Inhibition of folliculogenesis in the monkey following early follicular phase administration of an LRH agonist

This study was undertaken to determine if early follicular phase administration of a synthetic luteinizing hormone releasing hormone (LRH) agonist would produce luteal phase defects in the monkey. [D-His(im-Bzl)6,Pro9]LRH N-ethylamide was administered to groups of rhesus monkeys on days 1-3 of the menstrual cycle. Two responses were observed: a) anovulatory menstrual cycles of less than 14 days duration, and b) ovulatory menstrual cycles characterized by unusually long follicular phases. All 4 monkeys with shortened menstrual cycles had prominent increases in serum gonadotrophin and oestradiol concentrations during treatment with the LRH agonist; early menses in these animals was attributed to uterine bleeding upon oestrogen withdrawal. Serum FSH concentrations declined, serum LH concentrations were unaltered, and only 2 of 8 monkeys had elevations in serum oestradiol during ovulatory menstrual cycles. The mean interval from cessation of treatment with the LRH agonist to the next preovulatory gonadotrophin surge was 21.5 +/- 3.2 days in ovulatory menstrual cycles. Corpus luteum function was normal following treatment with the LRH agonist in ovulatory cycles. The results indicate that both the long and short menstrual cycles observed following early follicular phase administration of the LRH agonist to monkeys can be attributed to a profound inhibition in follicle recruitment. [D-His(im-Bzl)6,Pro9]LRH N-ethylamide did not alter corpus luteum function in the monkeys.     

PLASMA TESTOSTERONE AND PROLACTIN IN THE MENSTRUAL CYCLE

Daily hormonal studies during nine ovulatory menstrual cycles showed that plasma prolactin and testosterone concentrations fluctuated randomly and independently. Mean plasma testosterone levels were found to be higher during the 7 days before and after the mid-cycle LH peak when compared to the premenstrual phase (P less than 0-01). No correlation was found between daily levels of prolactin and those of LH, FSH, oestrogen or progesterone and no correlation was seen between peaks of prolactin and testosterone or mean prolactin and testosterone levels. The lack of correlation between blood levels of prolactin and testosterone during the menstrual cycle suggests that prolactin is unlikely to have any direct controlling influence on the cyclical nature of testosterone production observed during ovulatory menstrual cycles.     

Pregnanediol excretion in fertile women: age-related changes

In normal women reproductive capacity diminishes with age; the decline has been detected before the start of the menopausal transition. It is known that in premenopausal women most menstrual cycles are ovulatory. An investigation was set up to examine the possibility that there is an age-related decline in the ability of the corpus luteum to secrete progesterone at this time. Once-weekly urine samples for the measurement of pregnanediol were collected from 100 women aged 20-48 years, all of whom had regular 20- to 35-day menstrual cycles (1124 samples collected during the course of 312 menstrual cycles of which 96.8% were ovulatory). Pregnanediol excretion rates parallel the levels of progesterone in plasma. Examination of the rank correlation between age and pregnanediol excretion identified a significant negative correlation during the early and mid-follicular phases, but failed to detect any age-related change during the luteal phase. The evidence does not support the concept of an age-related increase in luteal phase defects before the start of the menopausal transition.     

The menopausal transition: analysis of LH, FSH, estradiol, and progesterone concentrations during menstrual cycles of older women.

Studies of menstrual cycle length in large populations demonstrated that there is a striking increase in the variability of intermenstrual intervals just before menopause. The changes in serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) during menstrual cycles in a group of perimenopausal women were compared with the findings in young normal women. In 8 women, 46-56 years old with regular cycles, cycle length was shorter and the mean E2 concentration was lower than in younger women. There was a striking increase in FSH concentration throughout the cycle while LH remained in the normal range. In 2 women, 14 cycles of variable length were studied during 2 years of the menopausal transition. In some instances, hormonal changes associated with follicular maturation and corpus luteum function occurred in the presence of high, menopausal levels of LH and FSH with a diminished secretion of E2 and P. In others vaginal bleeding occurred during a fall in serum E2 with no associated rise in P. Cycles of variable length during the menopausal transition may be due either to irregular maturation of residual follicles with diminished responsiveness to gonadotropin stimulation, or to anovulatory vaginal bleeding that may follow estrogen withdrawal without evidence of corpus luteum function. The observation of elevated FSH concentrations and normal LH levels in perimenopausal women emphasizes the complexity of the hypothalamic-pituitary-ovarian regulatory system and suggests that LH and FSH are modulated independently at the level of the pituitary.     

