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PubMed1998

On the mechanism of lactational anovulation in the rhesus monkey.

The relative roles of infant suckling and of maternal prolactin (PRL) secretion in lactational anovulation were studied in ovary-intact and ovariectomized rhesus monkeys nursing young that had been removed from their natural mothers. Hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator activity was monitored electrophysiologically in freely behaving animals by radiotelemetry. Serum luteinizing hormone, PRL, estradiol, and progesterone were also measured. Suckling inhibited GnRH pulse generator activity and ovarian cyclicity in all ovary-intact females but had no such effect on the pulse generator in long-term ovariectomized animals. When PRL secretion was suppressed by daily bromocriptine administration, GnRH pulse generator activity remained significantly inhibited and ovulation was prevented in four monkeys (6 trials), whereas in two females (6 trials) a rapid increase in pulse generator frequency and the resumption of ovarian cyclicity were observed although suckling activity was maintained. One monkey displayed both response types. Although these results indicate that suckling per se is able to restrain GnRH pulse generator activity in the absence of PRL, they also suggest that the relative importance of these determinants is variable depending on factors that remain to be determined. The present study also confirms the permissive role of the ovary in the lactational suppression of GnRH pulse generator activity.

Animals↗
PubMed1997

Transvaginal interstitial laser treatment of the ovary for the management of chronic hyperandrogenic anovulation: first clinical experience.

The feasibility of ultrasound-guided transvaginal interstitial laser treatment of the ovary (TILT) and its efficacy for ovulation induction was investigated in 3 hormone-therapy-resistant patients with chronic hyperandrogenic anovulation. TILT was performed at powers of 1-2 W and exposures of 75-600 s. Clear-cut hyperechogenic zones developed during laser irradiation with diameters of up to 13.7 mm. Spontaneous ovulation and/or hormonal changes after TILT did not occur. No adhesion formation was seen during a laparoscopy or laparotomy in 2 patients 6 months after TILT. In conclusion, TILT of the ovaries was simple to perform but so far the clinical results are disappointing. Further studies with a modified technique are necessary to further investigate the efficacy of TILT.

Adult↗
PubMed2005

Polycystic ovaries are common in women with hyperandrogenic chronic anovulation but do not predict metabolic or reproductive phenotype.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unexplained hyperandrogenic chronic anovulation. Experts have recommended including the morphology and volume of the ovary in the diagnostic criteria for PCOS. We performed this study to determine whether there was an association between the morphology and size of the ovaries and markers of insulin sensitivity as determined by dynamic testing within women with PCOS or compared with a group of control women. We then examined reproductive parameters. We studied 88 unrelated PCOS women and 21 control women, aged 17-45 yr. All were in the early follicular phase or its equivalent (no follicle with > 10 mm diameter and anovulatory serum progesterone level < 3 ng/ml). Subjects underwent on the same day a phlebotomy for baseline hormones, a 2-h oral glucose tolerance test, and transvaginal ultrasound to determine the morphology and volume of the ovaries. Ninety-five percent (84 of 88) of women with PCOS and 48% (10 of 21) of the control women had polycystic ovaries using the criteria of at least one ovary greater than 10 cm3 (PCOV) and/or polycystic ovary morphology (PCOM) using the criteria of 10 or more peripheral follicular cysts 8 mm in diameter or less in one plane along with increased central ovarian stroma. PCOM was a better discriminator than PCOV between PCOS and control women. The odds of women with PCOS having PCOM were elevated 50-fold compared with controls (odds ratio, 50; 95% confidence interval, 10-240; P < 0.0001), whereas the odds of PCOV were elevated 5-fold in women with PCOS (odds ratio, 4.6; 95% confidence interval, 1.7-12.6; P = 0.003). Neither the insulin sensitivity index, fasting or 2-h values, or any integrated measures of glucose and insulin varied in women according to either morphology or volume, nor was there an association with circulating androgen levels. Women with PCOS and PCOM had lower FSH levels than women with PCOS and non-PCOM. Women with PCOS and PCOV had a higher LH to FSH ratio than women without PCOV and PCOS. These data support the hypothesis that polycystic ovaries are an abnormal finding. However, neither the morphology nor the volume of the ovaries is associated with distinctive metabolic or reproductive phenotypes in women with PCOS.

