Perfil de FSH e LH na divergência folicular em novilhas Nelore (Bos indicus) / FSH and LH profiles during follicle deviation in Nelore heifers (Bos indicus)

O presente estudo teve como objetivo traçar o perfil de gonadotrofinas em 12 novilhas Nelore, a fim de testar a hipótese de que há declínio nas concentrações de FSH e elevação transitória nos níveis de LH durante a seleção folicular. A partir da ovulação (D0) foram colhidas amostras de sangue da veia jugular a cada 12 horas até o D5, para a dosagem de FSH e LH plasmáticos. Empregou-se o método de radioimunoensaio de duplo anticorpo. A sensibilidade do ensaio de LH foi de 0,02ng/ml e a de FSH de 0,005ng/ml. Os coeficientes de variação intra-ensaio foram 13,6% e 18,8%, respectivamente. Os dados (média±EPM) foram normalizados para o momento da divergência folicular e, posteriormente, analisados por ANOVA e por regressão inear, cúbica e quadrática. Também foi empregado o Teste t para comparação entre o ponto mais alto e o mais baixo da curva. Não se verificou efeito de tempo sobre as concentrações plasmáticas de FSH e de LH quando se utilizou análise de variância e de regressão. Entretanto, através do Teste t pontual, o FSH atingiu as menores concentrações plasmáticas 36 (0,40±0,05ng/ml) e 60 horas (0,42±0,04ng/ml) após a divergência, comparativamente às 36 horas anteriores ao desvio, quando as concentrações foram máximas (0,63±0,08ng/ml). Conclui-se, portanto, que há declínio nas concentrações plasmáticas de FSH, contudo, não foi comprovada elevação transitória nas concentrações de LH próximo ao momento do desvio folicular em fêmeas Nelore.

Present study aimed to evaluate gonadotropins profiles in 12 Nelore heifers, in order to test the hypothesis that FSH concentrations decrease and LH presents a transient increase during follicle selection. Blood samples from jugular vein were harvested twice daily starting at the time of ovulation (D0) until D5. Plasma samples were assayed for FSH and LH by double antibody radioimmunoassay method. LH and FSH assay sensitivity was 0,02ng/ml and 0,005ng/ml, respectively. The intraassay coefficient of variation was 13,6% and 18,8%, respectively. Data (mean±SEM) were normalized to follicle deviation and analyzed by ANOVA and by linear, cubic, and quadratic regressions. Comparisons between higher and lower FSH values were also performed by T-test. There was no effect of time in plasmatic FSH and LH circulating levels when variance analysis or regression analysis were performed. However, by T-test, FSH concentrations reached the lowest plasmatic levels 36 (0,40±0,05ng/ml) and 60 hours (0,42±0,04ng/ml) after follicular deviation, comparatively to 36 hours before deviation, when the concentrations were maximal (0,63±0,08ng/ml). In conclusion, there is a FSH decrease, although a transient LH elevation has not been confirmed encompassing follicle deviation in Nelore females.

Fertility impairment after mifepristone treatment to rats at proestrus. Actions on the hypothalamic-hypophyseal-ovarian axis.

Accumulated evidence indicates that the antigestagen mifepristone affects the reproductive axis acting on hypothalamic, pituitary, ovarian, and uterine tissues. The purpose of this study was to further investigate which reproductive functions are impaired by the antagonist, critically compromising the reproductive process, leading to unsuccessful pregnancy. Circulating pituitary and ovarian hormones, sexual receptivity, ovulation, and implantation rates were studied in cycling rats receiving a single dose of mifepristone (1 or 10 mg/kg subcutaneously) at 12:00 proestrus, before luteinizing hormone (LH) stimulation of the ovulatory process. Mifepristone-treated rats had decreased preovulatory surges of LH and prolactin (PRL), and hypersecretion of LH, PRL, and progesterone at estrus. The sexual receptivity was dramatically affected by the antagonist as indicated by the profound decrease in the lordosis response evaluated on the night of proestrus. The number of ovulating animals and the number of oocytes recovered from the oviduct on the morning of estrus were not affected by mifepristone. The low number of rats that succeeded in mating with potent males became pregnant. However, they delivered an average of only two pups at parturition, indicating a failure in the implantation of the fertilized ova, as ovulation was not affected by the antagonist at the dose used. We conclude that a dramatic inhibition of the sexual receptivity and unsuccessful implantation, preceded by a reduction on LH and PRL secretion, are the major components leading to fertility impairment after a single dose of mifepristone administered before the preovulatory surge of LH.

