Luteal phase of the menstrual cycle in young healthy women is associated with decline in interleukin 2 levels.

The aim of this study was to look at the possible changes in the blood levels of Interleukin 2 (IL2) during the sexual cycle in generally healthy, young, regularly menstruating women. The concentrations of progesterone and 17beta-estradiol were measured using radioimmunological assay. The bioactivity of interleukin 2 was measured using a biological test on the IL2-sensitive CTLL cell line. The percentage of lymphocytes with intracellular IL2 was determined by flow cytometry. Eighteen healthy volunteers (19-29 years old) were examined on days 5, 8, 14, 18 and 25 of the same cycle. All women were characterised by a regular menstrual cycle as per physiological levels of 17beta-es-tradiol and progesterone. The luteal phase of the cycle was characterised by both a decrease of IL2 blood levels and a decrease in the percentage of intracellular 1L2-containing lymphocytes stimulated in vitro. The IL2 level fluctuations observed during the menstrual cycle may be one factor causing pre-menstrual infections observed in young women. On the other hand, the decrease of IL2 may be seen as a start of the immune suppression necessary for an embryo's nidation.     

Body Temperature and Physical Activity Correlates of the Menstrual Cycle in Chacma Baboons (Papio hamadryas ursinus)

We investigated the temporal relationship between abdominal temperature, physical activity, perineal swelling, and urinary progesterone and estradiol concentrations over the menstrual cycle in unrestrained captive baboons. Using a miniature temperature‐sensitive data logger surgically implanted in the abdominal cavity and an activity data logger implanted subcutaneously on the trunk, we measured, continuously over 6 months at 10‐min intervals, abdominal temperature and physical activity patterns in four female adult baboons Papio hamadryas ursinus (12.9–19.9 kg), in cages in an indoor animal facility (22–25°C). We monitored menstrual bleeding and perineal swelling changes, and measured urinary progesterone and estradiol concentrations, daily for up to 6 months, to ascertain the stage and length of the menstrual cycle. The menstrual cycle was 36 ± 2 days (mean ± SD) long and the baboons exhibited cyclic changes in perineal swellings, abdominal temperature, physical activity, urinary progesterone, and estradiol concentrations over the cycle. Mean 24‐hr abdominal temperature during the luteal phase was significantly higher than during the periovulatory phase (ANOVA, F_{(2, 9)} = 4.7; P = 0.04), but not different to that during the proliferative phase. Physical activity followed a similar pattern, with mean 24‐hr physical activity almost twice as high in the luteal than in the periovulatory phase (ANOVA, P = 0.58; F_{(2, 12)} = 5.8). We have characterized correlates of the menstrual cycle in baboons and shown, for the first time, a rhythm of physical activity and abdominal temperature over the menstrual cycle, with a nadir of temperature and activity at ovulation. Am. J. Primatol. 74:1143‐1153, 2012. © 2012 Wiley Periodicals, Inc.     

Plasma Steroid and Luteinizing Hormone Levels during Prostaglandin F2α Administration in Luteal Phase of Menstrual Cycle

An intravenous infusion of prostaglandin F₂α (12.5-250μg/min) was administered in four volunteers in the mid-late luteal phase and three in the early luteal phase of the menstrual cycle.Frequent measurement of plasma progesterone, oestrogens, and luteinizing hormone (LH) showed that administration of high doses depressed plasma progesterone levels in the late luteal phase and caused concomitant side effects. Levels of progesterone in the early luteal phase were unaffected. In both phases oestrogen and LH levels were little altered. In two subjects, hourly progesterone levels measured throughout the day at a similar time in a subsequent control menstrual cycle showed an appreciable variation in one but steady levels in the second. This variation may contribute to the magnitude of the fall in progesterone noted during the infusion of prostaglandins.     

