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Biomedical subjects

H M Fraser

Publications and source records attributed to H M Fraser.

At least 19 recordsLinked to original sources
PubMed1992

Long-acting gonadotrophin releasing hormone agonist implant causes variable duration of suppression of ovarian steroid and inhibin secretion.

OBJECTIVE: The duration of action of a gonadotrophin releasing hormone (GnRH) agonist implant designed to be effective for 3 months was investigated in women by monitoring drug release and ovarian hormone secretion. Serum inhibin secretion was measured to determine whether the secondary rise in serum FSH concentrations observed during long-term GnRH agonist treatment was attributable to changes in inhibin secretion. DESIGN AND PATIENTS: The implants of slowly biodegradable polylactide/glycolide (molar ratio 75:25) containing 3.3 mg buserelin, D-Ser (But)6-GnRH (1-9)-nonapeptide-ethylamide, in a rod 1 cm long and 0.13 cm diameter were injected s.c. in patients with endometriosis (3.3 mg buserelin in four patients, 6.6 mg buserelin in six patients). MEASUREMENTS: Urinary secretion of oestrone, pregnanediol, LH and buserelin were determined in daily samples collected for 2 cycles before treatment, during treatment, and for 2 recovery cycles. Oestradiol, progesterone, inhibin, LH and FSH were measured in serum collected once per week. RESULTS: In all patients ovarian hormone secretion was suppressed successfully but considerable variability occurred in the length of time taken for ovarian function to recommence, time to return to ovulation being 100-194 days (median 118 days) (3.3 mg group) and 79-290 (median 178 days) (6.6 mg group). After implant injection, there was a rapid rise in the urinary buserelin excretion followed by an early fast phase of buserelin release, half life (t1/2) = 9 days for 3.3 mg implant and 11 days for 6.6 mg implant. This was followed by a second phase representing a plateau of release, t1/2 = 50 days (3.3 mg implant) and 90 days (6.6 mg implant). During this second phase, an excretion rate of greater than 0.2 nmol buserelin/mol Cr was associated with oestrone excretion at or below early follicular phase values. Once buserelin excretion fell below 0.1 nmol/mol Cr, ovarian function returned in all patients. The period for which buserelin secretion was maintained between 0.1 and 0.2 nmol/mol Cr corresponded to the time taken to recovery of ovulatory cycles in 8/10 of the women. In 9/10 patients serum immunoreactive inhibin concentrations declined at 2 weeks, along with the suppression of oestradiol, and remained suppressed throughout the period of anovulation. Recovery of FSH secretion began after 4-5 weeks. CONCLUSIONS: While this implant should have important clinical application where chronic treatment is indicated, further work is needed on design of long-term implants so that such preparations can be used when precise return to ovarian activity is required. A fall in inhibin secretion may contribute to the secondary rise in FSH by withdrawal of negative feedback but these events are not closely correlated.

Adult↗
PubMed1992

Suppression of pulsatile luteinizing hormone secretion by gonadotrophin-releasing hormone antagonist does not affect episodic progesterone secretion or corpus luteum function in ewes.

Progesterone secretion has been observed to be episodic in the late luteal phase of the oestrous cycle of ewes and is apparently independent of luteinizing hormone (LH). This study investigated the effects of suppressing the pulsatile release of LH in the early or late luteal phase on the episodic secretion of progesterone. Six Scottish Blackface ewes were treated i.m. with 1 mg kg-1 body weight of a potent gonadotrophin-releasing hormone (GnRH) antagonist on either day 4 or day 11 of the luteal phase. Six ewes received saline at each time and acted as controls. Serial blood samples were collected at 10 or 15 min intervals between 0 and 8 h, 24 and 32 h, and 48 and 56 h after GnRH antagonist treatment and daily from oestrus (day 0) of the treatment cycle for 22 days. Oestrous behaviour was determined using a vasectomized ram present throughout the experiment. Progesterone secretion was episodic in both the early and late luteal phase with a frequency of between 1.6 and 3.2 pulses in 8 h. The GnRH antagonist abolished the pulsatile secretion and suppressed the basal concentrations of LH for at least 3 days after treatment. This suppression of LH, in either the early or late luteal phase, did not affect the episodic release of progesterone. Daily concentrations of progesterone in plasma showed a minimal reduction on days 11 to 14 after GnRH antagonist treatment on day 4, although this was significant (P < 0.05) only on days 11 and 13. There was no effect of treatment on day 11 on daily progesterone concentration, and the timing of luteolysis and the duration of corpus luteum function was unaffected by GnRH antagonist treatment on either day 4 or day 11. These results indicate that the episodic secretion of progesterone during the luteal phase of the oestrous cycle in ewes is independent of LH pulses and normal progesterone secretion by the corpus luteum can be maintained with minimal basal concentrations of LH.

