scholarly journals Twice-Daily Subcutaneous Injection of Kisspeptin-54 Does Not Abolish Menstrual Cyclicity in Healthy Female Volunteers

2013 ◽  
Vol 98 (11) ◽  
pp. 4464-4474 ◽  
Author(s):  
C. N. Jayasena ◽  
A. N. Comninos ◽  
G. M. K. Nijher ◽  
A. Abbara ◽  
A. De Silva ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Reproductive Function ◽  
Reproductive Hormones ◽  
Follicular Phase ◽  
Hypothalamic Amenorrhea ◽  
Healthy Women ◽  
Lh Pulsatility ◽  
Serum Lh ◽  
Healthy Female ◽  
Ultrasound Parameters

Background: Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously. Aim: Our aim was to determine the effects of follicular-phase kisspeptin-54 treatment on menstrual cyclicity in healthy women. Methods: We performed a prospective, single-blinded, 1-way crossover study. Healthy women received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline during menstrual days 7–14 (n = 5 per treatment arm). Serial assessments of basal reproductive hormones, ultrasound parameters, LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were performed. Results: Menstrual cyclicity persisted in all women after follicular-phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish acute stimulation of LH after injection of kisspeptin-54 or GnRH. In addition, kisspeptin-54 treatment was associated with a shorter mean length of the menstrual cycle (mean length of menstrual cycle was 28.6 ± 1.4 days with saline vs 26.8 ± 3.1 days with kisspeptin, P < .01), earlier onset of highest recorded serum LH (mean menstrual day of highest LH was 15.2 ± 1.3 with saline vs 13.0 ± 1.9 with kisspeptin, P < .05), and earlier onset of the luteal phase (mean menstrual day of progesterone increase was 18.0 ± 2.1 with saline vs 15.8 ± 0.9 with kisspeptin, P < .05). Conclusion: Our data suggest that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women. Further work is needed to determine whether kisspeptin could be used to treat certain anovulatory disorders.

scholarly journals The Effects of Kisspeptin-10 on Reproductive Hormone Release Show Sexual Dimorphism in Humans

2011 ◽  
Vol 96 (12) ◽  
pp. E1963-E1972 ◽  
Author(s):  
Channa N. Jayasena ◽  
Gurjinder M. K. Nijher ◽  
Alexander N. Comninos ◽  
Ali Abbara ◽  
Adam Januszewki ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Menstrual Cycle ◽  
Reproductive Hormones ◽  
Follicular Phase ◽  
Reproductive Hormone ◽  
Hormone Release ◽  
Men And Women ◽  
Healthy Men ◽  
Gonadotropin Release ◽  
Serum Lh

Abstract Background: Kisspeptin peptides are critical in human reproductive physiology and are potential therapies for infertility. Kisspeptin-10 stimulates gonadotropin release in both male and female rodents. However, few studies have investigated the effects of kisspeptin-10 on gonadotropin release in humans, and none have investigated the effect in women. If kisspeptin is to be useful for treating reproductive disease, its effects in both men and women must be established. Aim: To compare the effects of kisspeptin-10 administration on reproductive hormone release in healthy men and women. Methods: Intravenous bolus kisspeptin-10 was administered to men and women (n = 4–5 per group). Subcutaneous bolus and iv infusion of kisspeptin-10 was also administered to female women (n = 4–5 per group). Circulating reproductive hormones were measured. Results: In healthy men, serum LH and FSH were elevated after iv bolus kisspeptin-10, at doses as low as 0.3 and 1.0 nmol/kg, respectively. In healthy women during the follicular phase of the menstrual cycle, no alterations in serum gonadotropins were observed after iv bolus, sc bolus, or iv infusion of kisspeptin-10 at maximal doses of 10 nmol/kg, 32 nmol/kg, and 720pmol/kg/min, respectively. In women during the preovulatory phase, serum LH and FSH were elevated after iv bolus kisspeptin-10 (10 nmol/kg). Conclusion: Kisspeptin-10 stimulates gonadotropin release in men as well as women during the preovulatory phase of menstrual cycle but fails to stimulate gonadotropin release in women during the follicular phase. The sexual dimorphism of the responsiveness of healthy men and women to kisspeptin-10 administration has important clinical implications for the potential of kisspeptin-10 to treat disorders of reproduction.