Hormonal control of endometrial glycogen metabolism in the Macaca arctoides

Endometrial biopsies obtained throughout the menstrual cycle of the Macaca arctoides show the glycogen content paralleling the serum progesterone fluctuations which occur during the menstrual cycle. Secretory phase samples contained a three-fold higher concentration of glycogen when compared to follicular phase tissue. Changes in the activity levels of the glycogen metabolizing enzymes, glycogen phosphorylase and glycogen synthetase, during various stages of the menstrual cycle are in accord with the concept that the post-ovulatory increase in endometrial metabolism is a function of progesterone influence on this tissue. Endometrial glycogen synthetase activity remains low during the early proliferative phase of the cycle and becomes significantly elevated (two-to three-fold) during the early secretory phase of the cycle. Glycogen phosphorylase shows a similar cyclicity later in the luteal phase, reaching maximal activity between the seventeenth to nineteenth day of the cycle and remaining elevated through the twenty-sixth day of the cycle. The coincident nature of the rise in peripheral progesterone to increases in uterine glycogen metabolism suggest that progesterone may be the prime modulator of uterine endometrial metabolism during the post-ovulatory phase.     

Pathogen disgust,but not moral disgust,changes across the menstrual cycle

The Compensatory Prophylaxis Hypothesis (CPH) proposes that during periods of increased susceptibility to infections, e.g., during the luteal phase of the menstrual cycle when progesterone suppresses immune function, women should feel more disgust toward pathogen cues and behave prophylactically. We investigate differences in disgust sensitivity and contamination sensitivity during different phases of the menstrual cycle in regularly cycling, healthy 93 rural and urban Polish women using the within-subject design. Disgust sensitivity was measured during two different phases of a menstrual cycle: 1) the follicular phase (the 5th or 6th day of the cycle) and 2) the luteal phase (on the 5th day after a positive ovulatory test or on 20th day of a cycle if the result of the ovulatory test was not positive). In the luteal phase, women scored higher on the Pathogen Disgust of the Three-Domain Disgust Scale, the Contamination Obsessions and Washing Compulsions Subscale of Padua Inventory, and on ratings of photographs showing sources of potential infections than in the follicular phase. Moral Disgust of the Three-Domain Disgust Scale did not differ between cycle phases. Hence, results suggest that women feel more disgusted toward cues to pathogens during the luteal phase, when susceptibility to infection is greater. We suggest that it is necessary to incorporate ovulatory testing as well as to conduct repeated measurements of disgust sensitivity in future tests of the CPH. Moreover, we believe that understanding how the feeling of pathogen disgust varies across the menstrual cycle and in relation to progesterone levels could be useful in designing effective infectious diseases prevention strategies for women.     

Effects of the menstrual cycle on auditory event-related potentials

Gonadal steroids (estradiol and progesterone) can alter neuronal functioning, but electrophysiological evidence in women is still sparse. Therefore, the present study investigated event-related potentials (ERPs) to neutral stimuli over the course of the menstrual cycle. In addition, associations between ERPs and salivary estradiol and progesterone concentrations were investigated. Eighteen young healthy women were tested at three different phases of their menstrual cycle (menses, and follicular and luteal phases). ERPs (i.e., the N1 and P2 components, reflecting cortical arousal and the orienting response, the N2, P3, and the Slow Wave (SW), reflecting controlled processing) were measured using two different paradigms. In the luteal phase, early ERPs reflecting the cortical arousal response were diminished in the first stimulus block indicating an attenuated orienting response. These changes were significantly correlated with estradiol as well as progesterone levels. As to the later ERP components, the N2 latency was shorter during menses compared to the other two phases. No menstrual cycle-associated changes were apparent in other late ERP components. In sum, this study documents changes in auditory ERPs across the menstrual cycle with the most prominent changes occurring during the luteal phase. Future ERP studies therefore need to be more attentive to the issue of menstrual phase when studying female subjects or female patients.     

Acetaminophen does not affect 24-h body temperature or sleep in the luteal phase of the menstrual cycle.

Body temperature and sleep change in association with increased progesterone in the luteal phase of the menstrual cycle in young women. The mechanism by which progesterone raises body temperature is not known but may involve prostaglandins, inducing a thermoregulatory adjustment similar to that of fever. Prostaglandins also are involved in sleep regulation and potentially could mediate changes in sleep during the menstrual cycle. We investigated the possible role of central prostaglandins in mediating menstrual-associated 24-h temperature and sleep changes by inhibiting prostaglandin synthesis with a therapeutic dose of the centrally acting cyclooxygenase inhibitor acetaminophen in the luteal and follicular phases of the menstrual cycle in young women. Body temperature was raised, and nocturnal amplitude was blunted, in the luteal phase compared with the follicular phase. Acetaminophen had no effect on the body temperature profile in either menstrual cycle phase. Prostaglandins, therefore, are unlikely to mediate the upward shift of body temperature in the luteal phase. Sleep changed during the menstrual cycle: on the placebo night in the luteal phase the women had less rapid eye movement sleep and more slow-wave sleep than in the follicular phase. Acetaminophen did not alter sleep architecture or subjective sleep quality. Prostaglandin inhibition with acetaminophen, therefore, had no effect on the increase in body temperature or on sleep in the midluteal phase of the menstrual cycle in young women, making it unlikely that central prostaglandin synthesis underlies these luteal events.     

