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Uterine leukocytes and decidualization.

The transformation of endometrium into decidua is an essential feature of normal implantation and pregnancy. There is a close association with an unusual leukocyte population, uterine natural killer (NK) cells, and onset of decidualization. These uterine NK cells are seen in close contact with stromal cells ultrastructurally and are also seen encircling vessels and glands. The possibility that uterine NK cells in the late secretory phase and in early decidua may be important in initiating and maintaining decidualization is raised. In contrast, the death of uterine NK cells could be an early event in the onset of endometrial breakdown at menstruation. The period between implantation and menstruation (7-14 days after luteinizing hormone surge) is the time when implantation is known to be particularly vulnerable. In this review, the possibility that uterine leukocytes might influence the critical decision that the mid- to late secretory endometrium must make either to decidualize or to undergo menstruation is explored.

Animals↗

Changes in expression of vascular endothelial growth factor and angiopoietin-1 and -2 in the macaque corpus luteum during the menstrual cycle.

To determine the temporal expression of vascular growth factors during the lifespan of the primate corpus luteum, experiments were designed to detect mRNA for vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1 and Ang-2 and to localize protein expression for VEGF in macaque luteal tissue during the menstrual cycle. Corpora lutea (n = 3-5/stage) were collected during the early (3-5 days post-luteinizing hormone surge), mid- (6-8 days), mid-late (10-12 days), and late (14-16 days) luteal phase and at menstruation (17-18 days). Reverse transcription-polymerase chain reaction products equated to cDNA for VEGF, Ang-1 and Ang-2 in all corpora lutea. VEGF mRNA levels increased (P: < 0.05) from early to mid-luteal phase and declined in the late luteal phase and at menstruation. Immunostaining for VEGF was detected in the cytoplasm of steroidogenic luteal cells, with the most intense staining in the early luteal phase. Ang-1 and Ang-2 mRNA expression was low in the early to mid-luteal phase but increased (P: < 0.05) at late luteal phase before declining at menstruation. These data suggest transcriptional control of VEGF, Ang-1 and Ang-2, as well as post-transcriptional control of VEGF, in macaque corpus luteum. Dynamic expression of angiogenic/angiostatic factors appears critical for development, maintenance and regression of the luteal microvasculature during the menstrual cycle.

Angiopoietin-1↗

Induction of endometriosis in the marmoset monkey (Callithrix jacchus).

Endometriosis is an estrogen-dependent gynaecological disease associated with pain and infertility, which occurs in humans and menstruating primates. In this study, the marmoset monkey (Callithrix jacchus), which is a non-menstruating primate with high circulating estrogen levels, was used to test firstly the hypothesis that endometriosis is based on uterine shedding into the peritoneal cavity, secondly to study the pathogenesis of endometriosis due to its estrogenic situation. Female marmoset monkeys (n = 29) were exposed to two different experimental procedures (non-invasive versus invasive) for intrapelvic placement of endometrial cells by uterine flushing over an experimental period of 2-3 years. First endometriotic foci were detected by colour Doppler ultrasound at the bladder, the uterus and the ovaries at the earliest after 4 months of either treatments. However, invasive induction was more effective in terms of the time-course of induction and the number of resulting endometriotic foci. The analysis of the endometriotic foci by histology, immunohistochemistry and molecular techniques allowed a division into two distinct groups: an initial developing stage occurred, which under further treatment led to the second stage of established endometriosis. Both procedures showed a treatment-dependent increase of vascular supply to the endometriotic foci over the experimental period. The invasive method induced the final established stage of endometriosis more rapidly, with the expression of steroid receptors, aromatase, 17betaHSD1 and CD10. Altogether, 72% of the treated marmoset monkeys developed endometriosis under our endometrial reflux protocols. Our data support the theory that endometriosis can be induced artificially in a non-menstruating primate (C. jacchus) by endometrial shedding into the peritoneal cavity. Because the marmoset is a primate with very high peripheral estrogen levels, this offers an interesting model for studying the pathogenesis of this estrogen-dependent disease, as well as for therapeutic impacts on enzymes involved in steroid metabolism.

17-Hydroxysteroid Dehydrogenases↗

The menstrual cycle and platelet 5-HT uptake.