PIP: Mifepristone has been demonstrated to act on hypothalamic, pituitary, ovarian, and uterine tissue. To further investigate impairments in reproductive function triggered by this antagonist, circulating pituitary and ovarian hormones, sexual receptivity, ovulation, and implantation rates were studied in cycling Wistar rats receiving a single dose (1 or 10 mg/kg subcutaneously) of mifepristone at 12:00 proestrus, before luteinizing hormone (LH) stimulation of the ovulatory process. Treated rats had decreased preovulatory LH and prolactin (PRL) surges and hypersecretion of LH, PRL, and progesterone as estrus. A profound decrease in the lordosis response on the night of proestrus indicated a dramatic effect on sexual receptivity. There was no affect on the number of ovulating animals and the number of oocytes recovered from the oviduct on the morning of estrus. The few rats who succeeded in mating with potent males became pregnant, but they delivered an average of only two pups, indicating a failure in the implantation of the fertilized ova. These findings suggest that the dramatic inhibition of sexual receptivity and unsuccessful implantation, preceded by a reduction in LH and PRL secretion, are the major factors producing fertility impairment after a single dose of mifepristone before the preovulatory LH surge. factors such as smoking and parity.

Ultrasonographic and endocrine evaluation of ovarian function among Norplant implants users with regular menses.

With the objective of evaluating the ovulatory function among long-term Norplant implants users with regular menstrual cycles, we undertook this prospective study including 11 Norplant implants users and 11 control women who were not using hormonal methods of fertility control. Exposed and unexposed women had had at least three regular menstrual cycles preceding enrollment. All women were followed during one menstrual cycle by serial vaginal ultrasound and estradiol (E2), progesterone (P), LH, and FSH measurements. Three Norplant implants users ovulated, three had luteinization of an unruptured follicle (LUF), three had persistent follicle growth up to a mean of 33 mm without rupture, and two had no follicular development beyond 16 mm. Ten of the controls had normal ovulation and one had LUF. Mean peak LH and FSH among Norplant implants users who ovulated were three- to four-fold lower than among controls. Although users of Norplant implants with regular cycles frequently have luteal activity, the results of this study suggest that elevation of P during the second half of the cycle does not necessarily indicate ovulation has occurred and may frequently be associated with the presence of luteinized unruptured follicle. When ovulation occurs, there are usually abnormal hormone levels (low LH/FSH peak, low progesterone) which may also contribute to the contraceptive effect of Norplant implants.

Temporal relationship between Uniplant insertion and changes in cervical mucus.

This study was undertaken to determine the time required by a single implant containing nomegestrol acetate to affect cervical mucus production and sperm penetration in women. All subjects were investigated and, if necessary, treated for any kind of cervicitis or vaginitis prior to starting cervical mucus study. The subjects had not used hormonal contraception for at least three months prior to investigation. They were counseled to use condoms during this study and also to refrain from intercourse during the period of cervical mucus sampling. Follicular development and endometrial thickness were analyzed by transvaginal sonography. Cervical mucus examination, sperm penetration test, and transvaginal sonography were performed during the control cycle and during the first cycle of Uniplant use. Blood samples were taken for the measurement of estradiol, LH, and progesterone. Cervical mucus and sperm penetration tests were evaluated according to the World Health Organization (WHO) criteria. In the treated cycle, when cervical mucus reached a score of 8-10, Uniplant was inserted, independent of the day of the cycle. Cervical mucus was then collected at 0, 4, 8, 12, 24, 48, and 96 h later until a marked change in volume, consistency, ferning spinnbarkheit, and cellularity was observed. All samples were also used for sperm penetration test. Preovulatory estradiol and LH peak decreased significantly compared to pre-implant insertion. Progesterone levels were within the normal limit. Cervical mucus and sperm penetration tests were not affected by Uniplant in the first 12 h. Twenty-four hours after Uniplant insertion, cervical mucus and sperm penetration tests were affected in 70.6% of the women. Forty-eight hours after implant insertion, the women were affected. Follicular rupture occurred in the majority of the women 48 h after implant insertion. Based on these results, it is possible to conclude that Uniplant can affect estradiol and LH preovulatory peaks and disrupt the process of cervical mucus production and sperm penetration, but it was unable to prevent ovulation when inserted in the preovulatory phase.