The corpus luteum of the primate menstrual cycle is capable of recovering from a transient withdrawal of pituitary gonadotropin support

To further our understanding of the role of pituitary gonadotropin secretion in the control of corpus luteum function during the primate menstrual cycle, we have used an experimental model which enables us to directly control pituitary gonadotropin secretion throughout the luteal phase. Specifically, we have asked whether cessation of progesterone secretion, or functional luteolysis, resulting from a 3-day withdrawal of gonadotropin support, culminates in an irreversible loss of luteal responsiveness to further gonadotropic stimulation; and do the effects of gonadotropin deprivation vary with the age of the corpus luteum? Endogenous gonadotropin secretion was abolished in seven adult rhesus monkeys by placing radiofrequency lesions in the arcuate nucleus region of the medial basal hypothalamus. Endogenous gonadotropin secretion and ovulatory menstrual cycles were then restored by chronic pulsatile infusion of GnRH (1 pulse/h). Control luteal phases supported by this GnRH regimen exhibited typical plasma progesterone patterns and ranged from 14-17 days in length. In experimental cycles, endogenous gonadotropin secretion was interrupted for a 3-day period during the early (days 2-5), mid (days 8-11), or late (days 13-16) stages of the luteal phase. During the GnRH deprivation period, bioassayable and immunoreactive serum LH was undetectable. The disappearance of circulating LH was followed by a rapid fall in plasma progesterone levels regardless of the stage of the luteal phase. The restoration of gonadotropin secretion resulted in a resumption of progesterone secretion when the gonadotropin deprivation period was imposed during the early or midluteal phase. In each instance, the resumption of progesterone secretion continued for a period of time which effectively completed the typical 14- to 17-day functional lifespan of the corpus luteum of the menstrual cycle. Thus, the luteal phase was neither shortened nor lengthened by a 3-day interruption of luteal function resulting from withdrawal of gonadotropic support. When gonadotropin secretion was interrupted during the late luteal phase (days 13-16), restoration of gonadotropin secretion on day 16 did not result in resumption of progesterone secretion. Our findings confirm our earlier demonstration that progesterone secretion during the luteal phase of the non-fertile menstrual cycle is dependent on pituitary gonadotropic support.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of reduced luteinizing hormone concentrations on corpus luteum function during the menstrual cycle of rhesus monkeys

To further define the relationship between plasma LH concentrations and progesterone secretion by the primate corpus luteum, we examined luteal function in rhesus monkeys in response to reduced LH concentrations during the luteal phase of the menstrual cycle. Five anovulatory rhesus monkeys received a pulsatile infusion of synthetic GnRH (6 micrograms/pulse; one pulse per h, iv) to restore menstrual cyclicity. During the early luteal phase (4-5 days after ovulation), the amount of GnRH administered per pulse was reduced to 1/250th or 1/750th of the standard GnRH infusion regimen. Plasma LH concentrations, determined by bioassay, were reduced by approximately 50% during cycles maintained by reduced GnRH concentrations compared with the standard GnRH dosage. Serum progesterone concentrations were maintained for 5-6 days after GnRH reduction and declined thereafter, and premature menstruations were observed in four of seven cycles maintained by the 1/250th GnRH reduction and four of six cycles maintained with the 1/750th GnRH reduction. These results are consistent with the hypothesis that luteal regression during the nonfertile menstrual cycles of primates is due primarily to an alteration in luteal cell responsiveness to LH, rather than a reduction in the gonadotropic drive to the corpus luteum per se. When plasma LH concentrations were reduced during the early luteal phase to values below those found during the onset of luteal regression in control cycles, luteal function was maintained for 5-6 days. However, as the luteal phase progressed, the reduced LH concentrations were unable to sustain progesterone secretion, and premature menses occurred in some, but not all, animals.     

