Phase Of Ovarian Cycle Research Articles

A Regimen of Oral Contraceptives Restricted to the Periovulatory Period May Permit Folliculogenesis But Inhibit Ovulation

Increased safety of oral contraceptives (OC) has resulted from a reduction in the estrogen and progestin content per tablet. A reduction in the number of hormonally active pills and their placement at critical points within the cycle may provide a novel regimen for further reducing the hormonal content of OC per cycle and their attendant side effects without compromising efficacy. The objective of this study was to determine the effectiveness of two OC regimens that incorporate a delayed start and limited midcycle use of the combination of ethinyl estradiol and norethindrone, and limited use of norethindrone only during the second half of the cycle. Main outcome measures were defined as ovulation, serum concentrations of estradiol (E 2), luteinizing hormone (LH), follicle stimulating hormone (FSH), progesterone (P), follicular diameters, and endometrial thickness. Volunteers were issued blister packs containing 28 pills and randomized to one of two groups. Group 1 used a combination of 50 μg ethinyl estradiol and 1 mg norethindrone per tablet day 6–10, and 0.70 mg norethindrone only day 11–19. Placebo tablets were used on days 1–5 and day 20–28. Group 2 used a combination of 50 μg ethinyl estradiol and 1 mg norethindrone per tablet on day 8–12, and 0.70 mg norethindrone only on day 13–21. Placebo tablets were used on day 1–7 and day 22–28. A total of 20 cycles were studied using 10 volunteers. To assess any possible carryover effect, two successive cycles were studied for each subject. Serum sampling for E 2, FSH, LH, and P, and transvaginal ultrasound imaging to assess endometrial thickness and follicle diameter were carried out at 4 day intervals throughout the cycle. One ovulation occurred in 10 cycles in group 1. Five ovulations occurred in 10 cycles in group 2. All ovulations, regardless of group, occurred in the second cycle. Peak E 2 concentrations were not significantly different between groups (152.04 ± 107.1 pg/mL vs 162.1 ± 56.1 pg/mL [mean ± SD] for groups 1 and 2, respectively) but occurred earlier in the cycle in group 1. No differences were noted between the groups in serum concentrations of FSH or LH for any given cycle day. Maximum follicle diameters were not different between groups 1 and 2, regardless of ovulatory status (20.5 ± 8.1 mm 2 vs 20.6 ± 14.2 mm 2, respectively). Ultrasound imaging assessment of midcycle follicle growth revealed diameters ranging from 18.5 mm 2 to 34.0 mm 2 with gradual resolution through the second half of the cycle in anovulatory cycles, and 16.0 mm 2 to 23.5 mm 2 with abrupt disappearance in ovulatory cycles. Endometrial thickness did not exceed 10 mm for any anovulatory cycle regardless of group, but ranged from 6 to 9 and 6 to 11 during the luteal phase of ovulatory cycles of groups 1 and 2, respectively. Peak serum P concentrations at midluteal phase in ovulatory cycles ranged from 9.2 ng/ml to 18.2 ng/ml. Data from this preliminary study suggest that ovulation may be prevented with a combination of ethinyl estradiol and norethindrone started as late as cycle day 6 and limited to 5 days’ duration using norethindrone only for 9 days during the second half of the cycle. Such a restricted regimen may offer both an effective method of contraception and a means of further reducing both estrogen and progestin content per cycle and the possible short and long term adverse side effects of these hormones.

Transforming growth factor-beta inhibits progesterone-induced enkephalinase expression in human endometrial stromal cells.

