Spontaneous Menstruation Research Articles

Prevalence and genesis of endometriosis

A group of 1542 pre-menopausal Caucasian women were assessed prospectively to investigate the prevalence of endometriosis. The women were either having laparoscopy because of infertility (n = 654), undergoing laparoscopic sterilization (n = 598), having laparoscopy because of chronic abdominal and pelvic pain (n = 156) or undergoing abdominal hysterectomy for dysfunctional uterine bleeding (n = 134). Endometriosis was noted more frequently among women being investigated for infertility (21%) than among those undergoing sterilization (6%). Among those being investigated for chronic abdominal pain, the incidence of endometriosis was 15%, while among those undergoing abdominal hysterectomy, it was 25%. In all groups the total duration of combined pill usage was significantly higher in patients who had a normal pelvis compared to those with endometriosis. It is suggested that among susceptible women, both fertile and infertile, a prolonged period of regular spontaneous menstruation may play a causative role in the genesis of endometriosis.

Acetyl‐1‐carnitine as possible drug in the treatment of hypothalamic amenorrhea

Several neuroendocrine disregulations have been demonstrated in patients with hypothalamic amenorrhea, but a definite therapeutic strategy has not yet been found. Since acetyl-l-carnitine (ALC) has been reported to have a specific effect on central cholinergic, serotoninergic, dopaminergic and opioidergic systems, 20 patients with hypothalamic amenorrhea were treated with ALC (2 g/day, per os). Both the clinical efficacy and the endocrine parameters were evaluated after 6 months. The patients were subdivided in two groups according to their LH plasma levels: A) hypogonadotropic: 10 subjects with plasma LH less than 3 mIU/ml, and B) normogonadotropic: 10 subjects with plasma LH greater than 3 mIU/ml. All subjects underwent: 1) a pulsatility study (4 h sampling every 10 min), 2) GnRH test (two bolus injections of 10 micrograms at time 0 and +120), 3) TRH test (200 micrograms). These parameters were evaluated before and after 6 months of ALC administration. The occurrence of a spontaneous menstruation was observed in 6 out of 10 hypogonadotropinemic and in 4 out of 10 normogonadotropinemic patients. Menstrual bleeding occurred between the 3rd and the 6th month of therapy. Major hormonal changes after ALC administration were observed in the hypogonadotropic subjects. They showed a significant increase in baseline plasma LH levels (from 0.9 +/- 0.1 to 3.5 +/- 0.7 mIU/ml, p less than 0.05) (mean +/- SEM), a significant increase in LH pulse amplitude (p less than 0.01) with no changes in LH pulse frequency, and a significantly increased response of LH to the latter GnRH bolus during the GnRH test. Hypogonadotropic patients also showed a significant increase in both estradiol (from 18.8 +/- 2.5 to 48 +/- 3.3 pg/ml, p less than 0.05) and PRL (from 6 +/- 1 to 11.4 +/- 1.7 ng/ml, p less than 0.05). No significant differences were observed in the hormonal parameters of normogonadotropic patients after 6 months of ALC therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Histological and clinical features of menstruation induced by the antiprogestin mifepristone (RU486) compared to menstruation occurring spontaneously.

The clinical and histological features of menstruation induced by a single oral dose of mifepristone were compared to those in normal spontaneous menstruation to aid understanding of the mechanism of endometrial shedding. 30 healthy volunteers, sterilized or seeking sterilization, were given a single oral dose, ranging from 5-200 mg mifepristone (RU-486) in the 1st half of the luteal phase, timed by the LH surge. Endometrial biopsies were taken on that day or the day after the 1st episode of bleeding for histological examination. Quantitative histological features on a 15 item scale were compared to those seen in women having spontaneous menses. 7 of 15 features differed between the 2 groups. Bleeding induced by mifepristone was associated with the following endometrial characteristics: increased gland cell height, reduced secretion in gland lumen, increased volume fraction of gland occupied by cells and nuclei, increased pseudostratification of gland cells, reduced stromal predecidual reaction, as judged by glycogen and fat content, and reduced leukocyte infiltration in the stroma. Thus there was less gland activity and an appearance of more cell packing, taller and more pseudostratified cells. The features in common with normal menses were mitotic activity in both glands and stroma, secretory vacuoles, edema and extravasation. Clinically the amount and duration of menstrual flow induced by mifepristone was similar to normal menses, suggestive of a similar hemostatic process.