Endocrine and Metabolic Abnormalities in Adolescents with a PCOS-like Condition: Consequences for Adult Reproduction.

The polycystic ovary syndrome (PCOS) has a perimenarcheal onset. Increased luteinizing hormone (LH) and androgen concentrations are common among anovulatory adolescents and some also have hyperinsulinemia. Many will later have normal ovulatory cycles, whereas others with several co-existing abnormalities will develop full-blown PCOS with menstrual cycle irregularities and infertility in adulthood.     

Menstrual-Linked Asthma

This study was conducted to determine the occurrence of menstrual-linked asthma (MLA) in India in 100 consecutive female asthmatics in the reproductive age group. The patients were required to respond to a questionnaire concerning the relationship between their asthma and the menstrual cycle. Twenty-three patients had subjective perception of deterioration in symptoms of asthma in relation to the menstrual cycle. Ten patients from both groups were also required to maintain a daily peak expiratory flow rate (PEFR) diary for 2 consecutive menstrual cycles. The mean total duration of illness in patients with MLA was significantly longer than in patients without cyclic exacerbation. Cough and breathlessness were also significantly more severe as was the disease. This was evidenced by the more frequent emergency room visits and hospitalizations in these patients. Menstrual-linked worsening of asthma was most common in the premenstrual week (17 patients). In 8 of these 17 patients, this phenomenon continued to occur during the menstrual week also. Interestingly, 1 patient complained of deterioration of asthma 2 days after menstruation was over. Such an observation is yet to be recorded. Fourteen patients reported an increase in symptoms with almost every cycle while 3 had worsening related to specific season only. Sixteen patients often required extra medication during the premenstrual and/or menstrual weeks. A significant association was also observed between severity of premenstrual syndrome and MLA. The mean PEFR values over 2 cycles revealed a significant fall in the morning as well as evening values in the premenstrual and menstrual weeks as compared to the midcycle week in patients with MLA. This fall was maximal in the premenstrual week. Such a fall was not observed in asthmatics without menstrual exacerbation of symptoms. MLA was detected in about a fourth of the female asthmatics in India and it appears to represent a more severe form of the disease. This study also documented that MLA was associated with an increase in airway resistance and was not simply due to an increased perception of symptoms during the premenstrual or menstrual weeks.     

The menstrual cycle and its effect on inflammatory bowel disease and irritable bowel syndrome: a prevalence study

Objective: Female patients with bowel disease commonly report worsening symptoms in relation to the menstrual cycle. Our aim was to determine the nature of gastrointestinal symptoms correlating with the menstrual cycle in women with inflammatory and irritable bowel disease.
Methods: This was a retrospective study involving 49 women with ulcerative colitis (UC), 49 women with Crohn's disease (CD), 46 women with irritable bowel syndrome (IBS), and 90 healthy community controls. Participants were interviewed using a questionnaire including information regarding general health, medication history, pregnancy, as well as premenstrual and menstrual symptoms. χ² Testing and logistic regression modeling were used to test for differences in frequencies between groups and for risk analysis.
Results: Premenstrual symptoms were reported by 93% of all women but statistically more often by patients with CD (   p < 0.01  ). CD patients were also more likely to report increased gastrointestinal symptoms during menstruation (   p < 0.01  ), diarrhea being the symptom reported most often. All disease groups had a cyclical pattern to their bowel habits significantly more than controls (   p = 0.01  ). Cyclical symptoms included diarrhea, abdominal pain, and constipation. Logistic regression revealed an odds ratio (OR) of 1.1 (95% CI 0.9–1.2) for experiencing bowel symptoms during the premenstrual and menstrual phases and an OR of 2.0 (95% CI 1.2–3.2) for experiencing a cyclical pattern in bowel habit changes in women with bowel disease.
Conclusion: The prevalence of menstrually related symptoms is high, and appears to affect bowel patterns. The physiological and clinical effects of the menstrual cycle should be taken into consideration when assessing for disease activity.     

DOES TESTOSTERONE AFFECT THE NORMAL MENSTRUAL CYCLE?