The specific activity of enkephalinase in endometrial tissue of nonpregnant ovulatory women is correlated in a highly significant, positive manner with the plasma level of progesterone. The specific activity and levels of enkephalinase messenger ribonucleic acid and immunoreactive protein also are increased in human endometrial stromal cells in culture by treatment with a synthetic progestin, medroxyprogesterone acetate (MPA), in a time- and dose-dependent manner. From an analysis of the temporal relationship between the specific activity and half-life of enkephalinase in endometrial tissue and the level of progesterone in plasma, it appeared highly likely that some mechanism, in addition to progesterone withdrawal, was operative to reduce enkephalinase activity in endometrium during the late luteal phase of the ovarian cycle before progesterone levels had declined below those known to be effective for progesterone action. In stromal cells previously (and concurrently) treated with MPA (10(-9) mol/L), the addition of transforming growth factor-beta 1 (TGF beta 1) or TGF beta 2 (1 ng/mL) to the medium caused a decrease in enkephalinase specific activity despite the continued presence of MPA. The half-life of enkephalinase (activity) in stromal cells treated with MPA plus TGF beta 1 was 2.8 days, which is similar to the computed half-life for enkephalinase in endometrial tissue during the mid- to late secretory phase of the endometrial cycle (2.5 days). Simultaneous treatment of endometrial stromal cells with MPA (10(-9) mol/L) and TGF beta 1 (1 ng/ mL) prevented the progestin-induced increase in enkephalinase specific activity and immunoreactive enkephalinase protein. Thus, TGF beta acts to oppose the progesterone-induced increase in enkephalinase expression in endometrial stromal cells, even in the continued presence of MPA.

Energy intakes are higher during the luteal phase of ovulatory menstrual cycles

We compared energy and macronutrient intakes across the menstrual cycle in participants (n = 42) in a study that assessed the frequency of ovulatory disturbances in regularly cycling vegetarians and nonvegetarians. Women kept daily basal body temperature records for six consecutive menstrual cycles and provided 3-d diet records near the beginning, middle, and end of different cycles. On completion of the study, temperature records were quantitatively analyzed to determine whether cycles were ovulatory, and if so, the date the luteal phase began. Diet records kept near the beginning and end of cycles were matched with temperature analysis results, and women were grouped according to whether the end-of-cycle record was kept during the luteal phase of an ovulatory cycle (group 1, n = 29), or during an anovulatory cycle or before luteal phase onset of a short luteal phase cycle (group 2, n = 13). Group 1 had higher energy intakes during the luteal than during the follicular phase (9.27 +/- 2.69 vs 8.01 +/- 2.36 MJ/d, P < 0.0001), whereas intakes of group 2 did not differ across the cycle (7.91 +/- 2.18 vs 8.20 +/- 1.48 MJ/d, NS). Both groups' macronutrient intakes were similar in records kept near the beginning and end of cycles. Documentation of ovulation is necessary in studies assessing premenopausal women's energy intakes.

Strategies of ovarian function of importance to gynecologic investigations.

The purpose of this article was to examine the similarities and differences in ovarian morphology and function that are known to exist among mammalian species. The previous difficulties and present solutions to the characterization of ovarian function in non-domestic or non-laboratory species are discussed. The current literature regarding comparative ovarian structure and function was reviewed to identify examples of the diversity found with mammals. Major differences in ovarian anatomy include location in the body cavity; the degree of membranous covering surrounding the ovary; vascularization of the ovary, oviduct, and uterus; and the organization of different cell types within the ovary. The differences in ovarian function are simplified in this review by categorizing the known examples into six groups according to patterns in follicle growth and development, mechanisms of ovulation, response of steroid target cells, and luteal function. Each mammalian species has a unique expression of its ovarian function. The differences between species range from quantitative differences in ovarian cycle phase length to qualitative differences in cell type, endocrine activity, and mechanism of ovulation. These differences present a special problem to research scientists when they attempt to select models for studying many aspects of female reproduction.

The metabolic disposition of plasma 5 alpha-dihydroprogesterone (5 alpha-pregnane-3,20-dione) in women and men.

