The Menstrual Cycle and Human Performance: An Overview

Physiological events during the normal menstrual cycle are determined by feedback loops within the hypothalamic-pituitary-ovarian axis. Hormonal changes within the menstrual cycle have potential impact on human performance. Relevant stages to consider are pre-menses and menses, the follicular and luteal phases separated by an abrupt elevation in lutenizing hormone and characterised by a sharp rise in body temperature coinciding with ovulation. Strenuous athletic training may affect the normal menstrual cycle. Such disruptions include delayed menarche in ballet dancers and gymnasts, shortened luteal phase and secondary amenorrhea associated with high training loads and competitive stress. Amenorrhea is also noted in flight attendants, linked with an inhibiting effect of disrupted circadian rhythm on lutenizing hormone. The so-called 'athlete triad' considers secondary amenorrhea, abnormal eating behaviour and osteoporosis (attributed to chronic hypoestrogenia). The normal cycle may also be disrupted when circadian rhythms are disturbed, for example in rapid time-zone transitions. Fluctuations in the steroid hormones have been associated with changes in muscle strength. There is evidence also of elevations in heart rate: changes may be partly specific to time of day. Effects on muscle strength may be determined at selected stages of the menstrual cycle, using whole-body performance, local muscle groups or isolated individual muscles. Whilst oestrogen has been implicated in the ergogenic effect of steroid hormones, there is accumulating evidence that a role for progesterone cannot be discounted. The isolation of the ovarian hormones separately is feasible with studies of IVF patients or groups on hormone replacement therapy.     

Rhythms in the ovulatory cycle. 3rd: Cortisol and dehydroepiandrosterone sulphate (DHEA-S)

The circadian profiles of cortisol and dehydroepiandrosterone sulphate (DHEA-S) were analyzed in a homogeneous group of 15 young normally cycling women, at 4 times of the menstrual cycle: early follicular (EF), late follicular (LF), early luteal (EL) and late luteal (LL) stages. The circatrigintan variations of the same hormones were also evaluated. Population-mean cosinor analysis allowed the demonstration of a highly significant circadian periodicity for both variables in any of the 4 stages of the menstrual cycle; on the other hand, the same computation failed to demonstrate a significant circatrigintan periodicity. In each of the stages considered, the circadian acrophase of DHEA-S was delayed in comparison to that of cortisol, being located in the early afternoon hours. The demonstration of a clear-cut circadian oscillation in serum DHEA-S prompts studies on possible chrono-abnormalities of the steroid production in women with hyperandrogenic diseases.     

Rhythms in the ovulatory cycle. 2nd: LH, FSH, estradiol and progesterone

The circadian profiles of LH, FSH, estradiol and progesterone were compared in a homogeneous group of 15 young normally cycling women, at 4 well characterized times of the menstrual cycle: early follicular (EF), late follicular (LF), early luteal (EL) and late luteal (LL) stages. The circatrigintan profiles of the same hormones were also evaluated. Population-mean cosinor analysis failed to demonstrate a circadian periodicity of LH in any of the 4 stages of the menstrual cycle; a circadian rhythm for FSH was present only in the 2 luteal phases (EL, LL); the same type of rhythmicity was present for estradiol only in the late luteal stage; on the contrary, a highly significant circadian rhythm of progesterone was present in each of the 4 menstrual stages considered (EF, LF, EL and LL). Population-mean cosinor analysis showed a highly significant circatrigintan periodicity of LH and FSH with the acrophases respectively between -109 degrees and -181 degrees and between -74 degrees and -125 degrees. Circatrigintan rhythmicity was also present for estradiol (acrophases between -161 degrees and -245 degrees) and progesterone (acrophases between -246 degrees and -296 degrees).     