In order to throw further light on the role of androgens in the aetiology of the polycystic ovary syndrome (PCO) we have examined the effect of artificially increasing serum testosterone levels on menstrual function in a group of ovulating women. Six women were studied who had either severe premenstrual syndrome or loss of libido for which they were treated with 100 mg testosterone by s.c. implantation. All had regular menstrual cycles. For 1 month before implantation serum LH, FSH, oestradiol (E2), progesterone and testosterone were measured three times per week. All women showed normal cyclical variation of LH, FSH, E2 and progesterone. Following implantation, three times weekly blood samples were taken during the first and third cycles. No patient had any disturbance of menstrual pattern. All continued to show cyclical changes of LH, FSH, E2 and progesterone. Serum E2 and progesterone were lower but not significantly so in the luteal phase of the treated cycles. This was despite a mean serum testosterone which rose from 1.3 to 7.1 nmol/l at the end of the third week following implantation and to 4.1 nmol/l at the end of the third month. Sex hormone binding globulin levels fell as expected by 18.5% during the first cycle. The lack of significant effect of a markedly elevated serum testosterone level on cyclical hormone changes is indirect evidence that in PCO the primary cause of the menstrual disturbance is not excessive production of ovarian or adrenal testosterone.     

Pituitary-ovarian relationships in polycystic ovary syndrome.

The spontaneous pattern of pituitary gonadotropins and ovarian steroids and their response to dynamic tests were measured in 12 women with polycystic ovarian syndrome (PCO) and the results compared to those from 6 normal women during the early follicllar phase of the cycle (controls). As judged by serial measurements of urinary total estrogen and pregnanediol over a 12-week period, in PCO patients 75% of cycles were anovulatory (anovulatory PCO) as compared to 100% ovulatory in controls. The basal concentrations of LH, androstenedione and estrone were significantly higher and the concentration os FSH significantly lower in anovulatory PCO than in the controls (P less than .05). In PCO patients the concentration of LH was lower following an ovulatory cycle than that following a period of anovulation. Negative and positive feedback responses to an estrogen provocation test (200 microgram ethinyl estradiol per day for 3 days) were normal in anovulatory PCO although the LH peak occurred 24 h earlier than in the controls. The amplitude of the pulses of LH was significantly greater in anovulatory PCO than in the controls and was suppressed in both groups after ethinyl estradiol. The peak release of LH in response to 56 microgram LRF in ovulatory PCO was similar in controls but LH responses in anovulatory PCO were significantly greater. It is suggested that the abnormalities in gonadotropin secretion in PCO are secondary to excessive and prolonged extraglandular production of estrogen from androstenedione.     

THE ROLE OF CHRONIC ANOVULATION IN THE POLYCYSTIC OVARY SYNDROME: NORMALIZATION OF SEX-HORMONE-BINDING GLOBULIN LEVELS AFTER CLOMIPHENE-INDUCED OVULATION

A group of anovulatory patients with polycystic ovaries (PCO) was given clomiphene citrate and compared with three control groups: normal women having spontaneous, ovulatory cycles, patients with PCO having spontaneous, regular, ovulatory cycles, and anovulatory patients without PCO. Comparisons were made at precise points of the menstrual cycle (taking the day of ovulation as day 0), using ultrasound estimates of mean follicular diameter, uterine volume, and endometrial thickness, and biochemical measurements of LH, FSH, oestradiol (E2), testosterone (T), progesterone (P) and sex-hormone-binding globulin (SHBG). Before clomiphene treatment, the anovulatory patients with PCO had significantly lower levels of SHBG and higher follicular phase concentrations of LH than all three control groups. After two cycles of clomiphene-induced ovulation, the serum LH concentration fell significantly and levels of SHBG increased significantly to levels similar to those found in spontaneously ovulating women with normal ovaries. It is likely that the loss of the usual considerable rise in E2 in both the follicular and luteal phases of ovulatory cycles is the main reason for the low SHBG found in the PCO syndrome. The loss of the normal P-induced gonadotrophin suppression may be a factor in allowing LH levels to rise.     