Analysis of Variance↗
PubMed1992

Influence of the gonad on the degree of suppression induced by an LHRH agonist implant in the marmoset monkey.

In a previous study pituitary-testicular function was shown to be maintained in a New World primate after the administration of an LHRH agonist implant. In the present study the mechanism of action of the same LHRH agonist (buserelin) on pituitary-gonadal function in the marmoset was investigated and a comparison made between the effects of treatment in three intact males, six adult cyclic females with regular ovulatory cycles, and six long-term ovariectomized animals. These were injected s.c. with an LHRH agonist implant (1.5 mg buserelin in a rod 0.5 cm long). In both the males and intact females, basal plasma LH concentrations were maintained within the normal range throughout the expected duration of agonist action (at least 3 months). Despite this, an absence of response to an LHRH challenge indicated that pituitary desensitization had occurred. In the intact females, ovulation was inhibited in five of six animals, plasma progesterone concentrations initially being maintained but subsequently remaining suppressed until 136 +/- 18 (S.E.M.) days after treatment. Responsiveness to administered LHRH returned prior to onset of return to ovarian cycles. In contrast, in ovariectomized marmosets, plasma LH was markedly suppressed to concentrations which were at or below the limit of detection of the assay and were therefore less than those observed in the buserelin-implanted intact animals. These results show that apparently normal pituitary-gonadal function in this species disguises an underlying pituitary desensitization to LHRH. This allows continuation of testosterone secretion in the male, but in the female ovulation is prevented, presumably as a result of failure of the desensitized pituitary to produce an LH surge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Immunoneutralization and immunocytochemical localization of inhibin alpha subunit during the mid-luteal phase in the stump-tailed macaque.

The putative endocrine role of inhibin in the control of FSH secretion during the luteal phase in the primate was investigated by immunoneutralization. Antisera against the 1-23 amino acid sequence of the N-terminus of the human inhibin alpha subunit were raised in a ewe and three macaques. Antisera (10-20 ml) were administered to macaques on day 8/9 of the luteal phase and serum samples collected during the treatment cycle and post-treatment cycle for determination of FSH, oestradiol and progesterone. In addition, localization of inhibin within the macaque ovary at this stage of the luteal phase was investigated using the ovine antiserum. Intense immunostaining was localized within the granulosa-lutein cells of the corpus luteum with absence of staining in the theca-lutein cells or other ovarian compartments. Administration of antisera was without significant effect on serum concentrations of FSH when compared with control animals, either during the first 24 h of detailed observation or for the following 10-day period of the late luteal phase and subsequent early follicular phase. These results provide further evidence that the corpus luteum is the major source of inhibin immunoreactivity during the primate menstrual cycle, but fail to support an endocrine role for inhibin in the suppression of FSH secretion.

Animals↗
PubMed1991

Effect of late follicular phase administration of antide on ovulation and inhibin secretion in macaques.

In previous studies, the LHRH antagonist detirelix, administered to stumptailed macaques during the menstrual cycle, was only partially effective in blocking pituitary-ovarian function when given during the late follicular phase. Since the antagonist was suppressive when administered during the early luteal phase, we investigated the ability of antide, a putative long-acting LHRH antagonist, to cause inhibition of the LH surge or luteal function when administered during the late follicular phase. Six animals with regular ovulatory cycles were treated on day 10 of the follicular phase with 1mg/kg antide s.c. All animals demonstrated a continued rise in serum concentrations of estradiol which were followed by an LH surge beginning 2-5 days after antide injection and serum progesterone and inhibin secretion which indicated normal luteal function. In a second experiment, six animals were treated on day 10 of the follicular phase with 3mg/kg antide s.c. In three animals, this caused a fall in serum concentrations of estradiol and the expected LH surge and rises in progesterone and inhibin secretion indicating ovulation failed to occur. In 2 animals, the LH surge was not prevented but the consequential rise in progesterone and inhibin was attenuated. In the remaining animal the cycle appeared unaffected. Pharmacokinetics of antide revealed an initial high release rate during the first 4 days (1mg/kg) or 6 days (3mg/kg) followed by a period of sustained release at a relatively low level. These results show that antide is partially effective in blocking ovulation at a high dose in the macaque and may result in an inadequate luteal phase, presumably as a result of its extended action.