This study was conducted 1) to ascertain whether the high levels of plasma 5 alpha-dihydroprogesterone (5 alpha DHP) during the luteal phase of the human ovarian cycle and pregnancy are attributable to high rates of production or, alternatively, low rates of clearance, and 2) to estimate the relative distribution of the irreversible metabolism of 5 alpha DHP, i.e. hepatic compared with extrahepatic clearance of plasma 5 alpha DHP. The concentration of 5 alpha DHP in plasma of women during the luteal phase of the ovarian cycle and pregnancy is very high, viz. 12-40% that of progesterone. Thus, a potentially large source of steroid precursor is available for the formation of bioactive 5 alpha-pregnanolone metabolites. We found that the MCR of 5 alpha DHP in women and men is 4187 +/- 312 L plasma/24 h (range, 3181-5506; n = 6). The MCR of 5 alpha DHP as a function of body surface area was 2406 +/- 240 L/24 h.m2. The MCR of 5 alpha DHP, therefore, is the greatest of any steroid reported, except for that of the catechol estrogens, which are metabolized intravascularly by erythrocyte catechol-O-methyltransferase. Based on estimated rates of liver plasma flow (1500 L/24 h) and hepatic extraction (75-85%) of lipophilic steroids that are not specifically bound in plasma with high affinity to binding proteins as determined by other investigators (e.g. 5 alpha DHP), we estimate that approximately 1200 L plasma/24 h are cleared of 5 alpha DHP by liver and approximately 2800 L plasma/24 h are cleared of 5 alpha DHP (70%) by metabolism in extrahepatic tissues. Thus, 5 alpha DHP can serve as a precursor for bioactive 5 alpha-pregnanolone(s).

GABAA RECEPTORS AND ACTIONS OF NEUROSTEROIDS

GABA acting via GABAA receptors exerts inhibitory actions on neurons. Certain endogenous steroids (neurosteroids) are modulators of GABAA receptors. Tetrahydroprogesterone (THP) and tetrahydrodeoxycorticosterone (THDOC) behave as allosteric agonists of the GABAA receptors, while pregnenolone sulfate (PS) and dehydroepiandrosterone sulfate (DHEAS) act as antagonists. The neurosteroids alter ligand binding, chloride transport and electrophysiological responses to GABA, acting at unique steroid recognition sites at the GABAA receptors. Certain behavioral effects of the neurosteroids are consistent with their GABA-agonistic or -antagonistic properties. For example, THP and THDOC manifest hypnotic and anxiolytic actions, while PS reduces barbiturate-induced sleep time. Physiologically changing levels of GABAergic steroids, during development, stress, phases of ovarian cycle or pregnancy may alter GABAA receptor function, thus influencing neuronal excitability and CNS arousal. For example, pregnancy and puerperium are associated with alterations of GABAA receptor function that seem attributable to steroid actions. GABA-ergic steroids also regulate uterine contractibility. This phenomenon may play a role in quieting the uterus during pregnancy and in its activation during parturition. (Review: Majewska, Prog.Neurobiol.38:379, 1992.)

Protein kinase C in uterine and systemic arteries during ovarian cycle and pregnancy

Elevated uterine blood flow is associated with increases in local estrogen-to-progesterone ratios during the follicular phase of the ovarian cycle and late pregnancy. Because protein kinase C (PKC) activation increases arterial tone, decreased PKC activity may mediate vasodilation. Therefore, we determined uterine (UA) and systemic artery (SA, omental) PKC activity (pmol.mg protein-1.min-1) during the follicular (n = 6), early luteal (n = 4), and late luteal (n = 3) phases of the sheep ovarian cycle, and at 110 +/- 3 (n = 4) and 130 +/- 1 (n = 8) (+/- SE) days of ovine gestation. The stage of the ovarian cycle was verified by the presence of follicles (high estrogen) or corpora lutea (high progesterone) on the ovary and by plasma estrogen and progesterone concentrations. UA-PKC activity (pmol.mg protein-1.min-1) during the follicular phase was 100 +/- 18 and increased progressively to 155 +/- 28 during the early luteal phase and to 219 +/- 37 (P less than 0.05) during the late luteal phase; SA-PKC activity was unchanged. A local utero-ovarian relationship was observed, i.e., UA-PKC activity was lower (P less than 0.001) in UA ipsilateral to ovaries with only follicles (105 +/- 14) when compared with UA adjacent to ovaries with corpora lutea (224 +/- 26), which was similar to SA-PKC activity (184 +/- 35). UA-PKC activity fell from 344 +/- 70 at 110 days to 109 +/- 12 at 130 days gestation (P less than 0.05); SA-PKC activity was unchanged. During the ovarian cycle and latter one-third of ovine pregnancy, increased estrogen production is associated with decreased UA-PKC activity; thus local ovarian and placental steroids may alter PKC activity, thereby regulating UA tone and blood flow.