PIP: In Brazil, physicians inserted one single capsule of the nomegestrol acetate contraceptive implant (Uniplant) subcutaneously in the gluteal region of 17 healthy female volunteers (mean age = 24.62 years) when their cervical mucus score was 8-10. They performed cervical mucus examination, sperm penetration test, and transvaginal sonography during the control cycle and during the first cycle of Uniplant use. They took blood samples to measure estradiol, luteinizing hormone (LH), and progesterone. Uniplant contained 55 mg of nomegestrol acetate. The researchers aimed to determine the time between Uniplant insertion and changes in cervical mucus and in the ability of sperm to exhibit forward motility in the cervical mucus. When Uniplant was inserted in the early follicular phase, the preovulatory peaks of estradiol and LH were significantly lower than preinsertion peaks (539.4 vs. 1087.1 pmol/l and 12 vs. 40.4 IU/l, respectively; p 0.01). The lower progesterone levels in the treatment cycle were not significantly different than preinsertion progesterone levels (46.6 vs. 53.8 nmol/l; p = 0.055). Ultrasonography and progesterone levels indicated that 16 of the 17 treatment cycles were ovulatory. Neither cervical mucus nor sperm penetration was affected in the first 12 hours postinsertion. By 24 hours postinsertion, 70.6% of the women exhibited significant changes in both cervical mucus and sperm penetration. At the end of 48 hours, all 17 women had these changes. These findings suggest that Uniplant inserted in the periovulatory phase affects cervical mucus production, sperm penetration, and preovulatory peaks of LH and estradiol but does not affect ovulation.

Effect of preovulatory insertion of Norplant implants over luteinizing hormone secretion and follicular development.

OBJECTIVE: To determine whether the process of ovulation could be interrupted by the insertion of Norplant implants (Leiras Pharmaceuticals, Turku, Finland) in the advanced preovulatory phase. DESIGN: Prospective study. SETTING: The Department of Biomedical Research at the Family Planning Clinic of PROFAMILIA, Santo Domingo, Dominican Republic. PATIENTS: Healthy women of reproductive age, requesting Norplant implants contraception. Thirteen of 15 women volunteers who were admitted completed the study. INTERVENTIONS: Norplant implants were inserted when the dominant follicle reached a mean diameter of 16 mm, based on serial vaginal ultrasounds (US) beginning on day 10 of the cycle. Blood samples for determination of E2, P, LH, and levonorgestrel, were taken and vaginal US performed at 0, 4, 24, 48, and 72 hours after insertion. If follicle rupture had not occurred at 72 hours after insertion, blood sampling and US were done three times per week during 2 additional weeks. RESULTS: Follicle rupture occurred in 11 of 13 subjects within 72 hours after insertion, with the exception of 1 subject in whom rupture occurred between 72 and 192 hours. Two women already had an LH peak at the time of insertion. In 9 of the remaining 11 women, a shortlasting, blunted LH surge was observed at 4 hours postinsertion. In the remaining two women, who had the lowest E2 levels, ovulation was inhibited, and a persistent follicle developed without luteinization. CONCLUSIONS: The insertion of Norplant implants in the advanced follicular phase will not inhibit ovulation if sufficient E2 priming has occurred. On the contrary, the exogenous progestin may rapidly foster ovulation shortly after.

PIP: 15 healthy women of reproductive age requesting Norplant were admitted into this prospective study conducted to determine whether the ovulation process can be interrupted by the insertion of Norplant implants during the advanced preovulatory phase. The implants were inserted when the dominant follicle reached a mean diameter of 16 mm, based upon serial vaginal ultrasounds (US) beginning day 10 into the cycle. Blood samples to determine levels of E(2), P, LH, and levonorgestrel were taken and vaginal US performed at 0, 4, 24, 48, and 72 hours after insertion. If follicle rupture had not occurred by 72 hours after insertion, blood sampling and US were done three times per week for two additional weeks. Follicle rupture occurred in 11 of the 13 subjects who completed the study within 72 hours after insertion, except for one subject who experienced rupture at 72-192 hours. Overall, it was determined that the insertion of Norplant implants during the advanced follicular phase will not inhibit ovulation if sufficient E(2) priming has occurred. The exogenous progestin, however, may rapidly foster ovulation shortly thereafter.

Effects of a single contraceptive Silastic implant containing nomegestrol acetate on ovarian function and cervical mucus production during 2 years.

OBJECTIVE: To study the mechanism of action of Uniplant (South to South Corporation in Reproductive Health, Salvador, Brazil), a single Silastic capsule containing nomegestrol acetate (Lutenyl, Theramex, France) in women during 2 years. DESIGN: Comparison between the hormonal levels, follicular development, cervical mucus (CM) production, and endometrial thickness in the menstrual cycle before implant insertion and at 1, 6, 12, 18, and 24 months after implant insertion. PARTICIPANTS: A total of 15 women of reproductive age were enrolled for the 1st year of use. Twelve of these women continued for a 2nd year of Uniplant use. MAIN OUTCOME MEASURES: Hormonal plasma levels were measured in control cycles and at 1, 6, 12, 18, and 24 months of Uniplant use. Cervical mucus, follicular development, and endometrial thickness also were evaluated. RESULTS: In this study, Uniplant blocks ovulation in 86 percent of cycles studied. Disturbances in follicular growth were observed also. Cervical mucus was scanty and viscous in all women during this study. Endometrial thickness was <8 mm in all cycles studied. CONCLUSION: This study shows that Uniplant is a long-acting contraceptive that probably acts at the hypothalamic-pituitary levels, on the ovary, on CM production, and on the endometrium. These properties suggest the use of Uniplant as a contraceptive agent, especially if one considers the lack of androgenic and metabolic effects and the maintenance of periodic bleeding similar to menstruation.