Synergism between psychosocial and metabolic stressors: impact on reproductive function in cynomolgus monkeys

2007 ◽  
Vol 293 (1) ◽  
pp. E270-E276 ◽  
Author(s):  
Nancy I. Williams ◽  
Sarah L. Berga ◽  
Judy L. Cameron
Keyword(s):  
Psychosocial Stress ◽  
Reproductive Function ◽  
Diet Group ◽  
Reproductive Hormones ◽  
Hypothalamic Amenorrhea ◽  
Energy Imbalance ◽  
Cynomolgus Monkeys ◽  
Menstrual Cycles ◽  
Minor Stressors ◽  
Group 1

The role of energy imbalance versus psychosocial stress in the pathogenesis of female reproductive dysfunction characterized by anovulation and amenorrhea remains controversial. In women, functional hypothalamic amenorrhea can develop in the absence of significant weight loss, excessive exercise, or profound psychosocial disruption. We posited, therefore, that commonplace, seemingly minor stressors that alone would have minimal impact upon reproductive function might interact synergistically such that combinations of stressors would cause a greater impairment of the reproductive axis than any single stressor alone. We then developed a monkey model to test this hypothesis. Adult female cynomolgus monkeys with normal menstrual cycles were randomized into three experimental groups and studied over four menstrual cycles. The groups were: low-level psychosocial stress (i.e., moving to a new housing environment; Move, n = 8), moderate energy imbalance (Exercise + Diet, n = 9); and all stressors in combination (Move + Exercise + Diet, n = 10). Food intake, body weight, menstrual cyclicity, and reproductive hormones were assessed for two control menstrual cycles followed by two experimental cycles during which the monkeys experienced the stressors. Abnormal cycles were considered to be abnormally long or anovulatory cycles. Few abnormal cycles occurred in the Move group (1 of 8 monkeys) and in the Exercise + Diet group (1 of 9 monkeys). In contrast, 7 of 10 monkeys in the Move + Exercise + Diet group displayed at least one abnormal cycle (χ2 = 9.61, P = 0.008). These findings suggest that infertility due to hypothalamic hypogonadism can result from the combination of commonplace, seemingly minor stressors that often escape clinical attention.

scholarly journals Menstrual Cycle Dependent Variability for Serum Tumor Markers CEA, AFP, CA 19-9, CA 125 and CA 15-3 in Healthy Women

1999 ◽  
Vol 15 (4) ◽  
pp. 259-267 ◽  
Author(s):  
Ayşe Binnur Erbağci ◽  
Necat Yilmaz ◽  
Irfan Kutlar
Keyword(s):  
Menstrual Cycle ◽  
Tumor Markers ◽  
Normal Function ◽  
Ca 125 ◽  
Diagnostic Efficiency ◽  
Healthy Women ◽  
Healthy Female ◽  
Serum Cea ◽  
Cycle Dependent