The association between the onset of depressive illness and the paramenstruum has been reported. In the present study, we looked at changes in platelet 5-HT uptake in six healthy, regularly menstruating subjects on days 1, 10, and 24 of three consecutive menstrual cycles to explore possible biochemical bases for mood changes associated with menstruation. Platelet 5-hydroxytryptamine (5-HT) uptake was determined by suspension of platelet pellets in 0.5-5 microM hydroxy [G-3H] tryptamine [( 3H]-5-HT) creatinine sulfate solution at 37 degrees C and measurement of radioactivity of [3H]-5-HT in the platelets using liquid scintillation counting. Mood changes were measured using the Moos Menstruation Distress Questionnaire and the Spielberger State Anxiety Scale. Analysis of variance and trend analysis revealed significant elevation of Km and Vmax on day 24 of the cycle, which was consistent across the three menstrual cycles studied. A significant linear rise of "negative affect" across each cycle peaking on day 1 was detected. "Water retention" and "behavioral change" also peaked on day 1. No significant correlation, however, was obtained between the mood scores and platelet 5-HT uptake. These findings are discussed.

Adult↗

Severe acute asthma and the menstrual cycle.

Three cases of severe acute asthma associated with menstruation are reported. All required admission to an intensive therapy unit and intermittent positive pressure ventilation of the lungs for one week or more. Several bronchodilator drugs and anaesthetic agents were employed in an effort to reduce the severe bronchospasm. In each case, improvement appeared to coincide with the end of menstruation. An awareness of the association of asthma and menstruation by those involved in intensive therapy may help in the management of similar cases.

Acute Disease↗

Pituitary-ovarian function before, during and after the menopause: a longitudinal study.

The excretion of FSH, LH, oestrogens and pregnanediol was monitored once weekly in urine samples collected from eight peri-menopausal women aged 44-55 years (median, 52 years). Observations were commenced between 5 and 15 weeks before the menopause and were continued for 22-30 weeks after final menstruation. Amenorrhoea of greater than 2 years duration in association with a persistent elevation in gonadotrophin output was considered proof of the post-menopausal state. No clear hormonal change occurred at the time of the menopause. During the peri-menopause there is a transition from the regular ovulatory cycles of pre-menopausal women to the unvarying high gonadotrophin and low oestrogen excretion which is generally regarded as being characteristic of post-menopausal women. In the group studied, post-menopausal levels of FSH and LH were common before and episodes of high oestrogen excretion were not uncommon after final menstruation. Menstrual failure appeared to occur spontaneously at some stage during the transition from the pre- to the post-menopausal state, and not to be associated with its conclusion. From the hormonal point of view the immediately post-menopausal period could not be distinguished from the long cycles of peri-menopausal women. This suggests that an endometrial rather than a hormonal event might determine the time at which menstruation stops during the menopausal transition.

Adult↗

Clinical and endocrine studies on patients with amenorrhoea associated with weight loss.

Two hundred and forty-three patients with amenorrhoea associated with weight loss were studied. At the onset of amenorrhoea, regardless of percentage weight loss, basal levels of LH were low and LH responses to LHRH were impaired. However, both basal and stimulated levels of FSH were comparable to normal. With resumption of menstruation, the basal and stimulated levels of LH were found to rise to normal, while FSH responses continued to exceed normal. However, 16.6% of 66 unimproved cases had normal responses but remained amenorrhoeic. Furthermore, amenorrhoea persisted in 71% of 31 patients with complete recovery of body weight. No significant correlation was noted between percentage weight loss and responsiveness to LHRH, nor between recovery of body weight and resumption of menstruation. Return to normal weight is desirable for resumption of normal cyclic menstruation and hypothalamic-pituitary function, but is not always effective.

Adolescent↗

A study on the feasibility of suppressing ovarian activity following the end of postpartum amenorrhoea by increasing the frequency of suckling.

The aim of the study was to test the effect of increasing the frequency of breastfeeding upon ovarian function following the end of postpartum amenorrhoea. Women exclusively breastfeeding (n = 14) who experienced their first postpartum menstruation between the third and fifth month after delivery were randomly allocated to an experimental (n = 7) and a control (n = 7) group and studied during the next two cycles. Women in the experimental group agreed to increase the number of breastfeeding episodes per day throughout the second cycle. Blood samples were drawn twice a week from the first to the third postpartum menstruation for prolactin, oestradiol and progesterone determinations. The number of breastfeeding episodes per day and night and the length of each episode were recorded daily. An average frequency of 11 nursing episodes per 24 h was reported during the first study cycle in both groups. The experimental group increased by 50% the breastfeeding frequency after the second menstruation while the control group kept its spontaneous feeding pattern. The increase of suckling frequency occurred mainly during day hours. The total breastfeeding time per 24 h was not increased. The length of the menstrual cycle was not altered by the increased suckling frequency. The endocrine pattern differed neither between the first and second cycle of the experimental group nor between the experimental and control group, with the exception of PRL levels which were higher in the experimental group throughout both cycles. Twenty cycles (71%) showed progesterone values compatible with ovulation (greater than 9.5 nmol/l). The highest progesterone values and the highest oestradiol values observed in the ovulatory cycles of lactating women were within the range found in non-nursing fertile women. Plasma levels of PRL were significantly elevated in all cycles but one, in comparison with PRL levels in non-nursing women. It is concluded that if cyclic ovarian function is reestablished early in fully nursing women, a mere increase in the number of breastfeeding episodes, without augmenting total suckling time and the frequency of nocturnal episodes, does not provide a sufficient stimulus to resuppress the pituitary-ovarian axis.