Adolescent↗
PubMed1992

Postpartum lactational anovulation in a nonhuman primate (Macaca fascicularis): endogenous opiate mediation of suckling-induced hyperprolactinemia.

The physiological amenorrhea occurring in suckled females has been associated with both hypopulsatile gonadotropin secretion and hyperprolactinemia. To test whether these phenomena are opiate mediated and whether these effects are dependent on the presence of ovaries, we studied six suckled, lactating cynomolgus monkeys, three with intact ovaries and three that were ovariectomized 14 days postpartum. Frequent blood sampling (every 15 min) was performed at approximately monthly intervals using chronic venous catheters accessed remotely via a jacket and tether system. Each monkey was administered saline or naloxone (2 mg bolus then 2 mg/h) by constant infusion, in alternating 6-h blocks. During saline infusions, PRL concentrations varied markedly in a diurnal pattern with concentrations varying from 30-70 micrograms/L during the day and from 100-200 micrograms/L during the night. In both gonadal intact and ovariectomized groups of monkeys naloxone dramatically suppressed and maintained PRL concentrations at less than 20 micrograms/L irrespective of the time of day or the order of administration. The effects of naloxone on gonadotropin concentrations were much less dramatic. In gonadal-intact monkeys, no effect of naloxone was seen on pulse frequency of either FSH or LH, or on mean LH concentration, and only a slight increase was noted in mean FSH concentrations. In ovariectomized monkeys, naloxone was also without effect on pulsatile LH secretion, although mean LH concentrations were slightly higher during naloxone infusions than during saline infusions (P less than 0.05). From these results, we conclude that opiate peptides are released in response to the suckling stimulus in the cynomolgus monkey and that they mediate the effects of suckling on PRL secretion in both gonadal-intact and agonadal cynomolgus monkeys. The lack of effect of opiate blockade on gonadotropin concentrations suggests that multiple pathways may be involved with the inhibition of the GnRH pulse generator during lactational anovulation.

Amenorrhea↗
PubMed1993

Testosterone, a follicular regulator: key to anovulation.

To study the interrelationships of steroids within the follicle, combined 6-h infusions of [3H]dehydroepiandrosterone sulfate and [14C] testosterone ([14C]T) were performed in four normal women treated with menotropins who were undergoing medically indicated surgery. The concentrations of tracer and/or nonisotopic dehydroepiandrosterone sulfate, androst-5-ene-3 beta,17 beta-diol sulfate, androst-5-ene-3 beta,17 beta-diol, dehydroepiandrosterone, androstenedione, T, dihydrotestosterone, estrone (E1), and estradiol (E2) were determined in arterial and venous blood and follicular fluid. The log-transformed product/precursor ratio of [3H]dihydrotestosterone/[3H]T in follicular fluid was negatively correlated with the log-transformed follicular concentrations of E1 (P = 0.01) and E2 (P = 0.02), suggesting a reciprocal relationship between 5 alpha-reductase and follicular E1 and E2. E2 and T were positively correlated in follicular fluid (r = 0.84; P = 0.0003), suggesting a stimulatory action of follicular T on aromatase. These findings along with extensive published data suggest that follicular T functions as a follicular regulator, enhancing follicular aromatase activity when adequate amounts of FSH are available. These conclusions have important implications with regard to mechanisms for selecting the dominant follicle and producing atresia in the remaining cohort of follicles, and they describe a final common path in the pathophysiology of anovulation.

Anovulation↗
PubMed1994

Treatment of anovulation with pulsatile gonadotropin-releasing hormone: prognostic factors and clinical results in 600 cycles.