Information on menstrual cycle dependent variation of tumor markers in healthy women is a subject of diagnostic efficiency and has an impact in elucidating the normal function of these markers. In this study midfollicular and midluteal concentrations of serum CEA, AFP, CA 19-9, CA 125, CA 15-3 and their relations with LH, FSH, prolactin, estradiol and progesterone were evaluated during ovulatory cycles in a group of 23 healthy female individuals. Samples were collected on the 7th and 21st day of the same menstrual cycle. Tumor marker and hormone concentrations were determined with chemiluminescence or electrochemiluminescence EIA methods. A significant phase-dependent difference was observed for CA 15-3, midluteal concentrations (mean ± SEM; 26.33 ± 1.56 U/ml) higher than the midfollicular (mean ± SEM; 19.27 ± 1.49 U/ml) concentrations (p < 0.001). But an obvious difference for other tumor markers investigated did not exist. Significant correlations of follicular and luteal CA 125 levels with body mass index of the subjects were observed (r:0.52, p < 0.05 and r:0.57, p < 0.005, respectively).CA 15-3 antigen is a product of the MUC-1 gene which is expressed in abundance by endometrial epithelial cells in the secretory phase of the menstrual cycle which may be the potential source of variability. The association of CA 125 levels with obesity suggests a possible role of adipose tissue in CA 125 metabolism. In conclusion our data suggest that in healthy women serum CA 15-3 levels are significantly elevated in the midluteal phase of the menstrual cycle compared to midfollicular phase. Therefore, consideration of menstrual cycle dependent variability for CA 15-3 appears indicated in interpretation of individual results.

Energy Balance and Reproductive Function in Active Women

2004 ◽  
Vol 29 (1) ◽  
pp. 48-58 ◽  
Author(s):  
Vicki J. Harber
Keyword(s):  
Menstrual Cycle ◽  
Energy Balance ◽  
Training Programs ◽  
Treatment Strategies ◽  
Reproductive Function ◽  
Negative Energy ◽  
Energy Availability ◽  
Menstrual Disorders ◽  
Improve Performance ◽  
Lh Pulsatility

Athletes engaged in rigorous training programs expend large amounts of energy and require appropriate energetic compensation to maintain or improve performance. If these exercise regimens are not fueled sufficiently, a negative energy balance will likely emerge and lead to a broad spectrum of menstrual cycle disturbances and less than optimal performance. This review examines the theory and evidence surrounding energy availability and reproductive function. Implications for performance and treatment strategies are also addressed. Key words: energy intake, energy expenditure, energy availability, menstrual disorders, LH pulsatility, amenorrhea

scholarly journals Pulsatile secretory characteristics of allopregnanolone, a neuroactive steroid, during the menstrual cycle and in amenorrheic subjects

2002 ◽  
pp. 347-356 ◽  
Author(s):  
AD Genazzani ◽  
M Luisi ◽  
B Malavasi ◽  
C Strucchi ◽  
S Luisi ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Luteal Phase ◽  
Pulse Amplitude ◽  
Follicular Phase ◽  
Neuroactive Steroid ◽  
Hypothalamic Amenorrhea ◽  
Temporal Coupling ◽  
Serum Gonadotropin ◽  
Hormonal Evaluation ◽  
Neuroendocrine Functions

OBJECTIVE: To investigate whether allopregnanolone, a neuroactive steroid involved in modulating behavioural and neuroendocrine functions, shows episodic secretion in eumenorrheic women, during the follicular and luteal phases of the menstrual cycle, and in women with stress-induced amenorrhea. PATIENTS: Six eumenorrheic women and 14 women with hypothalamic amenorrhea were enrolled for the present study. METHODS: All subjects underwent hormonal evaluation in baseline conditions and a pulsatility study to determine LH, cortisol and allopregnanolone episodic release. Eumenorrheic subjects were investigated twice, in the follicular phase (days 3-7) and in the luteal phase (days 18-22) of the menstrual cycle. LH, FSH, prolactin, estradiol, phosphate, DHEA, allopregnanolone and cortisol levels were evaluated in each case. RESULTS: In healthy women, serum gonadotropin and gonadal steroid levels were significantly lower (P<0.01 and P<0.05 respectively) than those in amenorrheic subjects. Allopregnanolone was higher in amenorrheic subjects and during the luteal phase, compared with the follicular phase, of eumenorrheic subjects (P<0.01). Pulse analysis revealed a significant episodic discharge of allopregnanolone in all subjects (follicular phase 6.5+/-0.3 peaks/6 h and luteal phase 5.5+/-0.4 peaks/6 h, hypothalamic amenorrhea 7.0+/-0.7 peaks/6 h) with higher pulse amplitude in amenorrheic subjects and during the luteal phase compared with the follicular phase of the eumenorrheic subjects (P<0.05). Moreover, the specific concordance index demonstrated that allopregnanolone is coupled with LH only during the luteal phase of the cycle and with cortisol during both phases. Allopregnanolone-cortisol coupling was also observed in amenorrheic subjects. CONCLUSIONS: Allopregnanolone is secreted episodically. Both the ovary and adrenal glands release this steroid hormone and it shows temporal coupling with LH only during the luteal phase, with cortisol during both the studied phases of the menstrual cycle in eumenorrheic women and again with cortisol in hypothalamic amenorrheic patients.