Implicit motives and gonadal steroid hormones: effects of menstrual cycle phase,oral contraceptive use,and relationship status

Implicit motives for power and affiliation, salivary levels of testosterone, estradiol, and progesterone, and relationship status were measured in 18 normally cycling (NC) women, 18 women using oral contraceptives (OC), and 18 men at three assessments, corresponding to the menstrual, midcycle, and premenstrual phases of women's menstrual cycle. NC and OC women had elevated levels of affiliation motivation and decreased levels of power motivation at midcycle. Power motive changes were particularly pronounced in NC women across cycle phases. OC women and participants not engaged in an intimate relationship had significantly heightened levels of affiliation motivation, averaged across all cycle phases. Testosterone and power motivation, both averaged across all cycle phases, were positively correlated in men and in single women, but not in women engaged in an intimate relationship. Averaged levels of estradiol and power motivation were positively correlated in engaged women, but not in single women or men. Averaged levels of progesterone and affiliation motivation were negatively correlated in men, and there was evidence for a positive association between luteal affiliation motivation and periovulatory and luteal progesterone in NC women. This study therefore provides evidence that implicit motivational states fluctuate across the menstrual cycle, that the power motive is associated with testosterone and, in women, with estradiol, and that the affiliation motive and progesterone are associated in different ways in men and NC women.     

Estrogen receptor levels in the oviducts and endometria of cynomolgus macaques during the menstrual cycle

We sampled oviducts and endometria of 27 cynomolgus macaques during the menstrual cycle and measured the concentration of nuclear and cytoplasmic estrogen receptors in these tissues by exchange assay. We assessed the stage of the cycle by correlating serum estradiol (E2) and progesterone (P), as measured by radioimmunoassay, with the morphological condition of the ovaries, oviducts and endometrium of each animal. We have previously identified a series of oviductal stages that reflected the orderly sequence of cytological changes in the oviduct during the cycle, and we normalized receptor measurements to these stages. The amounts of nuclear and cytoplasmic estrogen receptor in both the oviduct and the endometrium were approximately twofold greater in the follicular phase than in the luteal phase. In the follicular phase, elevated receptor levels were associated with oviductal proliferation and differentiation, as well as with endometrial proliferation. During the luteal phase, lowered levels were correlated with atrophy and dedifferentiation in the oviduct, but with hypertrophy and progestational development in the endometrium. When the luteal phase of one cycle ends and the follicular phase of the next begins, it is a decline in serum P, not a rise in serum E2, that precedes the elevation in estrogen receptor level and the onset of proliferation in the oviduct and endometrium. Proliferation of the reproductive tract and elevations in nuclear estrogen receptor levels during the early follicular phase can therefore be viewed as consequences of the release of the system from antagonism by P.     

Opiatergic inhibition of pulsatile luteinizing hormone release during the menstrual cycle of rhesus macaques