Animals↗
PubMed1991

Control of progesterone and inhibin secretion during the luteal phase in the macaque.

We investigated the temporal relationship between serum concentrations of progesterone and immunoreactive inhibin after treatment with an LHRH antagonist ([N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10++ +] -LHRH), during the mid-luteal phase in the macaque. Further, in an attempt to obtain a model of transitory suppression of luteal function, the effect of treatment with the LHRH antagonist for 1, 2 or 3 days during the mid-luteal phase on serum concentrations of progesterone and immunoreactive inhibin was compared. Differences in the pattern of decline of the two hormones were observed. Progesterone concentrations fell by 6 h after antagonist administration while inhibin was not significantly suppressed until 48 h. Treatment with three injections of LHRH antagonist caused a sustained suppression of luteal function as shown by low serum concentrations of progesterone and inhibin. Recovery of progesterone and inhibin secretion was observed in two out of six macaques treated with two injections of antagonist and in three out of six treated with a single injection. Therefore, with the regimens of LHRH antagonist which we employed this approach was not conducive to obtaining a reliable transitory suppression of luteal function. To elucidate further the gonadotrophin control of inhibin, six macaques were treated with three injections of the LHRH antagonist to induce a permanent suppression of luteal function but received concomitantly either human chorionic gonadotrophin (hCG) or human FSH daily for 5 days (n = 3 per group). FSH failed to prevent the antagonist-induced fall in progesterone and inhibin while hCG treatment completely reversed the inhibitory effects of the LHRH antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Immunocytochemical localization of inhibin alpha-subunit in the human corpus luteum.

The localization of inhibin alpha-subunit within the human corpus luteum was investigated. The antiserum used was raised in sheep against the first 1-23 amino acid sequence of the N-terminus of the human inhibin alpha-subunit. Using the avidin-biotin immunoperoxidase technique, intense immunostaining was localized within the granulosa-lutein cells of the corpus luteum, with absence of staining in the theca-lutein cells and surrounding ovarian tissue. Similar distribution of inhibin alpha-subunit immunostaining was observed in 12 corpora lutea obtained during the early, mid- and late-luteal phases and no changes in intensity were apparent at these different stages. Negative controls were obtained by applying antiserum which had been preabsorbed overnight with excess inhibin peptide in place of primary antiserum and also normal nonimmune sheep serum as a substitute for primary antiserum. These results provide further evidence that the human corpus luteum is a significant source of immunoreactive inhibin during the normal human menstrual cycle. The specific localization within the granulosalutein cells of the corpus luteum suggests that inhibin alpha-subunit production may originate from a discrete cell population within the human corpus luteum.

Corpus Luteum↗
PubMed1990

Inhibitory effects of treatment with an LHRH antagonist on the ovulatory cycle are reduced when administered during the late follicular phase.

To compare the effects of transitory suppression of pituitary gonadotropin secretion by an LHRH antagonist at the mid or late follicular phase of the menstrual cycle, adult macaques with normal menstrual cycles were treated with an LHRH antagonist (N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10 ]LHRH (detirelix) administered subcutaneously at a dose of 300 micrograms/kg, daily for 3 days beginning either during the mid or late follicular phase. In all eight animals treated during the mid follicular phase, serum concentrations of LH and FSH declined and remained suppressed for 4 days. This caused a fall in serum concentrations of estradiol and the expected ovulation failed to occur. During the recovery period a marked rise in serum FSH occurred followed by normal follicular development and ovulation 14.8 +/- 0.6 days after the last injection of antagonist. Of the 9 macaques given the same treatment during the late follicular phase, only in two was the expected rise in serum progesterone prevented. In 4 of the animals a transitory suppression in LH and estradiol was observed but this was followed by a recovery and occurrence of an LH surge and rise in serum progesterone indicating ovulation during the course of treatment. In the remaining 3 macaques treatment commenced on the day of the initiation of the LH surge and was associated with a progesterone rise of normal duration but lower than normal magnitude during the early luteal phase. These results show that LHRH antagonist treatment causes rapid inhibition of pituitary-ovarian function when administered up to the mid follicular phase of the cycle and is effective in blocking ovulation. The suppressive effects of the antagonist are reduced when administered during the late follicular phase. This may be due to decreased dependence of the pituitary gonadotrope on LHRH at this time and on decreased dependence of the dominant follicle on the gonadotropins.