scholarly journals The Effects of Estrogen and Progesterone Hormones on Active Hip Joint Position Sense in Healthy Women in Different Phases of a Menstrual Cycle

2021 ◽  
Author(s):  
Maliheh Mosavi Ghomi ◽  
Mehrdad Shariati ◽  
Mokhtar Mokhtari ◽  
Fatemeh Ramezani Nowrozani
Keyword(s):  
Menstrual Cycle ◽  
Hip Joint ◽  
Position Sense ◽  
Joint Position Sense ◽  
Follicular Phase ◽  
Joint Position ◽  
Activity Increase ◽  
Healthy Women ◽  
Significant Difference ◽  
The Brain

Introduction: The proprioceptive system is a sensory system based on an individual’s knowledge of his or her body. This knowledge is transmitted to the brain through inputs received from joints, muscles, tendons, and ligaments. As a result, these inputs inadvertently inform the brain of the state of the body’s muscles. Numerous factors can affect this system. This study aimed to investigate the effect of estrogen and progesterone hormones on understanding and recognizing the proprioceptive sense of hip joint in healthy women during the menstrual cycle. Materials and Methods: In this quasi-experimental study, 15 healthy women participated voluntarily. They had regular menstrual cycles without any history of disease and drug use. The concentration of estrogen and progesterone during a cycle in the follicular (4-6 days), ovulation, and luteal phases were evaluated to detect their effects on the sense of perception and cognition of the proprioceptive joint in the two movements of abduction and flexion by the target angle reconstruction method (30°). Results: The errors of active joint position sense were reduced in abduction and flexion during ovular and luteal phases compared to the follicular phase. However, in the flexion direction of hip movement, there was a significant difference in absolute error during hormonal changes in the menstrual cycle (P=0.000). Conclusion: The results showed that due to more involvement of motor control of hip muscles joint by motor neuron activity (increase release of estrogen hormone), all errors reduced in ovular and luteal phases compared to the follicular phase. The flexion movement is more disturbed, and due to more flexibility in this direction, absolute errors are significantly reduced. This reduction of errors in ovular and luteal phases compared to the regular stage of hormone release (follicular phase) may cause some rigidity in the hip joint and an increase of trauma  in external mechanical forces. This study’s findings showed that the lowest proprioception sensation is in the follicular phase. Decreasing the concentration of sex hormones in this phase is likely to reduce the sense of recognition of the joint, thus increasing the likelihood of injury in this phase. Findings from this study showed that the lowest proprioceptic sensation is in  the follicular phase. The results of this study showed that the least sense is Prvpryvsptyk in Fazfvlykvlar.

Acute suppressive effect of ACTH-induced cortisol secretion on serum prolactin levels in healthy man

1982 ◽  
Vol 99 (3) ◽  
pp. 352-356 ◽  
Author(s):  
P. Bratusch-Marrain ◽  
H. Vierhapper ◽  
W. Waldhäusl ◽  
P. Nowotny
Keyword(s):  
Menstrual Cycle ◽  
Suppressive Effect ◽  
Prolactin Secretion ◽  
Follicular Phase ◽  
Serum Prolactin ◽  
Cortisol Secretion ◽  
Adrenocortical Insufficiency ◽  
Healthy Men ◽  
Healthy Women ◽  
Acute Increase