The endogenous opioid peptides (EOPs) may inhibit the rate of hypothalamic gonadotropin-releasing hormone (GnRH) release and hence the frequency of pulsatile luteinizing hormone (LH) release, particularly in the luteal phase of the menstrual cycle. Our objectives were to compare the effects of an opiate antagonist, naloxone (NAL), on the patterns of LH, estradiol-17 beta (E2), and progesterone (P4) secretion during the follicular and luteal phases of the macaque menstrual cycle. Plasma levels of E2, P4, and bioactive LH were measured in serial, 15-min blood samples during 8-hr infusions of NAL (2 mg/hr) or saline, either on Days 5 or 6 of the follicular phase (FN and FS, n = 5 and 4, respectively) or on Days 8, 9, or 10 of the luteal phase (LN and LS, n = 5 each) of a menstrual cycle. The pulsatile parameters of each hormone were determined by PULSAR analysis and the correspondence of steroid pulses with those of LH were analyzed for each cycle stage in each animal. As expected, LH mean levels and pulse frequencies in LS monkeys were only about one-third of those values in FS animals. NAL had no effects on pulsatile LH, E2, or P4 release during the follicular phase. In contrast, luteal phase NAL infusions increased both LH mean levels and pulse frequencies to values which were indistinguishable from those in FS animals. LH pulse amplitudes did not differ among the four groups. Mean levels and pulse frequencies of P4 secretion in LS monkeys were about 4- and 14-fold greater than those values in FS animals. Mean levels and pulse amplitudes of P4 release in LN animals were greater than those values in all other groups. LH and E2 pulses were not closely correlated in follicular phase animals, and this pulse association was not altered by NAL. In FS monkeys, LH and P4 pulses were not correlated; however, NAL increased this LH-p4 pulse correspondence. LH and P4 pulses were closely correlated in luteal phase animals and this association was not affected by NAL. Our data suggest that the EOPs inhibit the frequency of pulsatile LH secretion in the presence of luteal phase levels of P4. During the midfollicular phase when LH pulses occur every 60 to 90 min, the opioid antagonist NAL alters neither the pulsatile pattern of LH release nor E2 secretion, but NAL may directly affect P4-secreting cells.     

17 β-hydroxysteroid dehydrogenase in monkey endometrium during the menstrual cycle and at the time of implantation

In order to further identify physiological similarities between 17β-hydroxysteroid dehydrogenase (HSD) in human and monkey endometrium, and to evaluate the role of estradiol-17β (E₂) oxidation to estrone (E₁) during periimplantation events, 30 rhesus monkeys were studied at different intervals of the nonfertile menstrual cycle (days 8, 12, 15, 18 and 24). Also, five pregnant monkeys provided endometrial tissue on day 24 of the fertile menstrual cycle, near the expected time of implantation. HSD activity in endometrium was low at midfollicular phase (day 8), increased to maximal levels (8-fold) during the periovulatory span (days 12 and 15),and was intermediate in mid to late luteal phase (days 18 and 24) in non-fertile menstrual cycles. In the absence of ovulation, HSD was low throughout. These enzyme data fit with a pattern of daily peripheral serum levels of E₂ and progesterone (P) and suggest that when the normal sequence of P follows elevated estrogens in late follicular phase, HSD activity is markedly enhanced in the early luteal phase. However, HSD activity in endometrium did not increase more in the fertile menstrual cycle, despite further elevations of serum P during rescue of the corpus luteum.     

Novel hyperprolactinemia and hyperprolactinemic anovulation model using the cynomolgus monkey (Macaca fascicularis)

We investigated the relationship between the menstrual cycle and hormone levels in cynomolgus monkeys, and developed a sulpiride-induced hyperprolactinemic anovulation model. On this study, we demonstrated the usefulness of the commercial human prolactin immunoradiometric assay kit for the measurement of cynomolgus monkey serum samples. In the normal menstrual cycle of the cynomolgus monkey, serum prolactin concentrations were not significantly different between luteal and follicular phases. However, the serum prolactin concentration tended to elevate at the ovulation stage. And serum progesterone began to increase after an estradiol surge, and then declined before the ensuing preovulatory rise in estradiol. During the luteal phase, the serum concentration of progesterone was elevated. Moreover, we aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in the cynomolgus monkey. The serum prolactin level gradually increased during the twice-daily administration of sulpiride, and the drug produced as big a response at 5 mg/kg. In this study, the length of the menstrual cycle was approximately 29 days in normal cynomolgus monkeys. When treatment with sulpiride had been continued for more than one month, serum progesterone and estradiol levels fell to within the range seen in the follicular phase of the normal cycle, and the absence of ovulation was recognized by laparoscopy. Moreover, in this period we found that amenorrhea or anovulatory menstruation in the experimental animals. We could produce an anovulatory model induced by sulpiride repeatedly administered over a long time period. Our findings suggest that the cynomolgus monkey is useful as a endocrinological model that uses prolactin as a parameter and as an anovulatory model; thus, it could be a useful model for the hyperprolactinemic amenorrhea and/or anovulation seen in humans.     