Evidence for a specific role of GnRH pulse frequency in the control of the human menstrual cycle

An adequate frequency of gonadotropin-releasing hormone (GnRH) pulses appears to be important for physiological gonadotropin secretion. However, limited information exists on the exact role of this parameter in the regulation of the human menstrual cycle. Thus we studied gonadotropin and gonadal steroid secretion in 32 women with primary hypogonadotropic amenorrhea who received pulsatile GnRH (60 to 120 micrograms/day) at 60- or 120-min intervals for a total of 64 ovulation induction cycles. Ovulation was achieved in 94% of 60-min and in 70% of 120-min cycles P less than 0.05). In the follicular phase of ovulatory cycles, estradiol (E2) levels did not differ among the four groups; however, mean luteinizing hormone (LH) levels were lower (P less than 0.005), and the midcycle LH surge was severely blunted in cycles of subjects receiving 120 micrograms/day (5 micrograms/bolus) GnRH every 120 min compared with subjects receiving the same dose of GnRH per day or per bolus every 60 min. Luteal progesterone (only in 60 micrograms/day GnRH cycles) and E2 levels were lower in 120-min than in 60-min cycles (P less than 0.05). The use of the higher daily GnRH dose (120 micrograms/day) reduced or abolished the frequency-associated hormone level differences. We conclude that a low frequency of pulsatile GnRH in women 1) decreases mean LH levels and blunts the midcycle gonadotropin surge, 2) does not increase follicle-stimulating hormone concentrations, and 3) is associated with a reduced rate of ovulation.

Ovarian cycle phase differences of endometrial macrophage- and lymphocyte subtypes

Ovarian cycle phase differences of endometrial macrophage- and lymphocyte subtypes

THE ROLE OF CHRONIC ANOVULATION IN THE POLYCYSTIC OVARY SYNDROME: NORMALIZATION OF SEX‐HORMONE‐BINDING GLOBULIN LEVELS AFTER CLOMIPHENE‐INDUCED OVULATION

A group of anovulatory patients with polycystic ovaries (PCO) was given clomiphene citrate and compared with three control groups: normal women having spontaneous, ovulatory cycles, patients with PCO having spontaneous, regular, ovulatory cycles, and anovulatory patients without PCO. Comparisons were made at precise points of the menstrual cycle (taking the day of ovulation as day 0), using ultrasound estimates of mean follicular diameter, uterine volume, and endometrial thickness, and biochemical measurements of LH, FSH, oestradiol (E2), testosterone (T), progesterone (P) and sex-hormone-binding globulin (SHBG). Before clomiphene treatment, the anovulatory patients with PCO had significantly lower levels of SHBG and higher follicular phase concentrations of LH than all three control groups. After two cycles of clomiphene-induced ovulation, the serum LH concentration fell significantly and levels of SHBG increased significantly to levels similar to those found in spontaneously ovulating women with normal ovaries. It is likely that the loss of the usual considerable rise in E2 in both the follicular and luteal phases of ovulatory cycles is the main reason for the low SHBG found in the PCO syndrome. The loss of the normal P-induced gonadotrophin suppression may be a factor in allowing LH levels to rise.

Role of ovarian steroids on the catecholamine synthesis and release in female rat adrenal: [formula omitted] and [formula omitted] studies

In a previous report, we described the existence of an effect of ovarian steroids on the adrenal medulla activities of the enzymes involved in catecholamine (CA) catabolism. To complete that study, we have now examined the adrenal medulla activity of tyrosine hydroxylase (TH), the rate limiting enzyme of the CA synthesis, as well as the in vitro release of CAs from incubated adrenal medullas. The study has been performed with adrenal medullas from female rats with physiological (estrous cycle) or pharmacological (steroid treatment) alterations in their circulating levels of estrogens and progesterone. The in vitro release of CAs from incubated adrenal medullas of estradiol-treated rats was lower than that obtained in vehicle-treated animals. In consequence, the preovulatory increase of estradiol would be the responsible of the low in vitro release of CAs observed during the estrous phase of ovarian cycle. However, this steroid does not seem to affect the CA synthesis, since the adrenal medulla activity of TH was not altered after the estradiol treatment nor during the estrous cycle. On the contrary, progesterone treatment increased TH activity 24 h after the steroid injection. This effect was independent of estradiol. However, an estrogen-dependent increase in TH activity occured short-time after the steroid administration. Although progesterone by itself failed to modify the in vitro release of both CAs, it was able to reverse the estradiol-induced decrease in epinephrine release. In summary, estradiol seems to decrease the ability of the adrenal medulla to release CAs to the peripheral blood. without affecting the CA synthesis, whereas progesterone mostly affects TH activity, being its effects temporary and partially depending on estrogens.