PIP: A total of 15 healthy women volunteers were enrolled in this study. Their mean age was 23 +or- 1.2 years (range, 18-33 years), mean weight was 55.7 +or- 2.6 kg (range, 40-72 kg), and mean parity was 1.1 (range, 0-4). Venous blood samples were drawn every other day from day eight of the cycle until sonographic evidence of a 12-mm follicle, and then every day until sonographic evidence of follicular rupture and thereafter every other day until the next menstrual bleeding. The capsules were removed at the end of one year of Uniplant use, and a new capsule was inserted in 12 subjects. The blood samples for hormonal analyses were taken after 18 and 24 months of Uniplant use in the 12 women who continued in the study. Levels of luteinizing hormone (LH) were significantly lower than in the control cycles during the observation period (p .01, p .05). According to transvaginal sonography, four different patterns of follicular development were found: normal follicular growth and rupture, persistent follicle, follicular cysts, and no follicular growth. Follicular growth and rupture were observed in 20% of the treated cycles. Persistent follicles were present in approximately 15% of the treated cycles. Follicular cysts were observed in 29% of the cycles studied during 24 months of Uniplant use. All subjects had normal cervical cytology before starting treatment, after 12 months, and after 24 months of Uniplant use. The maximum cervical mucus score for pretreatment cycles was 12.8 +or- 0.4. Endometrial thickness was 8 mm in all cycles studied. 58% (7 of 12) of the women showed a normal menstrual cycle (26 to 32 days). 33% (4 of 12) of the women experienced one or two episodes of amenorrhea (90-134 days), whereas 8.3% of women (1 of 12) experienced episodes of spotting, six times in a period of 24 months of Uniplant use (10-30 days). Before Uniplant insertion, plasma concentration of sex hormone binding globulin was 72.3 nmol/L. After 24 months of Uniplant use, the concentration was 78.0 nmol/L.

A comparative study on the return to ovulation following chronic use of once-a-month injectable contraceptives.

A comparative study was undertaken involving 21 Mexican women who discontinued the use of medroxyprogesterone acetate 25 mg plus oestradiol cypionate 5 mg (Cyclofem) and norethisterone enanthate 50 mg plus oestradiol valerate 5 mg (Mesigyna) to assess the time required for the return to menses and ovulation. All subjects were exposed to once-a-month injectable contraceptives for two years and were followed for 120 days after the last injection. The urinary concentration of oestrone glucuronide and pregnanediol glucuronide was determined daily in all subjects beginning one month after the last injection. The results disclosed that ovulatory cycles were documented after 120 days of the last injection in six women of each studied group. Similar endometrial bleeding patterns were observed in both groups, indicating that the two drugs have alike pharmacokinetic and pharmacodynamic effects.

PIP: At the family planning clinic of the medical school in Coahuila, Mexico, providers recruited 11 volunteers requesting an injectable contraceptive into Group I (Mesigyna: 50 mg norethisterone enanthate + 5 mg estradiol valerate) and 10 similar volunteers into Group II (Cyclofem: 25 mg medroxyprogesterone acetate + 25 mg estradiol cypionate). After they used the injectables continuously for two years, researchers followed them for 120 days after the last injection. Early morning urine samples were taken every day between day 30 and day 120 after the last injection to measure estrone glucuronide and pregnanediol glucuronide. Researchers also measured the urinary luteinizing hormone level. Normal ovulatory cycles returned within the first to third month after injection in six users from each group. In fact, all but one woman in the Group I had a normal ovulatory cycle during the first month. The other woman had a normal cycle during the second month. During months 1, 2, and 3, the numbers of women in group II who had a normal ovulatory cycle were 3, 2, and 1, respectively. The two groups did not have significant differences in the first bleeding-free interval (51 for Group I vs. 43 for Group II) and in the total number of bleeding/spotting days (11 vs. 14). These findings suggest that long-term use of these injectable contraceptives did not cause chronic inhibition of the hypothalamus-pituitary-ovarian axis and that the ovarian function and the endometrial bleeding patterns returned to normal similarly in both groups. Thus, national family planning programs in developing and developed countries may want to consider offering them as part of the contraceptive mix.