Circamensal Rhythmicity and Muscle Function: The Role of Reproductive Hormones in the Regulation of Strength

The human female menstrual cycle is characterised by fluctuations in reproductive and pituitary hormones which regulate the monthly release of an ovum for fertilisation. The circamensal changes in the hormonal milieu may influence exercise performance. The generation of maximal voluntary muscle strength, mediated by changes in the steroid hormones, has been the focus of recent research, particularly ergogenic effects of oestrogen. Peak force of the adductor pollicis, normalised for muscle size, has been reported mid-cycle in concert with the rise in oestrogen. The removal of an oestrogen and progesterone environment results in muscle weakness in humans and animals. These hormones decline concomitantly following natural ovarian failure (i.e., the menopause) and surgical extraction of the ovaries (i.e., bilateral oophorectomy). To overcome the problem of controlling for rapid cyclical changes in reproductive hormones across the menstrual cycle, and to isolate the effects of oestrogen when measuring strength, other models have been adopted. Treatment of in vitro fertilisation patients involves, in part, the down-regulation of gonadotropin releasing hormone receptors followed by up-regulation with exogenous pituitary hormones. This presents a very low and very high oestrogenic milieu while progesterone remains rel atively stable. Under these conditions, maximal strength of the first dorsal interosseus muscle has been unchanged. The rapid loss in strength observed post-menopause is preserved, and possibly restored, in women taking hormone replacement therapy. These findings are significant for the preservation of skeletal and muscular health of post-menopausal women. There is increasing evidence to support the role of reproductive hormones in the regulation of muscle strength. Since the link between the hormone milieu during the menstrual cycle and strength changes is weak, other models must be employed. Strength declines rapidly at the menopause, and offsetting muscle weakness in post-menopausal women has implications in reducing the risk of muscloskeletal injury. Female athletes who are prone to amenorrhoea constitute another target group. A hormone-deficient state may not be beneficial to performance, but may compromise muscle function.     

Circamensal Rhythmicity and Muscle Function: The Role of Reproductive Hormones in the Regulation of Strength

The human female menstrual cycle is characterised by fluctuations in reproductive and pituitary hormones which regulate the monthly release of an ovum for fertilisation. The circamensal changes in the hormonal milieu may influence exercise performance. The generation of maximal voluntary muscle strength, mediated by changes in the steroid hormones, has been the focus of recent research, particularly ergogenic effects of oestrogen. Peak force of the adductor pollicis, normalised for muscle size, has been reported mid-cycle in concert with the rise in oestrogen. The removal of an oestrogen and progesterone environment results in muscle weakness in humans and animals. These hormones decline concomitantly following natural ovarian failure (i.e., the menopause) and surgical extraction of the ovaries (i.e., bilateral oophorectomy). To overcome the problem of controlling for rapid cyclical changes in reproductive hormones across the menstrual cycle, and to isolate the effects of oestrogen when measuring strength, other models have been adopted. Treatment of in vitro fertilisation patients involves, in part, the down-regulation of gonadotropin releasing hormone receptors followed by up-regulation with exogenous pituitary hormones. This presents a very low and very high oestrogenic milieu while progesterone remains rel atively stable. Under these conditions, maximal strength of the first dorsal interosseus muscle has been unchanged. The rapid loss in strength observed post-menopause is preserved, and possibly restored, in women taking hormone replacement therapy. These findings are significant for the preservation of skeletal and muscular health of post-menopausal women. There is increasing evidence to support the role of reproductive hormones in the regulation of muscle strength. Since the link between the hormone milieu during the menstrual cycle and strength changes is weak, other models must be employed. Strength declines rapidly at the menopause, and offsetting muscle weakness in post-menopausal women has implications in reducing the risk of muscloskeletal injury. Female athletes who are prone to amenorrhoea constitute another target group. A hormone-deficient state may not be beneficial to performance, but may compromise muscle function.     