Eicosanoids in primary dysmenorrhea, endometriosis and menstrual migraine.

This paper summarizes what has been learned over the years about the role of eicosanoids in the pathogenesis of primary dysmenorrhea, endometriosis and menstrual migraine. The role of prostaglandins (PGs) in the pathogenesis of primary dysmenorrhea is inferred from four main observations: firstly, the clinical symptoms of primary dysmenorrhea are similar to those induced by the administration of PGF2 alpha and PGE2 for the induction of labour; secondly, the increased production of PGs by the endometrium during the luteal and menstrual phases of ovulatory cycles is consistent with the occurrence of primary dysmenorrhea mainly in ovulatory cycles; thirdly, the concentrations of PGF2 alpha and PGE2 in the endometrium and menstrual fluid of dysmenorrheic women are significantly higher than in controls; fourthly, certain PG inhibitors have been proved to be effective in the treatment of dysmenorrhea. The change in PG production can explain the major symptoms of primary dysmenorrhea, including the increased uterine contractility, uterine ischemia and the lowering of the pain threshold to chemical and physical stimuli in the pelvic nerve terminals. Moreover, recent experimental data suggest that leukotrienes (LTs) might be among the alternative pathogenetic causes of primary dysmenorrhea. The data which support a relationship between eicosanoids and endometriosis are as follows: endometriotic tissue produces PGs; the peritoneal fluid concentration of PGF2 alpha increases significantly after the induction of endometriosis in laboratory animals; the concentration of PGs in peritoneal fluid of some patients with endometriosis is greater than in controls and, finally, the number and activation of pelvic macrophages which are able to synthesize eicosanoids increase in patients with endometriosis. Possible roles for eicosanoids in the pathogenesis of infertility and secondary dysmenorrhea induced by endometriosis have been suggested. Eicosanoids are probably also involved in the pathogenesis of menstrual migraine. Different types of PGs might play a role both in the initial vasoconstriction during the prodromal phase of migraine and in the vasodilation and sensitization to pain typical of the pain phase.

Bromocriptine treatment of women with clomiphene-resistant polycystic ovary syndrome.

Twenty-three patients with polycystic ovary syndrome and anovulatory infertility have been treated with bromocriptine. All had previously failed to respond to clomiphene. Twenty had normal serum prolactin concentrations and, of these, four (20%) developed regular ovulatory cycles. All three women with moderate hyperprolactinaemia ovulated regularly on bromocriptine so that, overall, seven of 23(30%) responded, which was a significantly higher proportion than that observed during a control period of no treatment. A further eight women ovulated at least once during the study period but these occasional ovulations were no more common during bromocriptine than with either clomiphene or no treatment. No suppression of LH was noted except during the luteal phase of ovulatory cycles and there was no change in the pattern of pulsatile release of LH. Testosterone and androstenedione concentrations remained elevated and unchanged. We conclude that bromocriptine may be expected to induce ovulation in hyperprolactinaemic women with polycystic ovary syndrome but that there is no clear indication for its use in clomiphene-resistant patients with normal serum prolactin concentrations.

Prolactinemia during the menstrual cycle. A possible role for prolactin in the regulation of ovarian function.

We measured the concentration of circulating prolactin (PRL) in the serum during ovulatory and anovulatory cycles of normoprolactinemic menstruating women. The results demonstrate that during the luteal phase of ovulatory cycles a significant increase of PRL is observed together with that of progesterone. On the contrary, in menstruating women with anovulatory cycles we could not detect these increases. These data, analyzed together with the concomitant changes of gonadotrophins secretion, suggest a possible luteotrophic action of PRL in humans during the menstrual cycle.

Pulsatile gonadotropin secretion in women with hypothalamic amenorrhea: evidence that reduced frequency of gonadotropin-releasing hormone secretion is the mechanism of persistent anovulation.