Nonsurgical management of unruptured tubal pregnancy with intra-amniotic methotrexate: preliminary report of two cases

Two cases of unruptured tubal pregnancy were managed conservatively by the aspiration and injection of 50 mg methotrexate into the amniotic sac with the use of a vaginal ultrasound transducer under local anesthesia. Both women experienced no pain or side effects and went home within 12 hours. Spontaneous menstruation began in both cases within 6 weeks of the procedure.

Melatonin day-night rhythms in subjects with Turner Syndrome

The day-night rhythms of serum melatonin (MEL) were investigated in 10 subjects with Turner syndrome,aged 2-17 years.Five had karyotype 45 XO,4 had 45 XO/46 XX and one 45 XO/46XX/47XXX mosaicism.Serum MEL concentrations were determined according to the RIA procedure of Rollag and Niswander,using the antibody kindly donated by Dr. Niswander.Serum LH,FSH and PRL were measured by routine RIAs.MEL patterns were abnormal in all subjects. 1.Day-time values were higher than normal (135±88 vs. 55±26,p < 0.05), as already observed in a previous study (Gupta et al, 1983).2.Night peak MEL values were in the prepubertal range irrespective of the age and developmental stage of the subject. 3.Desynchronized ultradian rhythms were present in all subjects except one,a 17-yrs. old XO/XX girl who had spontaneous menstruations. 4.No relationship between MEL serum levels and gonadotrophin concentrations were found. 5.In some of the patients the night elevation in serum PRL levels was very pronounced. These data illustrate the principle that chromosomal abnormality may be antecedent to the development of aberrations in relation to the pineal biorhythm.However,this is simply a hypothesis which should be examined further.

Effects of Bromocriptine-induced Pregnancy on Prolactin-secreting Pituitary Tumours

Twenty-eight women with hyperprolactinaemia and amenorrhoea received bromocriptine treatment which resulted in 31 term pregnancies. Bromocriptine treatment was stopped as soon as pregnancy was established. Nineteen of the women had radiological signs of a pituitary tumour. The pregnancies were clinically uneventful in all cases except one who developed headache. Post-partum sellar X-ray showed pregnancy-induced enlargement of the pituitary fossa in 4 of the 28 women. Regression of the radiological changes occurred in 3 of the 4 women within 2 years after the delivery. The women with abnormal sellar X-rays had no difference in the mean prolactin levels before treatment and after pregnancy and lactation while all the women with normal sellae had lower prolactin levels after pregnancy than before. Three women resumed regular spontaneous menstruations after pregnancy and lactation but only one conceived again. Thus, serious pituitary tumour complications are rare in hyperprolactinaemic women with bromocriptine-induced pregnancies. The pregnancy does not worsen the condition. Resolution of hyperprolactinaemia after bromocriptine-induced pregnancy is an unfrequent finding.

Pregnancy and gonadal dysgenesis

SummaryThe loss or deletion of an X-chromosome usually causes rapid atresia of germ cells, so that at the time of birth, or soon afterwards, only non-functioning streak gonads remain. The process of atresia is sometimes incomplete and, in such cases, pubertal changes, spontaneous menstruation and occasional pregnancies have been reported (Kable and Yussman, 1981). The purpose of this paper is to report a pregnancy occurring in a patient with gonadal dysgenesis who was taking an oestrogen-progestagen oral contraceptive.

Interactions between psychosomatic conflicts and gonadotropin secretion.

This present paper represents an attempt to correlate hormonal patterns and psychoanalytical data in 30 patients with secondary amenorrhea. Based on psychoanalytical data and the maximal LH response to GnRH, which were obtained independently, the patients were divided into two groups presenting differing psychosomatic symptomatologies. Patients with severe psychosomatic disease (group A) complaining predominantly of somatic discomfort, exhibited a weak pituitary response to GnRH. Patients presenting mainly mental symptoms were found to be less affected by the psychosomatic disease (group B). The LH responses to GnRH were only moderately impaired in these patients. Seven patients of group A underwent psychotherapy, resulting in a resumption of regular menses in 4 patients. Eight untreated controls of this group who remained amenorrheic exhibited unaltered gonadotropin in levels. All patients of group B being treated by psychotherapy resumed regular menses, while 5 of 7 control patients developed spontaneous menstruation. The progress of sexual maturation in these patients is correlated with increasing pituitary LH response to GnRH. The present study provides evidence that the degree of a psychosomatic disturbance resulting in secondary amenorrhea is reflected by the pattern of plasma LH after GnRH stimulation.

Effects of bromocriptine-induced pregnancy on prolactin-secreting pituitary tumours.