Pulsatile GnRH (pGnRH) was administered to 292 anovulatory patients in 600 consecutive cycles between February 1984 and February 1993. This represents the largest single pGnRH series ever reported. Patients were divided into the following groups: primary hypogonadotropic amenorrhea (PHA), 73 patients, 161 cycles; other hypogonadotropic hypogonadisms (OHH), 57 patients 107 cycles; multifollicular ovary (MFO), 39 patients 75 cycles; polycystic ovary (PCO), 85 patients 172 cycles; and other hyperandrogenic anovulations (OHA), 38 patients 85 cycles. GnRH was administered iv at a dose of 1.25-20.0 micrograms every 30-120 min; most cycles (505) were performed with a regimen of 2.5-5.0 micrograms GnRH every 60-90 min. In 228 cycles of MFO, PCO, and OHA patients, pGnRH was preceded by GnRH agonist (GnRH-A) suppression. Ovulatory rates were 75%, and pregnancy occurred in 105 cycles (pregnancy rate of 18%/treatment cycle and 23%/ovulatory cycle). Ovulatory and pregnancy rates were higher in PHA, OHH, and MFO and lower in PCO and OHA. Only 4 multiple pregnancies occurred (3.8%), none after GnRH-A suppression. The abortion rate was 30% and was highest in PCO (45%). GnRH-A pretreatment improved ovulatory rates only in PCO (from 49% to 71%; P < 0.001), whereas it had no significant effect on pregnancy and abortion rates in any group. Higher weight and insulin were associated with lower ovulatory and pregnancy rates; higher LH and testosterone were associated with lower ovulatory rates only. We conclude that 1) pGnRH is a highly effective ovulation induction method; 2) pGnRH does not cause ovarian hyperstimulation; 3) low dose pGnRH is associated with a remarkably low incidence of multiple pregnancy; 4) GnRH-A pretreatment improves pGnRH outcome in PCO and further lowers the incidence of multiple pregnancy; 5) pGnRH is associated with relatively elevated abortion rates, particularly in PCO; and 6) pGnRH is less successful in overweight patients and when high baseline LH, testosterone, and insulin levels are present.

Adult↗
PubMed1995

The effect of alprazolam on serum cortisol and luteinizing hormone pulsatility in normal women and in women with stress-related anovulation.

Alprazolam, a benzodiazepine derivative, stimulates specific gamma-aminobutyric acidA receptors and has been found to inhibit CRH activity in the brain. This study examined the effect of alprazolam on serum cortisol and LH pulsatility in six women in the early follicular phase (EFP), six women in the midluteal phase (MLP), and six women with stress-related anovulation (SRA) of normal weight, but with a previous history of anorexia nervosa. Subjects were given alprazolam (2 mg, orally) or an identical placebo capsule at 0900 h, and blood samples were collected through an indwelling venous catheter every 10 min for 8 h in the SRA women and 10 h in EFP and MLP women. Women with SRA were also given clomiphene (100 mg/day) for 5 days before a further 8-h blood sampling session. As expected, there was a diurnal decline in serum levels of cortisol, which was significantly less in women with SRA (55 +/- 4%) than those in both EFP (76 +/- 4%) and MLP women (75 +/- 3%; P < 0.005). The food-related rise of cortisol that follows lunch in normal women was absent in women with SRA. Alprazolam accentuated the decline in serum cortisol, and in all three groups, the mean serum cortisol level after alprazolam treatment was significantly less (P < 0.05) than that after placebo. In SRA women, alprazolam restored visible LH pulses in all women and increased the mean LH pulse frequency (P < 0.02) and pulse amplitude (P < 0.05). This was associated with an increase in mean serum LH from 1.3 +/- 0.3 to 3.0 +/- 0.06 IU/L (P < 0.02). In EFP women, alprazolam reduced the frequency of LH pulsatility from a mean of 5.8 +/- 0.7 to 3.2 +/- 0.5 pulses/10 h (P < 0.02) and increased the mean pulse amplitude from 2.4 +/- 0.5 to 5.0 +/- 1.1 IU/L (P < 0.0005). Alprazolam had no significant effect on LH pulsatility or amplitude in MLP women. To explain this variation in response to alprazolam, we propose that alprazolam accelerates the GnRH pacemaker in SRA women by inhibiting excessive CRH activity, which blocks the GnRH pacemaker in these women. In normal women, we hypothesize that tonic inhibition of the GnRH pacemaker by CRH is minimal, and the reduced pulsatility of LH after alprazolam treatment in EFP women results from inhibition of stimulatory noradrenergic neurons. In MLP women, we propose that preexisting opioid inhibition of noradrenergic neurons by progesterone blocks this effect of alprazolam.