Hypothalamic amenorrhea (HA) is a clinical disorder of unknown etiology. The diagnosis is made by exclusion of known abnormalities of pituitary and ovarian function. To determine if abnormalities of GnRH secretion could account for the anovulation and amenorrhea, we measured plasma gonadotropins every 20 min for 10- to 24-h periods in 19 women with HA. Ovarian steroids and gonadotropin responses to an iv bolus dose of GnRH (25 ng/kg) were also measured. The results were compared to those obtained during the early follicular (EF) and late luteal (LL) phases of ovulatory cycles in normal women. Plasma estradiol was lower (mean +/- SE, 52 +/- 5 pg/ml) than either cycle stage in normal women. Mean plasma LH was lower than EF values and FSH was higher than LL values. The amplitude of LH pulses in HA was similar to that in normal women. LH pulse frequency was the same as that present during the LL, but lower than that during the EF (HA, 4.7 pulses/12 h; EF, 7.7 pulses/12 h; P less than 0.05). In addition to the similar frequency, the patterns of LH secretion in HA resembled that of LL in that the amplitude of LH pulses was highly variable and pulses occurred at irregular intervals. Consistent changes in diurnal gonadotropin secretion were not found, and LH secretion was greater at night in 9 studies and during the day in 5 studies. Repeat studies in three patients (5-13 months later) revealed that LH pulse frequency was variable, being unchanged in 1, increased in 1, and decreased in the third patient. Thus, LH pulse frequency and, by inference, GnRH pulse frequency are similar in HA to those in the normal luteal phase despite a different steroid milieu. GnRH pulse frequency increases from the luteal to the follicular phases of normal cycles and may be important in the initiation of ovarian follicular maturation. These data suggest that the absence of cyclical gonadotropin secretion and anovulation in HA result from a decreased frequency and irregular amplitude of GnRH secretion and consequent absence of ovarian follicular maturation.

The role of androgens in adolescent cycles

Serum steroids and gonadotrophins were measured at days 6–9 and 20–23 of 209 adolescent cycles. Based on serum progesterone levels, about 80% of the cycles during the first gynecological year (years since menarche) were anovulatory, during the third, about 50%, and 6.0–7.5 years after menarche, 15% of the cycles were anovulatory. Testosterone was higher at days 6–9 and 20–23 in anovulatory cycles as compared with ovulatory ones. In addition, serum testosterone was higher in the latter part of the anovulatory cycles as compared to the beginning of the cycles. The pattern of serum androstenedione was very similar to that of testosterone. The only difference was that there were no significant differences between the ovulatory and anovulatory cycles in its concentration in samples taken at the beginning of the cycles. In the case of 5α-dihydrotestosterone, no significant differences were observed in its concentration between ovulatory and anovulatory cycles. However, its concentration was significantly higher in the luteal phase of ovulatory cycles as compared with the follicular phase. The midcycle increases in serum FSH and LH, seen in ovulatory cycles, occasionally appeared in anovulatory cycles, but were usually absent. The increase in serum LH in the latter part of the anovulatory cycles was converted to a decrease in ovulatory cycles. In addition, concentrations of FSH remained higher at the end of anovulatory cycles compared with the ovulatory ones. Animal experiments and evidence from clinical conditions associated with increased androgen production suggest that androgens have regulatory functions in the development of follicles. This evidence, put together with our present findings, suggests that the cyclic element in female reproduction is primarily ovarian in origin and is introduced by an androgen effect on maturing follicles. According to this concept, production of androgens by the first maturing follicles leads to a certain critical androgen concentration, resulting in follicular arrest and decreased steroid production. Repetitions of this process finally lead to synchronization of the endocrine feed-back processes operative during the reproductive life of woman.