Twenty-eight women with hyperprolactinaemia and amenorrhoea received bromocriptine treatment which resulted in 31 term pregnancies. Bromocriptine treatment was stopped as soon as pregnancy was established. Nineteen of the women had radiological signs of a pituitary tumour. The pregnancies were clinically uneventful in all cases except one who developed headache. Post-partum sellar X-ray showed pregnancy-induced enlargement of the pituitary fossa in 4 of the 28 women. Regression of the radiological changes occurred in 3 of the 4 women within 2 years after the delivery. The women with abnormal sellar X-rays had no difference in the mean prolactin levels before treatment and after pregnancy and lactation while all the women with normal sellae had lower prolactin levels after pregnancy than before. Three women resumed regular spontaneous menstruations after pregnancy and lactation but only one conceived again. Thus, serious pituitary tumour complications are rare in hyperprolactinaemic women with bromocriptine-induced pregnancies. The pregnancy does not worsen the condition. Resolution of hyperprolactinaemia after bromocriptine-induced pregnancy is an unfrequent finding.

Menarchal age in Nigerian schoolgirls: its relationship to their height, weight and menstrual profile.

Interviews with 119 students in a girls' residential secondary school in Ondo, Nigeria, revealed that 105 of them had menstruated, their mean age at menarche being 13.85 years, their mean height 156.8 cm and their mean weight 51.13 kg. The duration of menstrual bleeding was 4.43 days, the heaviest occurring at 1.82 days. Dysmenorrhea was reported by 32%. There was no correlation between the weight/height ratio and the mean age of the study group who were menstruating and the 14 students who were not. However, the difference in mean weight and height of those who had and had not attained menarche was significant. It is suggested that certain levels of weight and height are critical to achievement of spontaneous menstruation.

Pregnancy-Specific β1-Glycoprotein and Chorionic Gonadotropin-Like Immunoreactivity during the Latter Half of the Cycle in Women Using Intrauterine Contraception*

In a cross-sectional study, the serum levels of pregnancy-specific beta 1-glycoprotein (PSBG), hCG, human LH, and progesterone were measured by RIAs during 94 mid or late luteal phases of 69 women using oral contraceptives. Subsequent spontaneous menstruation took place in every cycle. None of the women using oral contraceptives had any PSBG or hCG-like immunoreactivity in serum. In women with intrauterine devices, PSBG was found in six cycles (6.4%) and hCG-like immunoreactivity was demonstrated in one cycle only, where PSBG also was present. In two out of six PSBG-positive cycles, menstruation was delayed by 5 and 16 days. Although rare, the transient occurrence of trophoblastic antigens in women using intrauterine contraception is taken as evidence for an occult pregnancy in these apparently infertile cycles.

Primary amenorrhoea: the ambiguous non-entity.

Hypothalamic-pituitary activity was investigated in 20 women with primary amenorrhoea, in whom gonadal dysgenesis and lower Müllerian duct anomalies had been excluded. There was no specific or uniform pattern of response to luteinising hormone-releasing hormone and no evidence of a common defect at pituitary-hypothalamic level to account for the absence of spontaneous menstruation. Six women had hyperprolactinaemia; of these five had radiological evidence of pituitary enlargement. The conventional distinction between "primary" and "secondary" amenorrhoea should be abandoned, and, in common with current practice for other endocrine glands, primary amenorrhoea should indicate an abnormality of the gonad itself and secondary amenorrhoea an abnormality that results from hypothalamic-pituitary dysfunction.

Arrhenoblastoma of the ovary with virilism: A case report with hormonal study

An intermediate type arrhenoblastoma of the left ovary in a 25-yr-old infertile woman is reported, in association with a teratoma. Basal plasma testosterone was markedly elevated. It rose under attempts at dexamethasone inhibition, and declined under norethindrone therapy. Following surgery the patient improved in her virilizing syndrome, resumed spontaneous menstruation and became pregnant. The histologic and hormonal characteristics of this case and correlated and discussed leading to the assumption that the ovarion stromal reaction rather than the tumor itself is the source of testosterone.

Work in progress menstrual induction with PGF2α and PGE 2

The "prostaglandin impact" (PGI), a massive intrauterine dose of PG, converts the refractory pregnant uterus into a reactive organ by provoking a regulatory imbalance. This regulatory conversion releases the endogenous mechanism of menstruation or abortion. During initial studies, PGI successfully provoked menstrual induction (MI) in 22 and subsequently in 65 volunteers. These results were confirmed and complemented by 2 independent trials in 14 and 36 gravidas respectively. The best clinical outcome was obtained in 20 volunteers, when a "PG-Pellet" (a mini-suppositorium) was inserted in utero, containing only 2.5 mg PGF2alpha. These 157 trials in sedated volunteers had the common features of over 90% efficiency, transient and medically acceptable side effects and infrequent complications. The present study of 542 volunteers focused upon the collection of clinical data regarding efficacy, side effects and complications of MI. All patients had committee approval for legal abortion, during the 2nd week of their missed menstrual period. They volunteered to participate because of their preference for pharmacological rather than surgical pregnancy termination. The clinical outcome of the 542 MI with 5 mg PGF2alpha (428 cases) and 1.5 mg PGE2 (114 cases) was identical. On the average, 95% of the gravidas had complete evacuation of the uterus with the clinical symptoms of delayed menstruation rather than abortion; they experienced spontaneous menstruation in 34 days after having received a single dose of PG.