Exercise induces two types of human luteal dysfunction: confirmation by urinary free progesterone

We have previously reported that during 2 months of strenuous exercise, untrained young women with documented ovulatory menstrual cycles developed secondary oligoamenorrhea and luteal phase defects. In this study we tested the hypothesis that such abnormalities arise by altered neuroendocrine regulation of menstrual hormone secretion and that weight loss potentiates such effects. We supply a detailed analysis of the 20 cycles, of the total of 53, in which luteal phase abnormalities occurred. During the control month and 2 exercise months, all subjects collected daily overnight urine samples for the determination of LH, FSH, estriol (E3), and free progesterone (P) excretion by RIAs and creatinine by chemical assay. The characteristics of the abnormal luteal phase cycles were determined by comparing the excreted hormone levels and patterns during the control cycles with those of exercise cycles. The area under the curve (AUC) for each hormone was calculated for the follicular and luteal phases of each cycle. Six of the exercise cycles exhibited an inadequate luteal phase. This was characterized by a mean integrated P area of 202.4 (SEM, -61.8) nmol/day.nmol creatinine, compared with 331.7 (SEM, 64.7) during the corresponding control cycles, over a period of 9 or more days after the urinary LH peak to the onset of menses. Fourteen of the exercise cycles exhibited a short luteal phase. This was characterized by a mean integrated P area of 75.9 (30.9) nmol/day.nmol creatinine, compared to 267 (61.7) during the corresponding control cycles, over a span of 8 days or less from the urinary LH peak to the onset of menses. Additional abnormalities occurred only in the short luteal phase cycles. These included an increase in the length and AUC for E3 of the follicular phase and a decrease in the AUC of LH during the luteal phase. We conclude that the initiation of strenuous endurance training in previously ovulating untrained women frequently leads to corpus luteum dysfunction associated with insufficient P secretion and, in the case of short luteal phase cycles, decreased luteal phase length. That exercise may alter the neuroendocrine system is suggested by a delay in the ovulatory LH peak in spite of increased E3 excretion; moreover, less LH is excreted during the luteal phase. The lack of positive feedback to estrogens and decreased LH secretion during the luteal phase could compromise corpus luteum function. In contrast, decreased free P excretion was the sole abnormality noted in menstrual cycles with an inadequate luteal phase.     

Examination of the role of 'non-functional' corpora lutea in the female rat

In rats with 5 day reproductive cycles, 'anovulatory' cycles were induced by blockade of ovulation with sodium pentobarbitone injected at pro-oestrus. Such anovulatory cycles were characterized in the ovaries by gradual atresia of the large follicles present at the time of the injection and the growth of a new cohort destined for the next ovulation. In the vaginal smears, anovulatory cycles were indistinguishable from normal ovulatory cycles. The serum concentrations of progesterone remained at baseline levels during dioestrus of anovulatory cycles whereas increased concentrations of progesterone were observed during dioestrus of ovulatory cycles. It is concluded that the 'non-functional' corpora lutea of the cycle are the source of dioestrous progesterone. The length of anovulatory cycles after a single injection of pentobarbitone was 5 days despite the absence of any increase in progesterone concentrations during dioestrus. It is concluded that progesterone production during dioestrus plays no major role in the control of the duration of 5 day reproductive cycles.     

The matrix metalloproteinase system: changes,regulation, and impact throughout the ovarian and uterine reproductive cycle

The ovary and uterus undergo extensive tissue remodeling throughout each reproductive cycle. This remodeling of the extracellular environment is dependent upon the cyclic hormonal changes associated with each estrous or menstrual cycle. In the ovary, tissue remodeling is requisite for growth and expansion of the follicle, breakdown of the follicular wall during the ovulatory process, transformation of the postovulatory follicle into the corpus luteum, as well as the structural dissolution of the corpus luteum during luteal regression. In the uterus, there is extraordinary turnover of the endometrial connective tissue matrix during each menstrual cycle. This turnover encompasses the complete breakdown and loss of this layer, followed by its subsequent regrowth. With implantation, extensive remodeling of the uterus occurs to support placentation. These dynamic changes in the ovarian and uterine extracellular architecture are regulated, in part, by the matrix metalloproteinase (MMP) system. The MMP system acts to control connective tissue remodeling processes throughout the body and is comprised of both a proteolytic component, the MMPs, and a regulatory component, the associated tissue inhibitors of metalloproteinases. The current review will highlight the key features of the MMPs and tissue inhibitors of metalloproteinases, focus on the changes and regulation of the MMP system that take place throughout the estrous and menstrual cycles, and address the impact of the dynamic tissue remodeling processes on ovarian and uterine physiology.     