月经周期对女性睡眠-觉醒和静息-活动的影响

目前有关月经周期对睡眠影响的研究结果并不一致,而对月经周期中昼夜睡眠-觉醒及静息-活动节律尚缺乏系统性的研究.本研究旨在观察正常育龄期女性月经周期中睡眠-觉醒及静息-活动昼夜节律的变化.我们采用静息-活动监测仪(actigraphy)和睡眠日志,调查了12个自然生活状态下健康育龄期妇女在月经周期不同阶段,即行经期、围排卵期、黄体早期及黄体晚期中睡眠与活动节律的变化.结果显示,睡眠-觉醒节律参数在四期之间无统计学显著差异;而静息-活动节律方面,所有受试女性静息-活动节律的平均日周期长度为(24.01±0.29)h,并且四期之间无显著性差异.行经期日间稳定系数(interdaily stability,IS)比黄体早期显著增加(P＜0.05).黄体早期日间活动开始时间明显较黄体晚期提前(P＜0.05);黄体早期的活动峰值时相比围排卵期显著提前(P＜0.05).月经周期可以影响静息-活动昼夜节律时相.而总体静息-活动数量与质量未发生显著变化;健康育龄期妇女在月经周期的各阶段中睡眠-觉醒节律亦无明显变异.     

Morphometric and hormonal changes during the chimpanzee menstrual cycle

BACKGROUND: Sex steroids affect many peripheral tissue sites in female mammals. Receptors for these hormones have been found in skin, fat, and bone. In women, these tissues can show morphological changes during the menstrual cycle that may be directly related to steroid secretion. METHODS: The present study was done on chimpanzees to document morphometric markers associated with these tissues (anogenital swelling volume, skin fold thickness as indicator of subcutaneous fat, bony diameters of mandible, wrist, and elbow) and to compare them with cyclic patterns of estradiol, progesterone, testosterone, gonadotropins, and prolactin. RESULTS: Swelling volume changed significantly over the menstrual cycle. All other morphometric parameters showed variation without statistical significance. Skin folds were thickest during the luteal phase. Bony diameters displayed similar but less distinctive changes. Testosterone correlated positively with diameter sites, inversely with subcutaneous fat. No relationships with either estradiol or progesterone were found. We assume that subcutaneous fat and morphometric bone parameters exhibit cycle-dependent changes that may be caused by changes in steroid secretion.     

Characterization and localization of estrogen and progesterone receptors of human fallopian tube

The cellular distribution of estrogen and progesterone receptors (ER and PR) in the human fallopian tube was investigated by immunohistochemical localization with specific monoclonal antibodies. Nuclear immunostaining was observed. Intense PR immunostaining was seen in tissues obtained at mid cycle and luteal stages of the normal menstrual cycle. On the other hand, enhanced staining for ER was seen in early follicular phase and mid cycle. Menopausal tissues showed negligible staining for both ER and PR. The ER and PR were characterized for their molecular size, anatomical distribution and levels during the menstrual cycle and in menopause. ER protein was present throughout the cycle and also during menopause. Western blot analysis revealed two forms of ER approximately 66 kDa and a truncated from approximately 49 kDa in hFT. Presence of A [approximately 90 kDa] and B [approximately 120 kDa] isoforms of human PR was detected. Follicular and early luteal tissue possessed relatively high concentration of immunoreactive PR whereas it was almost undetectable in menopausal tissues. These results suggests that ER and PR are regulated by the changing ovarian steroid hormones.     

Pulsatility of serum LH in pathological conditions

LH pulsatility changes throughout the normal menstrual cycle. The number of LH pulses increases during the first days after menstruation, remains unchanged thereafter until after ovulation and declines progressively during the luteal phase. LH pulse amplitude is highest during midcycle. In hypothalamic amenorrhea, gonadotropin levels are reduced. This appears to be a consequence of a reduction of hypothalamic Gn-RH secretion which is reflected by a diminished frequency and amplitude of LH pulses during the 24-hour span. Administration of an opiate antagonist, naloxone, increases LH pulse frequency in those patients, and in patients with secondary hypothalamic amenorrhea the daily oral administration of naltrexone, another specific opiate antagonist, induces ovulatory cycles. Patients suffering from hyperandrogenemia may present with eumenorrhea, oligomenorrhea or amenorrhea. There is an increase in mean LH levels and of the LH/FSH ratio with increasing severity of the ovarian disturbance. The increase in mean LH levels is a consequence of an increase in LH pulse amplitude while LH pulse frequency is not changed compared to the early follicular phase of the menstrual cycle.     