Animals↗
PubMed1990

Long-term suppression of ovarian function by a luteinizing-hormone releasing hormone agonist implant in patients with endometriosis.

Ten endometriosis patients received luteinizing hormone releasing hormone (LH-RH) agonist (buserelin) implant injections (6.6 mg subcutaneously) at days 0, 42, 84 and 126. Serum LH and follicle-stimulating hormone (FSH) were lowered by day 14. Luteinizing hormone remained at basal concentrations while FSH returned to values in the low-normal range of the menstrual cycle by day 35. At the end of the luteal phase during which treatment commenced, estrone and pregnanediol declined and remained at postmenopausal or early follicular phase values until days 305 to 460. Time to first ovulation ranged from 321 to 481 days after starting treatment. After the initial menstruation, only three instances of bleeding occurred during treatment. Pelvic pain was relieved or markedly reduced by day 42 and remained absent throughout the period of ovarian suppression. These results indicate the potential of a long-acting LH-RH agonist implant to form the basis for the treatment of symptomatic endometriosis.

Administration, Intranasal↗
PubMed1990

Inhibin secretion after treatment with an LHRH agonist and subsequent ovarian hyperstimulation induced by FSH in the macaque (Macaca arctoides).

The effect of ovarian hyperstimulation with 'pure' FSH on serum concentrations of immunoreactive inhibin in macaques in which endogenous gonadotrophin secretion and ovarian activity had been suppressed by an LHRH agonist implant was studied. Four stump-tailed macaques were treated with an LHRH agonist implant in the early follicular phase of the cycle. After a transient stimulatory phase oestradiol secretion was markedly suppressed, and the rises in progesterone and inhibin observed after ovulation were absent. At 8 weeks after implant administration, when serum LH was only just detectable, FSH (Metrodin) was administered to the LHRH agonist-treated macaques once daily for 9 days (75 i.u. on Day 0, 35 i.u. Days 1-8). FSH treatment stimulated a marked increase in oestradiol and immunoreactive inhibin secretion in the absence of a rise in serum progesterone concentrations. Comparison of the FSH-induced pattern of inhibin secretion with the profile during the normal menstrual cycle showed that during the normal cycle inhibin is secreted into the peripheral blood almost exclusively during the luteal phase in the macaque, but stimulation of follicular development by exogenous FSH was associated with a rise in inhibin concentrations in the absence of ovulation. These results suggest that this non-physiological rise in inhibin may be one of the factors involved in the changes in endogenous gonadotrophin secretion which can occur during ovarian hyperstimulation.

Animals↗
PubMed1990

Physiological roles of chicken LHRH-I and -II in the control of gonadotrophin release in the domestic chicken.

The physiological roles of chicken LHRH-I and -II (cLHRH-I and -II) in the regulation of gonadotrophin release were investigated in the domestic chicken. Measurements of the neuropeptides, using specific radioimmunoassays, in brain sections cut in three planes or in grossly dissected brain areas, showed that cLHRH-II occurs in low amounts throughout the brain whereas cLHRH-I is most abundant in the diencephalon. Within the diencephalon, the largest amount of cLHRH-I occurred in the median eminence of the hypothalamus. The amount of cLHRH-I in the median eminence was higher (P less than 0.05) in laying than in out-of-lay hens. No cLHRH-II was detected in the median eminence in either reproductive state. The amount of cLHRH-I in the hypothalamus was increased (P less than 0.05) in cockerels at the onset of puberty and in somatically immature birds after castration. There were no correlated changes in the amounts of hypothalamic cLHRH-II measured in the same experimental samples. Active immunization of laying hens against cLHRH-I but not against cLHRH-II resulted in the complete regression of the reproductive system and a depression in the concentration of plasma LH. These observations, taken together, suggest that gonadotrophin secretion in the hen is more likely to be directly regulated by cLHRH-I than by cLHRH-II.

Animals↗
PubMed1990

Pituitary-testicular function is suppressed by an LHRH antagonist but not by an LHRH agonist in the marmoset monkey.