Adult↗

Therapeutic amenorrhoea induced by endometrial irradiation technique in mentally retarded women: neuropsychiatric aspects.

Menstruation may cause many difficulties in the care of mentally retarded women. We have applied the low-dose endometrial after-loading irradiation method for the termination of menstruation of such persons. So far, we have studied 29 women during the period 1970-1978. Twenty-two of them had earlier received gestagen treatment for the same purpose. The radiation dose was chosen in such a way that the dose in the endometrium was 14 Gy, giving an ovarian dose of about 4 Gy. One treatment gave a cessation of menstruation in 22 patients and two had minor flow with no clinical inconvenience, but five required a repeated irradiation. The hormonal changes after radiotherapy were found to be minor. The need for tranquilizers did not change. There were some changes in the frequency of epileptic seizures, possibly due to the termination of gestagen treatment, which has antiepileptic effects. The care of four of the 21 in-patients became so much easier after radiotherapy that they could be transferred to home care.

Adolescent↗

Menarche and menstrual function in patients with myelomeningocele.

The aim of this study was to assess menarchal age, to clarify the role of heredity in the timing of menarche, and to examine the management of menses in girls and young women with myelomeningocele. All female patients aged three years or older attending a tertiary-care hospital clinic were eligible. A questionnaire was administered to each menstruating patient and, when possible, a menstruating sibling control. Most biological descriptors of menses were comparable for patients and sibling controls, but management of menses, routine gynecological care and attitudes about family planning differed. Girls with myelomeningocele menstruated significantly earlier than the US mean (10.25 years); as did the girls' mothers (11.91 years), but not their sisters. This finding may have biological significance, and a larger sample size is needed to confirm or refute it.

Adolescent↗

'Bad hair days', scalp sebum excretion and the menstrual cycle.

BACKGROUND: Many women complain that their hair is periodically unmanageable, popularly known as 'bad hair days' (BHDs). At an anecdotal level BHDs are more common around the time of menstruation and, in view of previous studies reporting menstrual variation in sebum excretion, the authors hypothesised that changes in scalp sebum levels during the menstrual cycle might contribute to perceive differences in hair quality. AIMS: To test whether there is a relationship between BHDs, the menstrual cycle and scalp sebum excretion. METHODS: Thirteen women were studied through three menstrual cycles. Sebum levels on the scalp and forehead were measured twice weekly using a Sebumeter and each subject kept a record of hair quality and hair washing practice. RESULTS: BHDs occurred throughout the menstrual cycle but were more common during menstruation. There was no discernible variation in sebum levels on the scalp or forehead during the menstrual cycle and there was no correlation between individual mean skin sebum levels and the frequency of BHDs. However, BHDs were more common in those women who washed their hair infrequently, although the association between the frequency of hair washing and BHDs just failed to reach statistical significance (p = 0.06). CONCLUSIONS: BHDs are more common during menstruation and in women who wash their hair infrequently. This may relate to a build-up of sebum on the hair but menstrual variations in the frequency of BHDs are unrelated to sebum levels.

Journal Article↗

How common is catamenial epilepsy?

Forty women of childbearing age with refractory epilepsy were asked to record their seizures, the first and last days of their menstrual periods, and symptoms of premenstrual tension for 3 consecutive months. By defining catamenial epilepsy as the occurrence of at least 75% of seizures each month in the 10-day time frame, which included the 4 days preceding menstruation and the 6 days after its onset, only 5 women (12.5%) were identified who fulfilled the criterion. Nevertheless, after the study was completed, 31 (78%) of these patients claimed that most of their seizures occurred near the time of and were exacerbated by menstruation. The patients with catamenial epilepsy reported no more symptoms of premenstrual tension than did the rest of the group. Clustering outside the menstrual cycle was noted in 4 other patients. Catamenial epilepsy is an uncommon condition. Patient claims about frequency of seizures in relation to menstruation are not always accurate. A standard definition should be adopted because the diagnosis has implications for management.