The investigation of ovarian function by measurement of urinary oestrogen and pregnanediol excretion.

Urinary oestrogen and pregnanediol excretion was measued daily ("daily monitoring") for a complete cycle in 20 normally menstruating women, in one patient with an anovulatory cycle and for 28 days in a patient with secondary amenorrhoea. The measurements were also performed on urine specimens collected at weekly intervals for 4 to 6 weeks ("weekly tracking") from 506 patients with evidence of abnormal ovarian function. These included 9 patients with primary amenorrhoea, 132 patients with secondary amenorrheoa, 138 patients with oligomenorrhoea and 227 patients with evidence of ovarian dysfunction and cycle lengths of 25 to 42 days. The results were subjected to statistical analysis. In the normal cycles, ovulation could be identified on the criteria of a rising pregnanediol value reaching or exceeding 2-0 mg. per 24 hours for a period of 7 days or more. Valid conclusions on the overall mean oestrogen and pregnanediol values for a complete cycle could be made from the results of weekly tracking, irrespective of which day the tracking commenced. Correlations were obtained by comparing the mean and maximum urinary oestrogen values and the variability of the values with the evidence of ovarian function indicated by the clinical classifications of the patients, the duration of the disorders and the subsequent occurrence of uterine bleeding. Mean oestrogen values of 10 mug. per 24 hours or less were associated with lack of ovarian function. For values higher than this a discriminant function based on both the mean oestrogen value and the variability of the oestrogen values was useful in predicting onset of spontaneous menstruation. A single urine specimen collected 4 to 8 days before onset of menstruation showing a raised pregnanediol value of 2-0 mg. per 24 hours or more provided a valid test for ovulation in women with regular cycles, and a single urine specimen giving an oestrogen value of 10 mug per 24 hours or less gave a valid indication of absent ovarian function in women with amenorrhoea for two years or more. In all other circumstances serial sampling at weekly intervals provided a valid assessment of ovarian activity. Application of these principles allows the greatest amount of information on ovarian function to be obtained with the greatest economy of effort.

Intrauterine injection of prostaglandin F 2α for termination of early pregnancy in out-patient

Prostaglandin F 2α administered as single intrauterine injection was used for termination of very early pregnancy in 34 out-patients. Twelve patients were induced with 1.0 mg, 18 patients with 2.0 mg and 4 patients with 4.0 mg of PGF 2α. After 2 weeks, abortion was complete in 58% induced with 1.0 mg, in 78% induced with 2.0 mg, and in all 4 patients induced with 4.0 mg. After 3 weeks, abortion was complete in 83% induced with 1.0 mg and in 100% induced with 2.0 mg. There was one failure, which occurred in the group treated by using 1.0 mg PGF 2α. Immediate side-effects were kept at an acceptable level with a very mild premedication. No serious complications occurred but curettage was performed on 2 patients because of bleeding. Spontaneous menstruation started in the 1.0 mg group within an average of 33 days (range 23–60), in the 2.0 mg group within an average of 36 days (range 25–61). The use of 2.0 mg PGF 2α for the routine termination of very early pregnancy is recommended.

INTRAUTERINEINJECTION OF PROSTAGLANDIN F2α FOR TERMINATION OF EARLY PREGNANCY IN OUT‐PATIENT

Abstract. Prostaglandin F2α administered as single intrauterine injection was used for termination of very early pregnancy in 34 outpatients. Twelve patients were induced with 1.0 mg, 18 patients with 2.0 mg and 4 patients with 4.0 mg of PGF2α. After 2 weeks, abortion was complete in 58 % induced with 1.0 mg, in 78 % induced with 2.0 mg, and in all 4 patients induced with 4.0 mg. After 3 weeks, abortion was complete in 83 % induced with 1.0 mg and in 100% induced with 2.0 mg. There was one failure, which occurred in the group treated by using 1.0 mg PGF2α. Immediate sideeffects were kept at an acceptable level with a very mild premedication. No serious complications occurred but curettage was performed on 2 patients because of bleeding. Spontaneous menstruation started in the 1.0 mg group within an average of 33 days (range 23‐60), in the 2.0 mg group within an average of 36 days (range 25‐61). The use of 2.0 mg PGF2α for the routine termination of very early pregnancy is recommended.