Dynamics of circulating concentrations of gonadotropins and ovarian hormones throughout the menstrual cycle in the bonnet monkey: role of inhibin A in the regulation of follicle‐stimulating hormone secretion

In higher primates, increased circulating follicle‐stimulating hormone (FSH) levels seen during late menstrual cycle and during menstruation has been suggested to be necessary for initiation of follicular growth, recruitment of follicles and eventually culminating in ovulation of a single follicle. With a view to establish the dynamics of circulating FSH secretion with that of inhibin A (INH A) and progesterone (P₄) secretions during the menstrual cycle, blood was collected daily from bonnet monkeys beginning day 1 of the menstrual cycle up to 35 days. Serum INH A levels were low during early follicular phase, increased significantly coinciding with the mid cycle luteinizing hormone (LH) surge to reach maximal levels during the mid luteal phase before declining at the late luteal phase, essentially paralleling the pattern of P₄ secretion seen throughout the luteal phase. Circulating FSH levels were low during early and mid luteal phases, but progressively increased during the late luteal phase and remained high for few days after the onset of menses. In another experiment, lutectomy performed during the mid luteal phase resulted in significant decrease in INH A concentration within 2 hr (58.3±2 vs. 27.3±3 pg/mL), and a 2‐ to 3‐fold rise in circulating FSH levels by 24 hr (0.20±0.02 vs. 0.53±0.14 ng/mL) that remained high until 48 hr postlutectomy. Systemic administration of Cetrorelix (150 µg/kg body weight), a gonadotropin releasing hormone receptor antagonist, at mid luteal phase in monkeys led to suppression of serum INH A and P₄ concentrations 24 hr post treatment, but circulating FSH levels did not change. Administration of exogenous LH, but not FSH, significantly increased INH A concentration. The results taken together suggest a tight coupling between LH and INH A secretion and that INH A is largely responsible for maintenance of low FSH concentration seen during the luteal phase. Am. J. Primatol. 71:817–824, 2009. © 2009 Wiley‐Liss, Inc.     

Effects of the menstrual cycle on muscle recruitment and oxidative fuel selection during cold exposure

Differences in core temperature and body heat content, generally observed between the luteal and follicular phase of the menstrual cycle, have been reported to modulate the thermogenic activity of cold-exposed women. However, it is unclear how this change in whole body shivering activity will influence fuel selection. The goal of this study was to quantify the effects of the menstrual cycle on muscle recruitment and oxidative fuel selection during low-intensity shivering. Electromyographic activity of eight large muscles was monitored while carbohydrate, lipid, and protein utilization was simultaneously quantified in the follicular and luteal phases of the menstrual cycle in nonacclimatized women shivering at a low intensity. The onset (～25 min), intensity (～15% of maximal voluntary contraction), and pattern (～6 shivering bursts/min) of the shivering response did not differ between menstrual cycle phases, regardless of differences in core temperature and hormone levels. This resulted in lipids remaining the predominant substrate, contributing 75% of total heat production, independent of menstrual phase. We conclude that hormone fluctuations inherent in the menstrual cycle do not affect mechanisms of substrate utilization in the cold. Whether the large contribution of lipids to total heat production in fuel selection confers a survival advantage remains to be established.     

Sex hormones correlated with sex skin swelling and rectal temperature during the menstrual cycle of the pigtail macaque (Macaca nemestrina).

Daily measurement of serum luteinizing hormone, estradiol-17beta, and progesterone were made during the menstrual cycle in nine pigtail macaques (Macaca nemestrina). All data were normalized to the day of the luteinizing hormone peak. Serum estradiol-17beta increased from approximately 100 pg/ml during the early follicular phase to 442 +/- 156 pg/ml during the maximum midcycle concomitant with the luteinizing hormone peak, and a small increase in serum estradiol-17beta was observed during the luteal phase coincident with the progesterone peak. Serum progesterone values increased slightly at the time of the luteinizing hormone peak and increased from 0.2-0.3 ng/ml during the midfollicular phase to peak levels of 8.3 +/- 1.75 ng/ml 9 days after the luteinizing hormone surge. Serum luteinizing hormone remained low and relatively constant throughout the early and midcycle, then sharply increased approximately four-fold to peak values of 6.25 +/- 0.9 ng/ml. Sex skin swelling increased slowly during the follicular phase and declined slowly throughout the early luteal phase. Rectal temperature did not change significantly throughout the menstrual cycle. The similarity of plasma sex hormone changes during the menstrual cycle between women and the pigtail macaque suggested that this nonhuman primate should be a useful animal model for studying human reproduction.     