Lactation, nutrition and fertility and the secretion of prolactin and gonadotrophins in Mopan Mayan women.

The effect of lactation on menstrual cycles, ovulation and conception was studied in a group of non-contracepting Amerindian Mopan Mayan women. Anthropological observations of relevant events were made over a 21-month period. Blood samples were assayed to determine the plasma concentrations of prolactin, luteinising hormone, follicle stimulating hormone, human chorionic gonadotrophin, placental lactogen, oestrogen, progesterone and cortisol. The data show that: frequent and prolonged breast-feeding was associated with a marked increase in plasma prolactin concentrations to levels similar to those in lactating Gaing but higher than those in lactating Scottish women; ovulatory menstrual cycles and pregnancy occurred during frequent lactation; in lactating menstruating women there was an inverse correlation between fat weight and months post-partum. These data suggest that other factors as well as suckling account for the effects of lactation on fecundity.

PIP: Lactation, ovulation and conception were observed as part of an anthropological study of Amerindian Mopan Mayan women from the village of San Jose Hawaii in western Belize from March 1985-January 1987. Single blood samples from each subject were immunoassayed for prolactin, LH, FSH, hCG, placental lactogen, estrogen, progesterone and cortisol. Anthropomorphic data analyzed were body mass index (BMI), fat/weight percentage, total body water and lean body weight. 117 women had at least 1 child during the study; 91 were lactating; 51 reported no menstrual cycles. 50 submitted to blood testing. Almost all infants were breast fed for 18 months or longer, up to 3 years, typically at least 6 times per day and 3 times per night. Women averaged 9 live births and 8 surviving children, with a mean birth interval of 28 months. 25 of the 29 women known to be pregnant conceived while lactating. 16 lactating women were pregnant. Their culture requires them to have 3 menses before conception to nourish the fetus, yet forbids speaking about menstrual blood: women fabricated menstrual dates, but in confidence 51 of 81 stated that they did not menstruate before the last conception. Most often menses began 12 months postpartum. Lactating women had heightened prolactin levels even if supplementing their children's diet. Thus frequent lactation delayed onset of menses, but supplementation had no effect. Most of the women were within the normal range of BMI, but 13% were below normal. In lactating menstruating women there was a significant negative correlation between fat weight and postpartum month. The data suggest that the interval to conception or menstruation was inversely correlated with fat weight. Here suckling frequency rather than prolactin levels seems to postpone fertility. In this society, with 10-12 births and 9-10 children in the completed family, the largest in the world, prolonged frequent lactation has little effect on fertility. Instead, birth trauma, maternal mortality, fetal and infant mortality, and perhaps nutrition, have more effect on completed family size.

Ovulatory dysfunction during continuous administration of low-dose levonorgestrel by subdermal implants.

OBJECTIVE: To study the endocrinologic profile of regularly menstruating users of levonorgestrel subdermal implants. DESIGN: Observational, prospective, case-controlled comparative study. SETTING: The Family Planning Clinic of PROFAMILIA, in Santo Domingo, Dominican Republic. PATIENTS, PARTICIPANTS: Thirty one regularly cycling Norplant users and 12 nonhormonal contraceptors who volunteered to participate. INTERVENTIONS: Norplant contraceptive implants were inserted in 31 subjects between 13 and 77 months before this study. MAIN OUTCOME MEASURES: Follicle-stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were serially assayed for one menstrual cycle. RESULTS: Almost half of the cycles among Norplant users were anovulatory; all the rest (55%) had some form of dysfunction: diminished gonadotropin surge, luteal phase insufficiency (low P levels and shortened luteal phase), and E2 profiles different from normal controls. CONCLUSIONS: Anovulation is clearly one of the main mechanisms of action of Norplant, but even in presumptive ovulatory cycles, the dysfunctions described possibly contribute to the high contraceptive effectiveness of Norplant.

PIP: The study sought to examine the endocrinologic profile of regularly menstruating users of levonorgestrel subdermal implants. This observational, prospective, case-controlled, comparative study occurred at the Family Planning Clinic of PROFAMILIA in Santo Domingo, Dominican Republic. 31 subjects agreed to receive Norplant contraceptive implants between 13-77 months prior to this study and there were 12 nonhormonal contraceptors who also volunteered to participate. Follicle stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were serially assayed for 1 menstrual cycle, and almost 1/2 of the cycles of norplant acceptors were anovulatory: the remainder (55%) had some form of dysfunction such as diminished gonadotropin surge, luteal phase insufficiency (low P levels and shortened luteal phase), and E2 profiles different from controls. Anovulation is clearly 1 of the main mechanisms of Norplant action, but even in presumptive ovulatory cycles, the dysfunctions described could have contributed to the high contraceptive effectiveness of Norplant.