Family History of Alcoholism in Women with Generalized Anxiety Disorder Who Have Premenstrual Syndrome: Patient Reports of Premenstrual Alcohol Consumption and Symptoms of Anxiety

This study sought to determine whether family history of alcoholism is related to patient reports of premenstrual alcohol consumption and whether family history of alcoholism is related to severity of anxiety-related symptoms, in women who suffer simultaneously from both premenstrual syndrome and generalized anxiety disorder. Fifty-four women with generalized anxiety disorder and prospectively demonstrated premenstrual syndrome were questioned about family history of alcoholism and alcohol consumption patterns across the menstrual cycle. Seventy-six percent of the sample reported having an alcoholic first- or second-degree relative. Furthermore, 74% of those women having a paternal-side family history of alcoholism, but only 22% of those without such a family history, reported increased alcohol consumption premenstrually. Forty-one of these women were assessed by means of psychiatric rating scales during both the premenstrual and follicular phases of the menstrual cycle. During the premenstrual, but not the follicular, phase of the menstrual cycle, women with a paternal-side family history of alcoholism experienced more severe anxiety-related somatic, but not psychic, symptoms of anxiety, than those without such a family history. These findings suggest that family history of alcoholism may be related to premenstrual alcohol consumption patterns and to the severity of premenstrually experienced somatic symptoms of anxiety in women with premenstrual syndrome, and that these women may be self-medicating with alcohol.     

PROLONGED FOLLICULAR PHASE AND DEPRESSED GONADOTROPHINS FOLLOWING HYSTERECTOMY AND CORPUS LUTE-ECTOMY IN WOMEN WITH PREMENSTRUAL TENSION SYNDROME

In an attempt to obtain further information on the aetiology of premenstrual syndrome (PMS), the endocrine changes following enucleation of the corpus luteum in the mid-luteal phase of the cycle were studied in seven patients with PMS, and the results compared to details of seven control patients undergoing hysterectomy for menstrual problems. In the luteal phase, before surgery, the concentration of progesterone and FSH was lower, while that of oestradiol was slightly higher, in women with PMS. Following enucleation of the corpus luteum, follicular development and ovulation recommenced more slowly in women with PMS compared to controls (time to ovulation: 21 (range 18-24, vs 19(14-20) d, P less than 0.01). During the follicular phase there was no difference between the two groups in the concentration of oestradiol. The rise in concentration of FSH following enucleation was delayed in patients with PMS, and the serum FSH concentration was significantly lower during the late follicular phase of the cycle, but not during the mid follicular phase. The results suggest that these women with PMS have a more sensitive 'feed-back' than the controls, resulting in a lower preovulatory FSH level even though the oestradiol levels were not different. The results also suggest that the abnormalities described during the preoperative luteal phase are associated with the delay in the initial FSH rise.     

Endocrine response determines the clinical outcome of pulsatile gonadotropin-releasing hormone ovulation induction in different ovulatory disorders