Sexual behavior and hormone levels during the menstrual cycles of rhesus monkeys.

The sexual interactions of 10 pairs of rhesus monkeys were observed during a control and an experimental menstrual cycle of each female. During the experimental cycle the females were treated with an antiandrogen, flutamide. Daily peripheral serum levels of estradiol, testosterone, and progesterone in each female were determined by radioimmunoassay. Sexual behavior did not correlate reliably with female serum concentrations of any hormone measured nor with the menstrual cycle stage. Administration of the antiandrogen to the females did not affect the sexual behavior of the pairs, although female serum levels of estradiol and testosterone were reduced. It was concluded that although female ovarian hormones may influence rhesus sexual interactions under some circumstances, the normal hormonal fluctuations during the menstrual cycle need not regulate this behavior; a knowledge of an intact rhesus female's hormonal condition does not allow accurate predictions about behavior displayed during laboratory pair tests with a male.     

Effect of inhibition of estrogen synthesis during the luteal phase on function of the corpus luteum in rhesus monkeys

It has been hypothesized that estrogen synthesized by the corpus luteum initiates luteal regression during the nonfertile menstrual cycle in primates. To study the role of endogenous estrogens in functional regression of the monkey corpus luteum, we administered the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) to rhesus monkeys during the luteal phase of the menstrual cycle. Twice-daily oral administration of ATD suppressed systemic and intraluteal estrogen levels by 80-90%. The midluteal phase rise in estradiol concentrations that occurs in rhesus monkeys was completely abolished by ATD treatment. Despite suppression of estrogen synthesis during the luteal phase, mean menstrual cycle length and length of the luteal phase were not different than in control monkeys treated with vehicle only. Progesterone levels were lower in the ATD-treated group on the second and third day of treatment, but did not differ from control levels during the remainder of the cycle. These data suggest that elevated estrogen synthesis during the luteal phase of the menstrual cycle is not a prerequisite for spontaneous luteolysis in rhesus monkeys.     

Progesterone inhibits embryotoxic effect of the complement system

The complement system of normal human serum (NHS) manifests a strong, dose dependent embryotoxic potential when administered to chick embryos inducing, among others, also malformations of the brain. We have demonstrated, however, that the degree of complement-induced embryotoxicity varied remarkably in the course of the menstrual cycle of fertile healthy women, although the complement serum activity (CH100) exhibited no significant fluctuation. On the other hand, the variation of embryotoxicity appeared negatively associated with progesterone levels. Following our results high progesterone levels occurring physiologically in luteal phase of the menstrual cycle suppress the embryotoxic action of the complement system.     

The principles and the routes of progestagenes' administration in PCOS

One of the chief findings in polycystic ovaries syndrome may be the defective luteal phase of the menstrual cycle. There is a growing list of publications indicating a defective progesterone production by granulosa cells of ovarian follicles. In consequence, women with polycystic ovaries often require both the luteal phase and early pregnancy supplementation. From different routes of progesterone administration during the menstrual cycle, as the most clinically reliable in the early pregnancy either intramuscular or intravaginal route has been recommended.     

Inhibitory effect of progesterone in the postcastration gonadotrophin rise in women

This study was designed to investigate the effects of progesterone on the gonadotrophin rise after bilateral salpingo-oophorectomy (BSO). Twenty-eight regularly menstruating women underwent hysterectomy and BSO during the follicular phase of the menstrual cycle. They were divided into 5 groups depending on the treatment after BSO. Plasma LH and FSH were studied serially for 14 days after BSO and the patterns of LH and FSH rises were contrasted to those observed in the control group which received neither progesterone nor estrogen. LH and FSH levels in the group which were given low dose progesterone only, rose consistently after BSO and these patterns were similar to those seen in the control group. However, the addition of estrogen reduced gonadotrophin rises significantly more than estrogen did alone. Further, the luteal phase level of progesterone solely has a suppressive effect on the gonadotrophin rises after BSO. Our observations suggest that synergism of progesterone with estrogen may exist in suppressing gonadotrophin secretion in the normal luteal phase and should help in understanding why gonadotrophin levels in the luteal phase are lower than those in the follicular phase of the menstrual cycle.