The role of the adenylyl cyclase system in the regulation of corpus luteum function in the human and in nonhuman primates

We have reviewed the properties of luteinizing hormone/human chorionic gonadotropic (LH/hCG)-sensitive adenylyl cyclase (AC) of human corpus luteum (CL) and its regulation by several hormones and nonhormonal activators. We have also described the changes in enzyme activity in membrane preparations of human and cynomolgus monkey CL obtained at various stages of the menstrual cycle and pregnancy. The data have been analyzed with respect to the functional status of the luteal tissue and to the species differences among primate CL. In the menstrual cycle, luteal AC responsiveness to LH/hCG was detectable during the midluteal phase, but not during the late luteal phase or in the follicular phase of the following cycle. In addition, nonhormonal stimulation was high in CL obtained during the midluteal and late luteal phases, but declined drastically by the follicular phase of the next cycle. In early pregnancy, the enzyme was unresponsive to LH/hCG stimulation, yet its sensitivity to nonhormonal stimulation was similar, if not identical, to that of midluteal phase CL. Functional activity was also evident at the end of pregnancy. These results demonstrate that expression of AC activity in primate luteal membrane changes significantly with varying hormonal status under physiologic conditions. It is concluded that the AC system in luteal membranes is an effective model to study the mechanisms that regulate function and life span of the human and nonhuman primate CL.     

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.     

Effects of progesterone receptor blockers on human granulosa-luteal cell culture secretion of progesterone, estradiol, and relaxin

We have developed culture methods for human luteinizing granulosa cells (GLC) that support the timely and dynamic secretion of estrogen (estradiol-17beta; E(2)), progesterone (P(4)), and relaxin (Rlx) in patterns that mimic serum hormone concentrations during the luteal phase of the menstrual cycle. Additional hCG, to simulate rescue of the corpus luteum, prevented the normal decline in GLC hormone production. To test the importance of the P(4) receptor in P(4) production, GLC were treated in vitro with two P(4) receptor antagonists. Human GLC received one of two hCG support protocols: a Baseline group simulating the normal luteal phase or a Rescue group simulating early pregnancy. Baseline and Rescue groups were treated with either RU-486 or HRP2000 either early or late in the cell culture period. The effects of treatments or control on ovarian steroid and peptide hormone production were determined (significant difference was P < 0.05). In the Rescue group, late treatment resulted in an immediate and dramatic decline in E(2), P(4), and Rlx secretion to nearly nondetectable levels within 1 day after treatment, and hormones remained depressed for the remaining 10 days of culture. In contrast, early treatment resulted in a decline in steroid hormone secretion that returned to control levels within 5 days of cessation of treatment, and Rlx secretion was delayed for approximately 5 days more than in controls. The data support the hypothesis that P(4) may be a required autocrine factor, not only for its own production but also for the maintenance of full endocrine function of the corpus luteum.     

Features of cardiovascular functioning during different phases of the menstrual cycle

The purpose of the present study was to determine whether there is a menstrual cycle effect on heart rate, blood pressure and heart rate variability. 10 healthy regularly cycling females (age 19-23 years) were studied during the follicular phase and luteal phase over two month. We found significant changes in heart rate, AMo and stress index during the menstrual cycle with a minimum in the follicular phase and maximum in the luteal phase. The HF and LF components decreased more during the luteal phase than during the follicular phase (p < 0.05), whereas a tendency for increase LF/HF was observed in the luteal phase. In the follicular phase SDNN, pNN50, Mo, MxDMn were significantly higher than in the luteal phase. Furthermore, the VIK was higher in the luteal phase compared to the follicular phase (p = 0.003). Blood pressure did not show any significant change during both these phases of the menstrual cycle. These findings indicate that sympathetic nervous activity in the luteal phase is greater than in the follicular phase, whereas parasympathetic nervous activity is predominant in the follicular phase. A difference of the balance of ovarian hormones may be responsible for these changes of autonomic functions during the menstrual cycle.     