Abstract. The effect of ACTH on serum prolactin concentrations was studied in 6 healthy women in the follicular phase of the menstrual cycle, in 5 healthy men and in 6 patients (5 males, 1 female) with adrenocortical insufficiency. In healthy women prolactin levels decreased from basal, 14.4 ± 2.1 (SEM) μg/l to 9.4 ± 0.9 μg/l after 30 min and to 8.1 ± 0.7 μg/l after 60 min of iv administration of synthetic ACTH1-24 (0.25 mg). Upon continuous infusion of ACTH1-24 (0.25 mg for 8 h) prolactin fell to 4.4 ± 0.6 μg/l in healthy women and to 4.6 ± 1.5 μg/l (basal: 10.6 ± 1.8 μg/l) in healthy men. In patients with adrenocortical insufficiency prolactin concentrations remained unchanged following an 8 h infusion of ACTH1-24 (before ACTH: 14.5 ± 2.3 μg/l, after ACTH: 16.3 ± 3.1 μg/l). After treatment with dexamethasone (2 mg/day for 3 days) however, prolactin concentrations were suppressed both in healthy women (−52 ± 7%) and men (−25 ± 11%) and in patients with adrenocortical insufficiency (−21 ± 10%). Thus the effect of ACTH on prolactin appeared to be mediated via enhanced cortisol secretion. It is suggested that an acute increase in cortisol levels within the physiological range may modulate prolactin secretion.

Platelet Serotonin Pathway in Menstrual Migraine

Cephalalgia ◽  
1996 ◽  
Vol 16 (6) ◽  
pp. 427-430 ◽  
Author(s):  
L. Fioroni ◽  
G D'Andrea ◽  
M Alecci ◽  
A Cananzi ◽  
F Facchinetti
Keyword(s):  
Menstrual Cycle ◽  
Luteal Phase ◽  
Follicular Phase ◽  
Menstrual Migraine ◽  
Headache Attack ◽  
Blood Samples ◽  
Healthy Female ◽  
Hydroxyindoleacetic Acid ◽  
Mao Activity ◽  
Serotonin Pathway

In order to understand the possible 5-hydroxytryptamine (5HT) anomalies in migraine, particularly in the period before the headache attack, we compared the levels of 5HT, its stable metabolite 5-hydroxyindoleacetic acid (5HIAA) and platelet monoaminoxidase (MAO) activity in patients with menstrual migraine with those of healthy female controls. In every subject, blood samples were drawn during both follicular and late luteal phases of the menstrual cycle. In controls, platelet 5HT levels remained stable, whereas 5HIAA levels and MAO activity were higher in the luteal than in the follicular phase, suggesting an increased catabolism of 5HT which occurs physiologically just before menses. In menstrual migraine 5HIAA levels and MAO activity showed similar changes with higher values in the luteal than in the follicular phase. The luteal phase values were significantly higher than those of controls. Also, and in contrast to controls, 5HT levels decreased in the luteal phase. These data suggest that 5HT availability is reduced in menstrual migraine, possibly due to an increased catabolism and/or to a reduced synthesis, and hence predisposes patients to migraine attacks.

scholarly journals Endogenous Circadian Regulation of Female Reproductive Hormones

2019 ◽  
Vol 104 (12) ◽  
pp. 6049-6059 ◽  
Author(s):  
Shadab A Rahman ◽  
Leilah K Grant ◽  
Joshua J Gooley ◽  
Shantha M W Rajaratnam ◽  
Charles A Czeisler ◽  
...  
Keyword(s):  
Core Body Temperature ◽  
Premenopausal Women ◽  
Reproductive Function ◽  
Reproductive Hormones ◽  
Follicular Phase ◽  
Circadian Regulation ◽  
Plasma Estradiol ◽  
External Time ◽  
Core Body ◽  
Circulating Levels