Adult↗

High nocturnal body temperatures and disturbed sleep in women with primary dysmenorrhea.

Primary dysmenorrhea is characterized by painful uterine cramps, near and during menstruation, that have an impact on personal life and productivity. The effect on sleep of this recurring pain has not been established. We compared sleep, nocturnal body temperatures, and hormone profiles during the menstrual cycle of 10 young women who suffered from primary dysmenorrhea, without any menstrual-associated mood disturbances, and 8 women who had normal menstrual cycles. Dysmenorrheic pain significantly decreased subjective sleep quality, sleep efficiency, and rapid eye movement (REM) sleep but not slow wave sleep (SWS), compared with pain-free phases of the menstrual cycle and compared with the controls. Even before menstruation, in the absence of pain, the women with dysmenorrhea had different sleep patterns, nocturnal body temperatures, and hormone levels compared with the controls. In the mid-follicular, mid-luteal, and menstrual phases, the dysmenorrheics had elevated morning estrogen concentrations, higher mean in-bed temperatures, and less REM sleep compared with the controls, as well as higher luteal phase prolactin levels. Both groups of women had less REM sleep when their body temperatures were high during the luteal and menstrual phases, implying that REM sleep is sensitive to elevated body temperatures. We have shown that dysmenorrhea is not only a disorder of menstruation but is manifest throughout the menstrual cycle. Furthermore, dysmenorrheic pain disturbs sleep, which may exacerbate the effect of the pain on daytime functioning.

Adult↗

Effects of menstrual cycle and oral contraceptive use on calf venous compliance.

Numerous studies have shown that the female sex hormones estrogen and progesterone have multiple effects on the vasculature. Thus our goal was to investigate the effects of estrogen and progesterone on calf venous compliance by looking for cyclic changes during the early follicular, ovulatory, and midluteal phases of the menstrual cycle and during high and low hormone phases of oral contraceptive use. Additionally, we wanted to compare the venous compliance of normally menstruating women, oral contraceptive users, and men. We studied eight normally menstruating women (23 +/- 1 yr of age) during the early follicular, ovulatory, and midluteal phases of the menstrual cycle. Nine triphasic oral contraceptive users (21 +/- 1 yr of age) were studied during weeks of high and low hormone concentrations. Eight men (23 +/- 1 yr of age) were studied twice within 2-4 wk. With the use of venous occlusion plethysmography with mercury in-Silastic strain gauges, lower limb venous compliance was measured by inflating a venous collection cuff that was placed on the thigh to 60 mmHg for 8 min and then reducing the pressure to 0 mmHg at a rate of 1 mmHg/s. Venous compliance was calculated as the derivative of the pressure-volume curves. There were no differences between early follicular, ovulatory, and midluteal phases of the menstrual cycle or between high and low hormone phases of oral contraceptive use (P > 0.05). Male venous compliance was significantly greater than in normally menstruating women (P < 0.001) and oral contraceptive users (P < 0.002). These data support a sex difference but also suggest that venous compliance does not change with menstrual cycle phase or during the course of oral contraceptive use.

Adult↗

Nasal mucosal swelling and reactivity during a menstrual cycle.

INTRODUCTION: Nasal stuffiness is a great problem for many women in the later part of pregnancy. OBJECTIVE: This study was performed to evaluate whether oestrogen causes nasal congestion and/or a hyperreactive reaction of the nasal mucosa. MATERIAL AND METHODS: Ten healthy fertile women were examined during menstruation. Nasal mucosal congestion was studied with rhinostereometry and acoustic rhinometry. The nasal mucosa was challenged with 3 doses of histamine solution to study nasal reactivity. Measurements were made 3 times during menstruation. To find the exact time of ovulation, when oestrogen reaches its peak value, intravaginal ultrasound tests were done and blood samples taken, to determine the oestrogen and progesterone levels. RESULTS: The nasal mucosa became hyperreactive to histamine in connection with ovulation, when the blood level of oestrogen reached its peak. This does not occur during the menstrual or the luteal phase. No significant alteration was found in the baseline position during the menstruation. CONCLUSION: There is a connection between high oestrogen level and nasal mucosal reactivity.

Adult↗

Evaluation of serum zinc-binding capacity during childbirth, in newborn infants and during the menstrual cycle.

