamus-pituitary-ovarian axis. A prospective clinical trial. San Borja-Arriarán Clinical Hospital, University of Chile, School of Medicine. Normally cycling healthy women. Insertion of Uniplant. Luteinizing hormone pulse and endocrine profiles were assessed before, 48 hours after insertion, and after prolonged use of the implant. Anovulation was noted in 100% of users in the first month. Seventy percent of subjects demonstrated follicular development with the absence of ovulation and an endocrine profile similar to the follicular phase: (LH pulse/8 hours 6.85 +/- 0.67, LH amplitude 3.54 +/- 0.65 mIU/mL (conversion factor to SI unit, 1.00), and E2 193 +/- 29.4 pg/mL (conversion factor to SI unit, 3.67), whereas 30% demonstrated no follicular activity with an endocrine profile similar to the luteal phase: (LH pulse/8 hours; 3.66 +/- 0.66, LH amplitude 5.76 +/- 1.73 mIU/mL, and E2 67.5 +/- 4 pg/mL. Clinical characteristics, serum gonadotropin concentration, and LH pulse characteristics failed to predict which subjects would initiate or remain devoid of follicular activity. Uniplant results in anovulation via two mechanisms: hypothalamic suppression in subjects who lack follicular development, and likely suppression of the pituitary LH surge in subjects who initiate follicular activity.

Experimental Analysis of Sexual Differentiation of the Zebra Finch Brain

Classical theories of sexual differentiation of brain and behavior hold that sex differences in the brain arise because of the action of gonadal steroid hormones. In mammals, testosterone secretion by the testes stimulates a masculine pattern of neural differentiation, whereas feminine patterns of development occur in the absence of testicular secretions. In some bird species, estrogen secreted by the ovary is thought to trigger feminine patterns of neural development, whereas masculine development occurs in the absence of ovaries. Sexual differentiation of the neural circuit for song in zebra finches is not easily explained by these theories. Although female zebra finches can be masculinized by treatments with estrogen, it has proven difficult to prevent masculine neural development in genetic males by treating them with inhibitors of estrogen synthesis. Moreover, when genetic female embryos are treated with inhibitors of estrogen synthesis, they develop significant amounts of testicular tissue that causes little or no masculinization of the song system. Thus, testicular secretions alone appear to be insufficient to cause masculine neural differentiation, and other factors need to be invoked. These factors may include ovarian secretions that inhibit masculine development, or direct genetic (nonhormonal) effects on neural differentiation.

Bilateral absence of ovaries in an XX-female; the ultimate form of XX-dysgenesis, or a separate entity?

Bilateral absence of ovaries in an XX-female; the ultimate form of XX-dysgenesis, or a separate entity?

Participation of the pineal gland in sexual maturation of female rainbow trout (Oncorhynchus mykiss Walbaum).

In the study rainbow trout, pinealectomized at two different periods of their sexual cycle, i.e., at either 1 or 5 months before spawning, were studied. It was found that the lack of the pineal gland in the period directly preceding the spawning had no statistical effect on either spawning or the number of females that produced eggs. Pinealectomy performed during vitellogenesis delayed spawning by about 2 weeks and resulted in the absence of ovulation in 20% of the females. The results suggest that the pineal gland may influence the hypothalamo-pituitary-gonadal axis by altering the maturation period and controlling spawning in the rainbow trout.

Seasonal changes of gonadotropin-releasing hormone secretion in the ewe.

A sustained volley of high-frequency pulses of GnRH secretion is a fundamental step in the sequence of neuroendocrine events leading to ovulation during the breeding season of sheep. In the present study, the pattern of GnRH secretion into pituitary portal blood was examined in ewes during both the breeding and anestrous seasons, with a focus on determining whether the absence of ovulation during the nonbreeding season is associated with the lack of a sustained increase in pulsatile GnRH release. During the breeding season, separate groups (n = 5) of ovary-intact ewes were sampled during the midluteal phase of the estrous cycle and following the withdrawal of progesterone (removal of progesterone implants) to synchronize onset of the follicular phase. During the nonbreeding season, another two groups (n = 5) were sampled either in the absence of hormonal treatments or following withdrawal of progesterone. Pituitary portal and jugular blood for measurement of GnRH and LH, respectively, were sampled every 10 min for 6 h during the breeding season or for 12 h in anestrus. During the breeding season, mean frequency of episodic GnRH release was 1.4 pulses/6 h in luteal-phase ewes; frequency increased to 7.8 pulses/6 h during the follicular phase (following progesterone withdrawal). In marked contrast, GnRH pulse frequency was low (mean less than 1 pulse/6 h) in both groups of anestrous ewes (untreated and following progesterone withdrawal), but GnRH pulse amplitude exceeded that in both luteal and follicular phases of the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Glomemlonephritis Associated with Robertsonian Translocation t(13;14)

We report the first case of glomerulonephritis associated with Robertsonian translocation t(13;14) in a 18-year-old female. The renal biopsy revealed mesangial proliferative glomerulonephritis with mesangial IgG and C3 deposits. The patient also has congenital absence of ovaries and an underdeveloped uterus. Our report suggests that renal abnormalities may be found in patients with Robertsonian translocation.