To accrue systematic information in different ovulatory disorders on the precise relationship among endocrine response, clinical outcome, and the occurrence of complications, we treated 114 patients with pulsatile GnRH (2.5-5.0 micrograms, iv, every 60 min) for 187 cycles and compared them to 20 normal menstrual cycles. Thirty of these patients had primary hypogonadotropic amenorrhea (PHA; 40 cycles), 33 had other forms of hypogonadotropic hypogonadism (HH; 55 cycles), and 51 had polycystic ovary syndrome (PCOS; 92 cycles). Daily blood samples were drawn for hormone determinations. In PCOS, 50 cycles were preceded by GnRH analog suppression. PHA treatment cycles were characterized by the reestablishment of a normal endocrine pattern, almost no dose-related endocrine differences, elevated ovulatory (93%) and conception rates (23%), and no multiple pregnancies. In the HH subjects the ovulatory (91%) and pregnancy rates (31%) were high; however, while the lower GnRH dose elicited a normal endocrine pattern, the 5-micrograms dose induced excessive folliculogenesis and high estradiol levels and was associated with most of the multiple pregnancies of this study (three of four). GnRH analog suppression was successfully used to avoid recurrence of ovarian over-stimulation in two HH subjects. Finally, GnRH analog suppression in PCOS permitted normalization of the follicular phase endocrine pattern, achievement of good ovulatory (76%) and pregnancy (28%) rates, and avoidance of multiple pregnancies; however, luteal phase steroid secretion was abnormal, and the abortion rate remained elevated (43%). Obesity was associated with a reduced ovulatory rate in PCOS, but not in hypogonadotropic, subjects. Thus, we can conclude that in pulsatile GnRH ovulation induction: 1) a profound hypogonadotropic condition, whether spontaneous as in PHA or induced with GnRH analogs as in other ovulatory disorders, is associated with optimal menstrual cycle restoration, high ovulatory and conception rates, and virtually absent risks of multiple pregnancy; 2) residual hypothalamic activity in HH may be responsible for supraphysiological pituitary-ovarian stimulation and result in multiple pregnancy unless a low GnRH dose (2.5 micrograms/bolus) or GnRH analog pretreatment is employed; 3) obesity does not affect treatment outcome in hypogonadotropic patients; and 4) the high spontaneous abortion rate in PCOS may be related to corpus luteum dysfunction.     

Perimenstrual Symptoms in Women with Diabetes Mellitus and the Relationship to Diabetic Control

Four hundred and six insulin-dependent diabetic women completed a Menstrual Health Questionnaire published in Balance. Sixty-seven percent of women experienced changes in blood glucose levels or glycosuria premenstrually and 70% during the menstrual phase. Changes were more common in women who regarded themselves as suffering from premenstrual syndrome. Those experiencing premenstrual craving for sweet foods tended to have higher blood glucose levels or more glycosuria at those times. This may be a consequence of some women indulging their craving. Premenstrual symptoms were not caused by hypoglycaemia. When compared with age-matched non-diabetic women responding to a similar questionnaire, the diabetic women had a later menarche and, among those not on steroidal contraceptives, were more likely to report very irregular menstrual cycles. Among those regarding themselves as sufferers of premenstrual syndrome, diabetic women had less severe premenstrual symptoms than non-diabetic women. When women from these two self-designated diabetes mellitus syndrome suffering groups were matched for severity of premenstrual depression, differences still persisted in the severity of some symptoms perimenstrually, raising the possibility that in some way diabetes may alter women's experience of menstrual cycle-related symptoms.     

Reproductive endocrine effects of intranasal administration of progesterone to adult female rhesus monkeys

Adult female rhesus monkeys exhibiting normal ovulatory menstrual cycles were treated with progesterone nasal sprays. Animals in group A (n = 9) were treated with the solvent only (controls). Animals in groups B (n = 6), C (n = 17) and D (n = 7), respectively, were treated with a daily dose of 0.4, 2 and 10 micrograms of progesterone and the spraying was done between days 5-14 of the cycle. Ovulation was monitored by laparoscopy on day 20. The serum endocrine profile throughout the treated menstrual cycle was studied with respect to oestradiol and progesterone. Bioactive luteinizing hormone (bLH) was studied in blood samples taken on the day of the mid-cycle oestradiol peak, 2 days before, and 2 days after. The menstrual cycle was divided into two phases with respect to the mid-cycle oestradiol peak: phase I was taken to include day 1 of the cycle to the day of the oestradiol peak, and the remaining part of the menstrual cycle was considered to be phase II. The serum-endocrine profile in the controls was similar to that observed in normal ovulatory menstrual cycles. However, in the progesterone-treated groups three types of menstrual cycles were discernable on the basis of the serum endocrine profile. In the type I menstrual cycle, observed only in group C (n = 10), the mid-cycle bLH peak was abolished and the progesterone levels remained low throughout the cycle. Laparoscopy revealed these to be anovulatory cycles.(ABSTRACT TRUNCATED AT 250 WORDS)