The use of pituitary desensitization by an LHRH agonist (buserelin) to examine pituitary-testicular function was investigated in a New World primate. Six adult male marmoset monkeys were injected s.c. with an LHRH agonist implant (1.5 mg in a rod 0.5 cm long). Pharmacokinetics, determined by radioimmunoassay of urinary buserelin, revealed a rapid initial release of the agonist followed by a steady decline during a 200-day period. The LHRH agonist treatment resulted in a rapid initial rise in plasma LH followed by a return to mean values similar to those seen in the control samples by 7 days after implantation. Using the present protocol, no evidence of subsequent pituitary desensitization or suppression of testicular function was observed, plasma concentrations of LH and testosterone remaining within the normal range during the 200-day study period. In contrast, pituitary-testicular function was suppressed in the male marmoset after blockade of pituitary LHRH receptors by an LHRH antagonist. Five adults were treated with a single s.c. injection of the antagonist [Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-Ser(Rha)6,AzGlyNH2(10)]-LHRH at a dose of 300 micrograms/kg. The LHRH antagonist induced a marked suppression of plasma LH and testosterone by 6-8 h, the low levels being maintained for 24-48 h. These results show that, whereas treatment with an LHRH antagonist can inhibit pituitary-testicular function in the male marmoset, it may be that desensitization cannot be induced by the LHRH agonist used.

Animals↗
PubMed1990

Inhibin secretion during the ovulatory cycle and pregnancy in the common marmoset monkey.

Changes in plasma concentrations of immunoreactive inhibin in the reproductively cyclic, pregnant and ovariectomized female marmoset monkey (Callithrix jacchus) were measured with a heterologous radioimmunoassay. The pattern of inhibin secretion in five marmosets studied individually during four consecutive cycles was shown to resemble that of progesterone. In these animals, data were pooled according to stage of cycle on the basis of plasma progesterone concentrations. Mean values for inhibin were 5465 and 4972 U/l during the early and late follicular phase. Concentrations rose during the luteal phase to 8431, 12,246 and 12,557 U/l for the early, mid- and late luteal phase respectively. The hormonal profile of inhibin during the normal cycle is similar in both marmoset and stumptailed macaque; however, the marmoset has a 28-fold greater level of inhibin during the luteal phase. In six marmosets in which pregnancy occurred, inhibin concentrations showed no decline at the end of the conceptual cycle and remained increased with respect to the follicular phase throughout the subsequent gestation. Inhibin levels were non-detectable (less than 1000 U/l) in ovariectomized and acyclic marmosets. These results suggest that the corpus luteum is the major source of inhibin in this New World monkey, in common with man and the Old World primates.

Animals↗
PubMed1989

Rapid inhibitory effects of an LHRH agonist implant on the oestrogen-induced LH surge and the induction of a defective luteal phase after an agonist-induced ovulation in the macaque.

Three experiments were performed to evaluate in detail pituitary--ovarian function during the first 21 days after treatment with a luteinizing hormone releasing hormone (LHRH) agonist implant. First, six adult macaques with normal menstrual cycles received an LHRH agonist implant during the late luteal or early follicular phase. To investigate the rapidly of effects on pituitary responsiveness the macaques were treated with 50 micrograms LHRH at the time of implant (day 0) and at days 4, 10 and 21. Effects on serum LH and FSH were determined on basal samples and at 30 and 60 min. At 4 days, LH and FSH were elevated as a result of the implant and no further response to LHRH challenge was observed. By 10 days, LH had returned to the pretreatment range but was unresponsive to the LHRH challenge; by 21 days, LH was lower than the pretreatment range and again LHRH failed to induce a significant response. Serum FSH concentrations also declined during treatment, but in contrast to LH, a significant response to LHRH was observed on day 10. Secondly, the ability to respond to an oestrogen provocation test was examined in six macaques with normal menstrual cycles treated with the LHRH agonist implant during the late luteal or early follicular phase and 7 days later with 50 micrograms/kg oestradiol benzoate in oil s.c. to induce an LH/FSH surge. In control animals, oestrogen treatment resulted in a positive feedback surge, reaching a maximum at 48 h post-injection. In contrast, agonist-treated animals showed complete abolition of the expected increase in LH and FSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Testosterone regulation of proopiomelanocortin messenger ribonucleic acid in the arcuate nucleus of the male rat.