Variable effects of RU 486 on endometrial maintenance in the luteal phase extended by exogenous hCG.

This study was designed to assess the features and conditions for endometrial bleeding induction with the synthetic antiprogestin and antiglucocorticoid RU 486 during hCG-induced prolongation of the luteal phase. Eighteen healthy, surgically sterilized women and another five women with an intrauterine contraceptive device (IUD) participated. All subjects received hCG which was injected daily in increasing doses (500 to 15,000 IU) from day 9 to day 15 of the luteal phase. Ten subjects received hCG alone, and groups of three to 16 subjects received hCG combined with RU 486 (25, 50, 100, 200 or 400 mg/day). RU 486 administration was commenced on day 12 following the LH surge and given either for 1, 4 or 7 consecutive days. In certain cycles, tamoxifen (20 mg/day) was given for 4 consecutive days with hCG, or with hCG and RU 486. All treatment cycles were separated by one or two resting cycles. Frequent blood samples were taken to monitor the endocrine response. Treatment with hCG alone or with the various combinations of RU 486 produced similar serum levels of oestradiol and progesterone which were equivalent to those observed during early pregnancy. With hCG alone, the onset of bleeding was on day 21-24 after the LH surge, coinciding with the drop in oestradiol and progesterone. With RU 486 doses of 50 mg/day or more, an early bleeding episode almost invariably occurred on day 14-17 after the LH surge in the presence of high circulating steroid levels. In contrast, 25 mg/day RU 486 for 4 days failed to induce this early onset of bleeding in three out of six cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: When administered during the luteal phase of the menstrual period, human chorionic gonadotropin (hCG) has been observed to induce a pseudopregnancy in which the functional lifespan of the corpus luteum is prolonged. On the assumption that women with hCG-induced prolongation of the luteal phase offer an ideal model for studying the in vivo action of RU-486 and other antiprogestins, 23 women (5 of whom were IUD users) were administered hCG alone. hCG, and RU-486, tamoxifen, or both RU-486 and tamoxifen. Increasing doses of hCG produced a progressive rise in estradiol and progesterone to levels compatible with early pregnancy; steroid levels declined after cessation of hCG treatment and bleeding occurred 21-24 days after the midcycle luteinizing hormone (LH) surge. This indicates that the luteal phase was prolonged by at least 8 days. RU-486 doses of 50 mg/day and above produced bleeding 14-17 days after the LH surge in the presence of high levels of circulating steroids, while a 25 mg dose of RU-486 failed to produce bleeding in 50% of cases and tamoxifen failed to induce early bleeding or to potentiate the effect of RU-486 at either dose. A 2nd bleeding episode occurred 22-24 days after the LH surge coincident with a drop in circulating steroids in 43% of cycles; a 2nd bleeding episode was significantly correlated with a lower total dose (200 and 400 mg) of RU-486. Endometrial biopsies in those with late bleeding showed a mixed proliferative and secretory pattern indicative of incomplete shedding. A total dose of 700 or 800 mg of RU-486 is recommended to produce complete shedding.

Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin.

To assess the effect of hormonal monthly injectable contraceptives upon the serum values of immunoreactive prolactin (Prl), three groups of women of reproductive age exposed to different estrogen-progestogen injectable formulation for a minimum of one year were studied. The first group (n = 10) received dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg (DHPA/E2-EN), Group 2 (n = 21) received medroxyprogesterone acetate 25 mg and estradiol cypionate 5 mg (MPA/E2-C) and Group 3 (n = 19) was exposed to norethisterone enanthate 50 mg and estradiol valerate 5 mg (NET-EN/E2-V). A group of IUD users (n = 16) served as the control group. Serum Prl and 17 beta-estradiol (E2) concentration were determined in blood samples (0 and 15 min.) on days 0 (day of last injection), 10, 20 and 30 after last contraceptive injection. The results demonstrated a slight though not significant increase (p greater than 0.05) in serum Prl in the three experimental groups as compared with the IUD control group. This increase in Prl levels observed on day 10 post-last injection never exceeded the upper limits of the normal range (20 ng/ml). Overall, the data demonstrated that the chronic administration of these estrogen/progestogen once-a-month injectable contraceptives does not affect the Prl baseline secretion in women.

New insights on the mode of action of intrauterine contraceptive devices in women.