Redistribution of adhering junctions in human endometrial epithelial cells during the implantation window of the menstrual cycle

The human uterine epithelium is characterised by remarkable plasticity with cyclic changes in differentiation that are controlled by ovarian steroid hormones to optimise conditions for embryo implantation. To understand whether and how cell-cell adhesion is affected, the localisation of junction proteins was studied throughout the menstrual cycle. Expression patterns were examined by immunofluorescence in 36 human endometrial specimens of different cycle stages. Antibodies against the desmosomal proteins desmoplakin 1/2 (Dp 1/2) and desmoglein 2 (Dsg 2), the adherens junction proteins E-cadherin and β-catenin and also the common junctional linker protein plakoglobin showed a strong subapical staining during the proliferative phase until the early luteal phase (day 20). In the mid- to late luteal phase, however, these junctional proteins redistributed over the entire lateral plasma membranes. In contrast, tight junction proteins (ZO-1, claudin 4) remained at their characteristic subapical position throughout the menstrual cycle. mRNA levels of Dp 1/2, E-cadherin and ZO-1 obtained by real time RT-PCR were not significantly changed during the menstrual cycle. The observed redistribution of desmosomes and adherens junctions coincides with the onset of the so called implantation window of human endometrium. We propose that this change is controlled by ovarian steroids and prepares the endometrium for successful trophoblast invasion.     

Pilot Investigation of the Circadian Plasma Melatonin Rhythm across the Menstrual Cycle in a Small Group of Women with Premenstrual Dysphoric Disorder

Women with premenstrual dysphoric disorder (PMDD) experience mood deterioration and altered circadian rhythms during the luteal phase (LP) of their menstrual cycles. Disturbed circadian rhythms may be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP) and LP of the menstrual cycle, consisting of intensive physiological monitoring under “unmasked”, time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P≤.03) worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P = .025) increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (P<.05) decreased melatonin at circadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed.     

Reexamination of testosterone, dihydrotestosterone, estradiol and estrone levels across the menstrual cycle and in postmenopausal women measured by liquid chromatography-tandem mass spectrometry

Measuring serum androgen levels in women has been challenging due to limitations in method accuracy, precision sensitivity and specificity at low hormone levels. The clinical significance of changes in sex steroids across the menstrual cycle and lifespan has remained controversial, in part due to these limitations. We used validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays to determine testosterone (T) and dihydrotestosterone (DHT) along with estradiol (E2) and estrone (E1) levels across the menstrual cycle of 31 healthy premenopausal females and in 19 postmenopausal females. Samples were obtained in ovulatory women in the early follicular phase (EFP), midcycle and mid luteal phase (MLP). Overall, the levels of T, DHT, E2 and E1 in premenopausal women measured by LC-MS/MS were lower overall than previously reported with immunoassays. In premenopausal women, serum T, free T, E2, E1 and SHBG levels peaked at midcycle and remained higher in the MLP, whereas DHT did not change. In postmenopausal women, T, free T, SHBG and DHT were significantly lower than in premenopausal women, concomitant with declines in E2 and E1. These data support the hypothesis that the changes in T and DHT that occur across the cycle may reflect changes in SHBG and estrogen, whereas in menopause, androgen levels decrease. LC-MS/MS may provide more accurate and precise measurement of sex steroid hormones than prior immunoassay methods and can be useful to assess the clinical significance of changes in T, DHT, E2 and E1 levels in females.     