Psychological factors, psychiatric illness and amenorrhoea after oral contraceptive treatment.

The occurrence and causative role of psychological factors reported as hypothalamic amenorrhea that may be present in amenorrhea after discontinuing oral contraceptive (OC) medication was studied. Patients were 75 17-30 year old women with at least 6 months amenorrhea immediately following discontinuance of OC therapy. All of the women volunteered for a standardized psychiatric interview preceded by psychological testing using Form B of the Eysenck Personality Inventory and the Marke-Nyman Temperament Scale. Regular menstrual periods before OC treatment were reported by 46 women. The other 29 had irregular cycles usually with oligomenorrhea with intervals of 4-12 weeks. Of the 46 women with regular cycles 13 reported sporadic cycles of secondary amenorrhea lasting 2-6 months. Of the 29 reporting irregular cycles 9 had similar short periods of amenorrhea. Dysmenorrhea was reported by 38 women. Most of these had been relieved by OC therapy. A ll but 5 were nullipara. Duration of OC treatment had been 2-64 months. Combined type preparations were mostly used. 10 women with syndromes of emotional instability during OC treatment were relieved of symptoms after discontinuance of the treatment. Duration of the amenorrhea in patients studied had ranged from 6 to 49 months. Only 15 women resumed spontaneous menstruation within 12 months after discontinuing OC treatment. The duration of amenorrhea and the length of the treatment period seemed unrelated. Phobias or compulsive behavio r were found in 9 only 1 of them being incapacitated. Periods of insomia had occurred in 31. Women who had experienced stressful life events had higher neuroticism scores and lower solidity scores (p less than .05). The possible importance of other factors is noted as many of the women had not developed amenorrhea on previous occasions when they had discontinued OCs. Women with a previous disturbance of the hypothalamic-pituitary-ovarian axis such as oligomenorrhea were found in greater proportion than expected. All cases in the series of 75 were diagnosed as hypothalamic. It is suggested that emotional factors may play a considerable role in the genesis of amenorrhea after the use of an OC agent. The value of a psychiatric interview is stressed in estimating etiological factors in secondary amenorrhea irrespective of its relation to discontinuance of OC therapy.

Amenorrhoea in anorexia nervosa: assessment and treatment with clomiphene citrate.

Seven patients with anorexia nervosa were studied, three during the acute stages of the illness, and four in whom weight gain had been achieved, but who suffered from persistent amenorrhoea of 18 to 79 months' duration.In the acute stage all patients had low serum luteinizing hormone (LH) levels which were unresponsive to clomiphene citrate. In those who had regained weight the mean basal LH levels were normal, and they responded to clomiphene with an initial doubling of serum LH during administration of the drug, followed by a second peak of serum LH four to seven days after the drug was stopped. Menstruation occurred in these patients 13 to 19 days after the clomiphene was discontinued, and in two patients regular spontaneous menstruation was initiated.The low LH levels unresponsive to clomiphene in the acute stage provide evidence for a hypothalamic abnormality in anorexia nervosa. After regain of body weight the drug seems to be effective in treating the amenorrhoea which may be persistent.

Effect of Daily Administration of 0.5 Mg. of Chlormadinone Acetate on Plasma Levels of Follicle-Stimulating Hormone, Luteinizing Hormone, and Progesterone During the Menstrual Cycle

Investigators at Cornell University Medical College and New York Medical College in New York City studied the effects of chlormadinone acetate administration on hormone levels in an effort to better understand the contraceptive mode of action of this drug. 9 healthy women had 2 consecutive cycles studied. While the first cycle was a control cycle the second one involved chlormadinone acetate administration .5 mg/day from Day 1 to Day 28 or until the occurrence of spontaneous menstruation if this delayed until after Day 28. Basal body temperature was recorded each morning. Chlormadinone tended to suppress the mean luteinizing hormone and follicle stimulating hormone peaks and the plasma progesterone levels. 3 patients are believed to have ovulated during the experimental cycle but probably in 2 of them the luteal phase was less pronounced than a normal luteal phase. However 1 of the remaining 6 patients had failed to ovulate in the control cycle. Though limitations exist in the study of the parameters investigated here such study is necessary since direct evidence of ovulation (e.g. pregnancy observation of corpus luteum) is usually unobtainable.