To gain a better understanding of the mechanism of action of intrauterine devices (IUDs), a search was made for ova in the genital tracts of 115 women using no contraception and of 56 women using IUDs, all of whom volunteered for study in conjunction with surgical sterilization. Ova were recovered from tubal flushings between 48 and 120 hours after the midcycle peak of luteinizing hormone in 39% of the IUD users compared with 56% of women in the control group (0.05 less than P less than 0.10). This suggests an action of the IUD before the ovum reaches the uterus. Eggs with a microscopic appearance consistent with fertilization were recovered from the fallopian tubes of half of the women using no contraception who had intercourse within the fertile period of the reproductive cycle and from whom ova were recovered. In contrast (P less than 0.01), no eggs with this appearance were recovered in IUD users who had intercourse within the fertile period. No ova were recovered from the body of the uterus of any of the IUD users. Fertilized ova are less likely to reach the uterine cavity containing an IUD. Thus, the principal mode of IUDs is by a method other than destruction of live embryos.

[Influence of combined oral contraceptives on prolactin blood levels (author's transl)].

PIP: The authors studied the effects of the use of combined pills on serum prolactin (PRL) levels. Serum PRL levels were determined by radioimmunoassay in 9 women using combined pills for at least 6 months. Each woman was sampled 6 times during the month of study. The authors conclude that combined pills increase PRL serum levels in a much higher proportion than the spontaneous incidence of hyperprolactinemia and suggest that this effect is strongly related to the length of pill use. (author's modified)^ieng

Effects of lactation on hormonal levels in rural women.

Luteinizing hormone, follicle-stimulating hormone and prolactin levels were compared in ten rural and ten urban women, all of whom were experiencing lactational amenorrhea. The values of luteinizing hormone and follicle-stimulating hormone were similar in both groups. The prolactin levels were significantly elevated in the rural group.

PIP: Luteininzing hormone (LH), follicle-stimulating hormone (FSH) and prolactin levels were compared in 10 rural and 10 urban women in Mexico who were experiencing lactational amenorrhea in an effort to define any differences for these 2 groups. All the women had breast fed their babies without supplementation, and none of the women had menstruated or had taken oral contraceptives. Another 20 women who attended the Clinic for Family Planning and who did not take OCs served as controls. All the women had an extended postpartum period that varied from 9-12 months. The levels of LH in the urban group fluctuated between 1.0 and 12.0 Imu-ml, with an average of 5.1 Imu-ml. The FSH levels among the urban group ranged from 3.0 to 15.0 with an average of 7.3 Imu-ml, while the average prolactin level was 20.4 ng-ml. Duration of lactation varied from 7 to 16 months for the rural women. Their LH and FSH levels were similar to those of the urban group, but their prolactin levels were more elevated than those found in the urban group. The average prolactin level was 38.1 mg.ml, and this elevation was statistically significant. The LH values among the 20 controls fluctuated between 3.0 and 20.0 Imu-ml, with an average of 9.2 ImU-ml. The FSH levels for the control group ranged from 3.4 to 17.0 ImU-ml, with an average of 8.1 ImU-ml. Prolactin levels varied between 10.1 and 17.0 ng-ml, with an average of 14.5 ng-ml.

[Hormonal tissue concentration and oral contraceptives: the endometrium]. / Concentración hormonal tisular y los anticonceptivos orales: el endometrio.

PIP: The study investigates hormonal control of the menstrual cycle, adrenal function role, and endouterine menstrual disorders by an analysis of peripheral hormones and of their concentration at endometrial level. The authors also present a new radioimmunoassay method for determining hormone presence in plasma and in the endometrium. 59 ovulatory cycles were considered, and ovarian hormones were found to be 10-20 times higher in tissue than in plasma, but not in women under sequential or combined oral contraceptive treatment. The relation between endometrial estrogens and progesterone with plasma follicle stimulating hormone and luteinizing hormone levels is discussed, together with the significance of tissue hormone concentration.^ieng

[Effect of chlormandinone acetate upon seizures in epileptic children with latent signs of hyperandrogenism]. / Efecto del acetato de clormadinona sobre las crisis convulsivas en niños epilèpticos con signos sugestivos de hiperandrogenismo