Serum creatine kinase activity varies with ovulatory status in regularly exercising, premenopausal women

BACKGROUND/AIMS: The clinical complications associated with an unopposed estrogen environment and luteal phase defects observed in exercising women prompted the examination of the relationship of exercise and endogenous ovarian steroids with serum creatine kinase (CK) activity. METHODS: Subjects (n = 34) were classified into three groups according to their exercise and menstrual status, sedentary and exercising ovulatory groups (SedOvul, ExOvul), and an exercising amenorrheic group (ExAmen). Daily urine samples were collected to assess urinary ovarian steroid exposure and menstrual status. Serum CK activity was assayed in each menstrual cycle of all subjects. RESULTS: Exercise increased serum CK activity in all exercising subjects (p < 0.01), but the increase was greater in amenorrheic women compared to ovulatory women (SedOvul: 33.0 +/- 3.4; ExOvul: 43.7 +/- 4.1; ExAmen: 54.4 +/- 3.6, p < 0.05). When the ovulatory women were further divided into those with normal steroid production (ExOvul subgroup) and those with a suppressed progesterone luteal phase environment (ExLPD), both the ExOvul (51.9 +/- 5.4 IU/l) subgroup and ExAmen group had higher serum CK activity (p < 0.05) than the ExLPD (36.6 +/- 5.2 IU/l) subjects or the sedentary controls. CONCLUSIONS: These data demonstrate the complex association between ovarian hormone status and the normal serum CK response to regular mechanical stress imposed by chronic exercise training.     

Effect of sex hormones on neuromuscular control patterns during landing.

The purpose of the study was to investigate the effects of sex hormones across menstrual cycle phases on lower extremity neuromuscular control patterns during the landing phase of a drop jump. A repeated-measures design was utilized to examine sex hormone effects in 26 recreationally active eumenorrheic women. Varus/valgus knee angle and EMG activity from six lower extremity muscles were recorded during three drop jumps from a 50 cm platform in each phase of the menstrual cycle. Blood assays verified sex hormone levels and cycle phase. The semitendinosus muscle exhibited onset delays (p0.006) relative to ground contact during the luteal phase, and demonstrated a significant (p0.05) difference between early and late follicular phases. Muscle timing differences between the gluteus maximus and semitendinosus were decreased (p0.05) in the luteal compared to early follicular phases. These results suggest a different co-contractive behavior between the gluteus maximus and semitendinosus, signifying a shift in neuromuscular control patterns. It appears that female recreational athletes utilize a different neuromuscular control pattern for performing a drop jump sequence when estrogen levels are high (luteal phase) compared to when they are low (early follicular phase).     

The role of luteal steroid hormones in the regulation of the estrous cycle of high fecundity Olkuska sheep

The study was undertaken to investigate the steroid hormone production by sheep luteal cells. Corpora lutea were collected from 30 Olkuska sheep on Days 3, 6, 9, 12 and 15 of the estrous cycle during the reproductive season. In Experiment 1, steroid hormone concentration was estimated in extracts of CL. In Experiment 2, luteal cells were cultured in vitro for 24 h. Luteal cells isolated on Days 9 and 12 secreted high amounts of progesterone and androgens but smaller amounts of estradiol. Concentration of these steroids in CL extracts collected on the same days showed the same trend. In CL harvested on Day 15, a decrease in androgens and progesterone as well as a significant increase in estradiol were observed in culture media and in extracts. Judging from the high amounts of estradiol and low amounts of androgen observed at the end of the luteal phase, we speculate that the steroid hormones secreted by the regressing CL may play an active role in the regulation of the estrous cycle in the Olkuska sheep with autocrine influence on the luteal activity or a possible paracrine action on follicular growth.In the third Experiment, the possibility of heterogeneity in the multiple corpora lutea population of prolific Olkuska sheep was investigated. Differences were found in the level of progesterone and estradiol secretion by individual corpora lutea recovered from the same animal, which also varied in terms of weight. This is the first study which shows the existence of intra-ovarian and individual heterogeneity between corpora lutea recovered from ewes during the normal estrous cycle.