Abstract Context Studies suggest that female reproductive hormones are under circadian regulation, although methodological differences have led to inconsistent findings. Objective To determine whether circulating levels of reproductive hormones exhibit circadian rhythms. Design Blood samples were collected across ∼90 consecutive hours, including 2 baseline days under a standard sleep-wake schedule and ∼50 hours of extended wake under constant routine (CR) conditions. Setting Intensive Physiological Monitoring Unit, Brigham and Women’s Hospital. Participants Seventeen healthy premenopausal women (22.8 ± 2.6 years; nine follicular; eight luteal). Interventions Fifty-hour CR. Main Outcome Measures Plasma estradiol (E2), progesterone (P4), LH, FSH, SHBG, melatonin, and core body temperature. Results All hormones exhibited significant 24-hour rhythms under both standard sleep-wake and CR conditions during the follicular phase (P < 0.05). In contrast, only FSH and SHBG were significantly rhythmic during the luteal phase. Rhythm acrophases and amplitudes were similar between standard sleep-wake and CR conditions. The acrophase occurred in the morning for P4; in the afternoon for FSH, LH, and SHBG; and during the night for E2. Conclusions Our results confirm previous reports of ∼24-hour rhythms in many female reproductive hormones in humans under ambulatory conditions but demonstrate that these hormones are under endogenous circadian regulation, defined as persisting in the absence of external time cues. These results may have important implications for the effects of circadian disruption on reproductive function.

scholarly journals Kisspeptin-54 Stimulates Gonadotropin Release Most Potently during the Preovulatory Phase of the Menstrual Cycle in Women

2007 ◽  
Vol 92 (10) ◽  
pp. 3958-3966 ◽  
Author(s):  
Waljit S. Dhillo ◽  
Owais B. Chaudhri ◽  
Emily L. Thompson ◽  
Kevin G. Murphy ◽  
Michael Patterson ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Bolus Injection ◽  
Random Order ◽  
Follicular Phase ◽  
Hpg Axis ◽  
Human Females ◽  
Healthy Female ◽  
Clinical Research Facility ◽  
Lh Release ◽  
G Protein Coupled

Abstract Context: Kisspeptin, the endogenous ligand of the G protein-coupled receptor 54, is a key regulator of the hypothalamo-pituitary-gonadal (HPG) axis. GPR54-null mice exhibit reproductive dysfunction, and exogenous kisspeptin potently stimulates the HPG axis in rodents, primates, and human males. The effects of kisspeptin administration to human females are unknown. Objective: Our objective was to investigate the effects of kisspeptin on LH release during the menstrual cycle in female volunteers. Design: Bolus sc kisspeptin-54 was administered to female volunteers, and plasma gonadotropins were measured. Setting: The study took place at a hospital clinical research facility. Volunteers: Subjects were healthy female volunteers with regular menstrual cycles. Intervention: 1) Volunteers received a sc bolus injection of kisspeptin-54 (0, 0.2, 0.4, 0.8, 1.6, 3.2, and 6.4 nmol/kg; n = 3–4 per dose) in the follicular phase; and 2) volunteers (n = 8) received a sc bolus injection of either kisspeptin-54 (0.4 nmol/kg) or saline in random order during each phase of the menstrual cycle. Main Outcome Measures: Plasma gonadotropins were measured. Results: 1) Kisspeptin-54 caused a dose-dependent increase in mean LH over time at doses from 0.2–6.4 nmol/kg. 2) Kisspeptin-54 increased plasma LH compared with saline injection in all phases of the cycle. The effect of kisspeptin was greatest in the preovulatory phase and least in the follicular phase of the cycle [mean increase in LH over baseline (IU/liter) ± sem for follicular phase was 0.12 ± 0.17; preovulatory phase, 20.64 ± 2.91 (P &lt; 0.001 vs. follicular phase); luteal phase, 2.17 ± 0.79 (P &lt; 0.01 vs. follicular phase)]. Conclusion: Elevation of plasma kisspeptin in human females potently stimulates LH release in the preovulatory phase and provides a novel mechanism for manipulation of the HPG axis in women.

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