Serum estradiol in women ingesting combination oral contraceptive steroids

The effect of combination oral steroid contraceptives upon serum estradiol levels was studied in 3 groups of women. Daily blood samples were obtained from 3 women for one control and 2 treatment cycles. Follicle-stimulating hormone, luteinizing hormone, and progesterone were also measured in these samples. In addition, estradiol levels alone were obtained daily and randomly in women who had been receiving long-term hormonal contraceptive therapy. In nearly all women receiving steroid contraceptives, endogenous estradiol levels were low, usually in the 20 to 80 pg. per milliliter range, similar to levels found in the early follicular phase of ovulatory cycles and greater than levels in postmenopausal women. The exogenous estrogen component of the hormonal contraceptives together with this level of endogenous estradiol production should be sufficient to prevent any deleterious effects associated with estrogen deficiency. The finding that estradiol levels remain low in the first cycle of therapy is consistent with previous studies which indicate that one of the mechanisms of action of hormonal contraceptives is a direct effect upon the ovary.

EEG Abnormalities Found in Healthy Women under Contraceptive Medication. I. Short Term Studies

In a previous study EEG abnormalities were detected in 2 of 24 healthy women during the 1st 3 months of treatment with various ovulatory and anovulatory contraceptive regimens. The present study is a follow up of the same group of women to detect possible EEG abnormalities occurring at the 6th and 12th months of treatment and those occurring within the 1st month after discontinuation of contraception. Only 17 women were studied (the 7 others were excluded due to voluntary treatment termination and pregnancy); they were divided into groups: 1) coil (5 cases) 2) microdoses (5 cases) and 3) sequential (4 cases) and combined (3 cases). In each case 3 consecutive pairs of routine EEG recordings (during the 6th and 12th months of contraceptive treatment and within 1st month of contraceptive discontinuation) and an equal number of plasma samples for progesterone/17 beta estradiol determination were taken. EEG routine recordings were also practiced during menstruation and during sleep. Procedures for routine EEG recordings and interpretation hormone determination standardization of dates and statistical significance of changes along the menstrual cycle were done as in the previous study. 4 of 7 patients in group 3 (the anovulatory sequential and combined contraceptive regimen) exhibited subclinical pseudoparoxysmal EEG discharges at the 6th and 12th months of treatment. These abnormalities may be due to the effect of specific hormone content of these particular compounds as they were not seen in control records taken before and after treatment and were seen on dates corresponding to the secretory phase of ovulatory cycles and concomitant to hormonal changes reflecting ovarian inhibition. In the coil group no abnormal EEG signs were observed in patients before during and after the regimen. 1 patient in the microdose group was found to have EEG abnormalities but the abnormalities were not attributed to the hormone content of the compound as abnormal EEG signs were found before and after treatment and were not concomitant to ovarian inhibition. No EEG abnormalities were observed in records taken during menstruation and during sleep of all the subjects.

Human thyroid-ovarian relationships: I. Influence of serum from various phases of ovarian cycle on goitrogenesis

1.1. Pooled serum from healthy adult males has no significant effect upon goitrogenesis in the rat.2.2. Pooled serum from the luteal phase of the menstrual cycle enhances goitrogenesis significantly; in contrast, pooled serum from the follicular phase shows some tendency to inhibit goitrogenesis, although this is not statistically significant.3.3. Menstrual and late luteal serum pools show effects upon goitrogenesis which support the concept of a thyroid cycle consonant with the ovarian cycle. The thyroid cycle appears to reach its height of activity during the premenstrual phase of the ovarian cycle and returns to its lowest level during the follicular phase.4.4. These constructs are in keeping with clinical observations of the normal male and with sequential observation of the normal female during the various phases of the ovarian cycle.

REPRESSION AND RESORPTION OF THE CORPORA LUTEA OF EARLY PREGNANCY FOLLOWING INJECTIONS OF TESTOSTERONE PROPIONATE¹²

IN RECENT experiments concerning the influence of testosterone propionate on transport of tubal ova in mice (i), it was observed that the corpora lutea were definitely repressed and eventually resorbed. The rate of deteriora' tion depended upon the amount of androgen injected daily and the total number of such injections. Mated animals were used and the first subcutaneous injections were given 10 to 14 hours after finding the vaginal plug (a.v.p.) since it was thought that early injections might interfere with the fertilization of ova. The use of mated animals is a decided advantage since this physiological phase of the ovarian cycle gives the experiment a definite starting point. This is particularly true if ova are found in the oviduct or uterus in those mice having indistinct corpora lutea. Two groups of animals are reported here, one of which received 5 mg. testosterone propionate daily, while