GnRH regulates the secretion of LH and FSH, which stimulate the secretion of testicular hormones. Acting in a reciprocal fashion, these hormones, including testosterone and inhibin, exert a negative feedback effect on GnRH and gonadotropin secretion. Endogenous opioid peptides (EOPs) have been implicated to play a role in steroid-mediated regulation of gonadotropin secretion. In this context, certain steroid hormones (e.g. testosterone) increase EOP activity and ultimately inhibit GnRH secretion; however, the cellular mechanism by which this occurs is unknown. beta-Endorphin is one of these EOPs, and it is derived from a larger precursor molecule, POMC. We tested the hypothesis that testicular hormones and testosterone, in particular, stimulate POMC gene expression in the arcuate nucleus of the male rat brain. First, we compared POMC mRNA levels between intact and castrated male rats. Adult male rats were killed 4 days (n = 4) and 21 days (n = 5) after castration. Intact animals (sham-operated; n = 6) were used as controls. Using in situ hybridization and a computerized image analysis system, we measured the POMC mRNA content in individual cells of the arcuate nucleus. POMC mRNA signal was significantly lower (P less than 0.0003) in both 4-day (126 +/- 2 grains/cell) and 21-day (117 +/- 5 grains/cell) castrates than in controls (142 +/- 2 grains/cell). In a second experiment we tested whether testosterone would reverse the castration-induced loss of POMC message. Again, we castrated animals and immediately implanted them with either empty (sham; n = 6) or testosterone-containing Silastic implants (n = 5) of a size that would deliver physiological levels of testosterone (3.6 +/- 1.5 ng/ml). We observed that testosterone-treated animals had significantly higher levels of POMC mRNA signal (121.8 +/- 3.8 grains/cell) than sham-treated castrates (111.4 +/- 3.6 grains/cell; P less than 0.03) and that the testosterone-treated castrates had POMC mRNA signal levels indistinguishable from those of intact controls (122.0 +/- 1.1 grains/cell). These observations lend credence to the theory that one mechanism by which testosterone may regulate GnRH secretion is by increasing the synthesis of POMC in the arcuate nucleus.

Animals↗
PubMed1989

Luteinizing hormone releasing hormone agonist for contraception in breast feeding women.

During the period of lactation there is a need for a reliable method of contraception since the suppressive effects of lactation on ovulation decline as the duration of breastfeeding is decreased. The aim of this study was to establish that chronic treatment with a LHRH agonist would prevent ovulation throughout the period of lactation and to evaluate the effects of the treatment on estrogen production, bleeding patterns, and nursing practice. Starting 6 weeks postpartum, nine mothers took 300 micrograms LHRH agonist (buserelin), intranasally once daily for the remainder of the duration of breastfeeding [216 +/- 18 days (mean +/- SEM)]. Urinary excretion of LH, estrone, and pregnanediol was compared to that of nine control breastfeeding mothers. In the control subjects follicular development, as assessed by rises in estrone, was minimal during the first 90 days of the study. Thereafter, phases of estrogen secretion were observed. Ovulation occurred in seven of the nine mothers on one to six occasions; time to first ovulation varied from 90-296 days. In the women taking buserelin, LH and estrone were initially stimulated for 1 and 2 weeks, respectively, then declined to basal levels. No ovulations occurred in the treated group. In six treated mothers only minor fluctuations in estrone were observed during the remainder of agonist treatment. In three subjects more frequent and sustained episodes of estrogen secretion were observed, but in contrast to the controls the rises in estrone were not followed by a typical LH surge or a rise in pregnanediol. Bleeding occurred in eight of the nine of the control mothers on one to seven occasions during the study period. The first bleed in five of the mothers was anovular, while other menstrual bleeds occurred in response to falling levels of pregnanediol. Of the mothers taking buserelin, one was amenorrhoeic, and five had only one light bleeding associated with the initial stimulation of estrone. Of the three women with continued fluctuations of estrone, one had three light bleeds, one experienced frequent spotting, while one had regular bleeding. No other side-effects, such as hot flashes or changes in nursing practices, were reported. Our results indicate that LHRH agonist treatment has the potential to be developed as an acceptable method of contraception during the postpartum period. The duration of treatment may be long enough to have a significant effect on maternal-infant well-being without encountering significant problems associated with low estrogen output.

Administration, Intranasal↗