Inhibin secretion after treatment with an LHRH agonist and subsequent ovarian hyperstimulation induced by FSH in the macaque (Macaca arctoides)

The effect of ovarian hyperstimulation with 'pure' FSH on serum concentrations of immunoreactive inhibin in macaques in which endogenous gonadotrophin secretion and ovarian activity had been suppressed by an LHRH agonist implant was studied. Four stump-tailed macaques were treated with an LHRH agonist implant in the early follicular phase of the cycle. After a transient stimulatory phase oestradiol secretion was markedly suppressed, and the rises in progesterone and inhibin observed after ovulation were absent. At 8 weeks after implant administration, when serum LH was only just detectable, FSH (Metrodin) was administered to the LHRH agonist-treated macaques once daily for 9 days (75 i.u. on Day 0, 35 i.u. Days 1-8). FSH treatment stimulated a marked increase in oestradiol and immunoreactive inhibin secretion in the absence of a rise in serum progesterone concentrations. Comparison of the FSH-induced pattern of inhibin secretion with the profile during the normal menstrual cycle showed that during the normal cycle inhibin is secreted into the peripheral blood almost exclusively during the luteal phase in the macaque, but stimulation of follicular development by exogenous FSH was associated with a rise in inhibin concentrations in the absence of ovulation. These results suggest that this non-physiological rise in inhibin may be one of the factors involved in the changes in endogenous gonadotrophin secretion which can occur during ovarian hyperstimulation.

Placental production of estradiol and progesterone after oocyte donation in patients with primary ovarian failure

After oocyte donation 18 pregnancies were established in 17 patients with the absence of ovaries. Eight patients were delivered of nine healthy infants including one set of twins, six pregnancies were progressing normally, and four pregnancies were aborted. Four pregnancies were established after transfer of frozen-thawed embryos. In the simulated luteal phases, replaced with estradiol valerate and progesterone, pregnancies could be established and maintained as indicated by the profile of serum human chorionic gonadotropin concentrations. Weekly determinations of serum 17 beta-estradiol levels indicated significantly higher values at 7 weeks' gestation, as compared with week 5. This observation precludes that the luteoplacental shift occurred before 7 weeks' gestation. The weekly serum determinations of progesterone were significantly higher week 9, as compared with week 5. Two pregnancies were achieved after the vaginal administration of micronized progesterone.

Modification of symptoms of the premenstrual syndrome during ovarian suppression with goserelin (Zoladex) depot – potential for research and clinical investigation

Eleven women with premenstrual problems were treated in an open study for up to 6 months with goserelin (Zoladex) 3.6mg by monthly subcutaneous depot. Twice weekly assay of urinary estronc glucuronide and pregnanediol demonstrated absence of ovulation and suppression of estrogen excretion to within or below the early follicular phase range. Physical and psychological symptoms, measured by daily self assessment, were significantly improved during therapy. However, some subjects continued to record intermittent episodes of swelling and adverse mood in the absence of changes in ovarian activity. Three women reported marked but transient worsening of anxiety and/or depression soon after the onset of ovarian suppression, one later withdrawing from the study. Return of ovulatory menstruation was preceded by recurrence of symptoms at pretreatment levels, although breast discomfort which was consistently improved during therapy showed a more sustained improvement. Although conclusions are limited by the lack of a...

The effect of estradiol valerate and allylestrenol on endometrial transformation in hypergonadotropic hypogonadic women

The effect of estradiol valerate and allylestrenol on the endometrial transformation of five hypergonadotropic hypogonadic women was evaluated. Estradiol valerate was administered throughout the whole induced cycle (28 days), while allylestrenol was added during the second half of the cycle. Endometrial biopsies were performed during allylestrenol treatment and were evaluated histologically. Samples of endometrium were also subjected to one-dimensional SDS electrophoresis. Of ten biopsies performed, only one was interpreted to be in-phase, while the others were dated proliferative (4 biopsies) or showed abortive or out-of-phase secretory transformation. The highest mean serum progesterone level, detected under allylestrenol treatment, was 1.5 ng/ml. Protein electrophoresis demonstrated relative sequential changes in the protein patterns of the 115 kDa and 150 kDa protein bands. It is concluded that allylestrenol, although having gestagen properties, may not be efficient for the induction of an adequate secretory transformation of human endometrium in the absence of ovaries.

Effects of suckling and low doses of estradiol on luteinizing hormone secretion during the postpartum period in beef cows

An experiment was conducted to test if suckling acutely suppressed circulating levels of LH during the postpartum period in beef cows. In addition, the influence of exogenous administration of low concentrations of estradiol on LH secretion during the postpartum period was evaluated. Twelve mature cows were randomly assigned before parturition to one of three treatments. Four intact cows were used as controls (INT). Eight cows were ovariectomized within the first 7 days following parturition. Four of these cows received a silastic 17β-estradiol implant subcutaneously at the time of ovariectomy (OVX-E); the remaining four cows received no further treatment (OVX). All cows were allowed to nurse one calf for 30 min daily between 1200 and 1230 hours for the duration of the experiment. Blood samples were collected at 12 min intervals for 6 hr before and 6 hr after suckling on days 9, 30, 44 and 58 postpartum. Mean interval (mean ± SE) to the first increase in peripheral progesterone concentrations indicative of the onset of ovarian luteal activity was detected in INT cows 37 ± 4.9 days postpartum. An acute effect of suckling on LH secretion did not occur in INT and OVX cows but mean LH concentrations were reduced in OVX-E cows following suckling on days 44 and 58. Mean LH concentrations remained low in INT cows; whereas, in OVX and OVX-E cows LH concentrations increased linearly (P<0.05) as the interval from time of ovariectomy increased. Cows in the OVX-E group had a higher mean concentration of LH than cows in the OVX group at 30, 44 and 58 days postpartum (P<0.05). Frequency of LH pulses did not differ between cows in the OVX and OVX-E groups at any period. Data from this experiment support the concept that suckling is acting in a chronic fashion to inhibit LH secretion during the postpartum period. In the absence of ovaries, chronic administration of exogenous estradiol in low concentrations has a positive effect on secretion of LH in the postpartum cow.