This is a study of the value of total serum zinc, serum zinc per g of protein, serum zinc-binding capacity and serum zinc-binding capacity per g of protein in 102 pregnant women during childbirth and in the cord blood of their newborn infants. A control group is established by analyzing these parameters in 10 healthy non-pregnant women on the first day of menstruation and on the day of ovulation during two consecutive menstrual cycles. The total serum zinc and serum zinc per g of protein values found were significantly higher in cord blood than in maternal blood, and the binding capacity of zinc and of zinc per g protein were significantly higher in maternal blood. There is a negative correlation between total zinc and binding capacity and total zinc and binding capacity per g protein both in maternal and in cord blood. In the control group, the values of total zinc and zinc per g protein vary from one menstrual cycle to the next and between the different phases of each cycle. Zinc-binding capacity per g protein during ovulation is significantly lower than during menstruation. These results allow us to conclude that the rise of zinc-binding capacity and zinc-binding capacity per g protein in maternal blood during childbirth, and during menstruation in the control group, can be due to the effect of progesterone. The fact that zinc-binding capacity and zinc-binding capacity per g of protein are higher in maternal blood than in cord blood would confirm the existence of mechanisms which tend to increase binding of zinc in the fetus.

Adult↗

Long-term use of contraceptive depot medroxyprogesterone acetate in young women impairs arterial endothelial function assessed by cardiovascular magnetic resonance.

BACKGROUND: Depot medroxyprogesterone acetate (DMPA) inhibits proliferation of ovarian follicles, resulting in anovulation and a decrease in circulating estrogen; the latter action is potentially disadvantageous to cardiovascular health. We therefore investigated the vascular effects of long-term contraceptive DMPA in young women. METHODS AND RESULTS: Endothelium-dependent (hyperemia-induced flow-mediated dilatation [FMD]) and -independent (glyceryl trinitrate [GTN]) changes in brachial artery area were measured using cardiovascular magnetic resonance in 13 amenorrheic DMPA users (>1 year use; mean age 29+/-4 years) and in 10 controls (mean age 30+/-4 years, P=0.25) with regular menstrual cycles after validation of the technique. FMD and GTN responses were measured just before repeat MPA injection and 48 hours later (n=12) in DMPA users and during menstruation and midcycle (n=9) in controls. Serum-estradiol levels (S-estradiol) were measured at both visits. FMD was reduced in DMPA users compared with controls during menstruation (1.1% versus 8.0%, respectively P<0.01) without differences in GTN responses. S-estradiol levels in DMPA users were significantly lower than in controls during menstruation (58 versus 96 pmol/L, P<0.01). High levels of circulating MPA 48 hours after injection were not linked to an additional impairment in FMD (2.0% versus 3.1%, P=0.23). Estradiol levels were significantly correlated to FMD (r=0.43, P<0.01). CONCLUSIONS: Endothelium-dependent arterial function measured by cardiovascular magnetic resonance is impaired in chronic users of DMPA, and hypoestrogenism may be the mechanism of action. DMPA might adversely affect cardiovascular health, and in particular its use in women with cardiovascular disease should be additionally evaluated.

Adult↗

No association of menopause and hormone replacement therapy with carotid artery intima-media thickness. Atherosclerosis Risk in Communities (ARIC) Study Investigators.

BACKGROUND: Cardiovascular disease is the major cause of death in older women. Information on the relation of menopause and hormone replacement therapy with carotid atherosclerosis is limited. METHODS AND RESULTS: We examined cross-sectionally the association of menopausal status, years since last menstruation, and hormone replacement therapy status with carotid artery intima-media thickness as determined by B-mode ultrasound. Female participants (n = 5436) in the Atherosclerosis Risk in Communities Study without a history of symptomatic cardiovascular disease were included in the analyses. Menopause status in 45- to 54-year-old women who had never used hormone replacement therapy was not strongly associated with carotid intima-media thickness (mean = 0.65 mm and 0.67 mm in premenopausal and postmenopausal women, respectively, adjusted for age, race, cigarette years of smoking, body mass index, sport index, systolic blood pressure, use of blood pressure medications, drinking status, diabetes, and education level). In postmenopausal women aged 55 to 64 years, women with < or = 5 years since last menstruation had an adjusted average intima-media thickness (0.74 mm) comparable to those with > 5 years since last menstruation (0.75 mm) (P > .05). Although hormone replacement therapy use was associated with a more favorable lipid and hemostasis profile than nonuse, its use was not associated with intima-media thickness in postmenopausal women aged 55 to 64 years (adjusted average = 0.74 mm for current users of estrogen alone and approximately 0.75 mm each for current users of estrogen plus progestin, former users, and never users). CONCLUSIONS: The data suggest that the well-known associations of hormone replacement therapy with reductions in atherosclerotic cardiovascular disease may be attributable more to acute physiological effects, such as hemodynamic changes or reduced thrombosis, than to atherosclerosis itself.

Carotid Arteries↗