The effect of chlormadinone acetate (24 mg/day) upon the plasma levels of pituitary gonadotropins and gonadal hormones on the number of generalized convulsions and spike EEG density was investigated in a group of epileptic children with intractable seizures and with clinical signs suggestive of hyperandrogenism. In each case, the effect of chlormadinone was evaluated in relation to hormonal levels and seizures observed during a control period and under the effect of placebo as follows: Control (PC)-Chlormadinone acetate (PCL1)-Placebo (PP)-Chlormadinone acetate (PCL2). In a male child (4MS), the number of convulsive attacks observed in the control period (26/month) was reduced during PCL1 (2/month) increased during PP (12/month) and was reduced again during PCL2 (0/month). Spike EEG density showed a parallel course to the clinical attacks. In this case, control levels of testosterone were markedly elevated (40 ng/ml) and were decreased during PCL1 to 4.0 increased again during PP to 34.0 and decreased again during PCL2 to 1.2 ng/ml. Plasma levels of pituitary gonadotropins were unchanged throughout the entire period of study. In other cases, neither the number of epileptic attacks nor spike EEG density were apparently affected by this regime and plasma levels of pituitary gonadotropins and gonadal hormones were also unmodified. These results suggest that a latent state of hyperandrogenism may be detected in some epileptic patients with intractable seizures and that chlormadinone may reduce convulsive attacks in these patients, probably by decreasing testosterone plasma levels.

PIP: The effect of chlormadinone acetate (24 mg/day) upon the plasma levels of pituitary gonadotropins and gonadal hormones on the number of generalized convulsions and spike EEG density was studied in a group of epileptic children with intractable seizures and with clinical signs suggestive of hyperandrogenism. In each case, the effect of chlormadino ne was evaluated in relation to hormone levels and seizures observed during a control period and under the effect of placebo, as follows: Control (PC); Chlormadinone acetate (PCL1); Placebo (PP); Chlormadinone acetate (PCL2). In a male child, the number of convulsive attacks observed in the control period (26/month) was reduced during PCL1 (2/month), increased during PP (12/month) and reduced again during PCL2 (0/month). Spike EEG density showed a parallel course to the clinical attacks. In this case, control testosterone levels were markedly high (40 ng/ml) and decreased during PCL1 to 4.0, increased again during PP to 34.0 and decreased again during PCL2 to 1.2 ng/ml. Plasma levels of pituitary gonadotropins were unchanged during the entire period of study. In other cases, neither the number of epileptic attacks nor spik e EEG density were apparently affected by this treatment and plasma levels of pituitary gonadotropins and gonadal hormones were also unchanged. These findings suggest that a latent state of hyperandrogenism may be detected in some epileptic patients with intractable seizures and that chlormadinone may reduce convulsive attacks in these patients, probably by decreasing plasma testosterone levels.

Proceedings: Interaction between gonadal steroids and LH-releasing hormone to control gonadotropin secretion at the pituitary level.

PIP: Previously, it was shown that intact or castrated female rats which were pretreated with estradiol for 48-72 hours had an increased sensitivity to exogenous LH-Releasing Hormone (LRF). The findings indicated a biphasic effect of estrogen on the pituitary responsiveness to LRH, probably dependent upon the time of exposure of the pituitary to the steroid. A series of experiments were performed in which pituitary sensitivity to LRF was tested at various times after estradiol treatment in ovariectomized mice. Sensitivity to LRF was significantly decreased 3 hours after estradiol treatment. No difference in anterior pituitary sensitivity to LRF was found between control and experimental groups in 6 hours. 9 hours after treatment, there was a clear increase in response; and in animals treated for 24 hours, there was an even higher response. It has been suggested that progesterone may also alter pituitary sensitivity to LRF, but this was not shown to be true in ovariectomized rats. The biphasic effect of estradiol on pituitary sensitivity to LRF suggests that the changes in sensitivity may play a role during the normal estrous cycle. The time of exposure of the anterior pituitary to estradiol rather than the dose is the important factor in determining the inhibitory or facilitatory response to LRF.^ieng

[Medical induction of ovulation. Study on 250 cases]. / Inducción médica de la ovulación. Estudio sobre 250 casos

PIP: The results obtained in 250 patients treated with preparations that induce ovulation are reported. 212 were treated with clomiphene citrate, obtaining ovulation in 86.3% of the cases and 32.2% pregnancies; 12 of the 68 pregnancies ended in abortion; 2 (2.9%) produced twins; all the babies delivered were normal. Success depends on the cause of the prior absence of ovulation, and specifically on the estrogen level, with very good results with high estrogen level and very poor results when it is low. The drug is very well tolerated, with slight side effects in only 10% of the cases and without need for special treatment. 27 patients were treated with gonadotropins from menopausal women (Pergonal), with ovulation in 74.1% and pregnancy in 29.6% of the cases; 2 out of 8 pregnancies were multiple (with 2 and 3 products). 11 cases were treated with corticoids, obtaining 72.7% ovulation and 27.3% pregnancy rates. The luteinizing hormone (LH) curve should be determined in order to select the proper treatment; cases with a normal LH curve should be treated with clomiphene; gonadotropins should be used when LH is absent; neither treatment is appropriate when LH is normal without ovarian response; corticoids are indicated in case of excessive excretion of male hormones.^ieng