Adolescent↗
PubMed1998

High frequency of luteal phase deficiency and anovulation in recreational women runners: blunted elevation in follicle-stimulating hormone observed during luteal-follicular transition.

The purposes of this investigation were to evaluate the characteristics of three consecutive menstrual cycles and to determine the frequency ofluteal phase deficiency (LPD) and anovulation in a sample of sedentary and moderately exercising, regularly menstruating women. For three consecutive menstrual cycles, subjects collected daily urine samples for analysis of FSH, estrone conjugates (E1C), pregnanediol-3-glucuronide (PdG), and creatinine (Cr). Sedentary (n=11) and exercising (n=24) groups were similar in age (27.0+/-1.3 yr), weight (60.3+/-3.1 kg), gynecological age (13.8+/-1.2 yr), and menstrual cycle length (28.3+/-0.8 days). Menstrual cycles were classified by endocrine data as ovulatory, LPD, or anovulatory. No sedentary women (0%) had inconsistent menstrual cycle classifications from cycle to cycle, but 46% of the exercising women were inconsistent. The sample prevalence of LPD in the exercising women was 48%, and the 3-month sample incidence was 79%. In the sedentary women, 90% of all menstrual cycles were ovulatory (SedOvul; n=28), whereas in the exercising women only 45% were ovulatory (ExOvul; n=30); 43% were LPD (ExLPD; n=28), and 12% were anovulatory (ExAnov; n=8). In ExLPD cycles, the follicular phase was significantly longer (17.9+/-0.7 days), and the luteal phase was significantly shorter (8.2+/-0.5 days) compared to ExOvul (14.8+/-0.9 and 12.9+/-0.3 days) and SedOvul (15.9+/-0.6 and 12.9+/-0.4 days) cycles. Luteal phase PdG excretion was lower (P < 0.001) in ExLPD (2.9+/-0.3 microg/mg Cr) and ExAnov (0.8+/-0.1 microg/mg Cr) cycles compared to SedOvul cycles (5.0+/-0.4 microg/mg Cr). ExOvul cycles also had less (P < 0.01) PdG excretion during the luteal phase (3.7+/-0.3 microg/mg Cr) than the SedOvul cycles. E1C excretion during follicular phase days 2-5 was lower (P=0.05) in ExOvul, ExLPD, and ExAnov cycles compared to SedOvul cycles and remained lower (P < 0.02) in the ExLPD and ExAnov cycles during days 6-12. The elevation in FSH during the luteal-follicular transition was lower (P < 0.007) in ExLPD (0.7+/-0.1 ng/mg Cr) cycles compared to SedOvul and ExOvul cycles (1.0+/-0.1 and 1.1+/-0.1 ng/mg Cr, respectively). Energy balance and energy availability were lower (P < 0.05) in ExAnov cycles than in other menstrual cycle categories. The blunted elevation in FSH during the luteal-follicular transition in exercising women with LPD may explain their lower follicular estradiol levels. These alterations in FSH may act in concert with disrupted LH pulsatility as a primary and proximate factor in the high frequency of luteal phase and ovulatory disturbances in regularly menstruating, exercising women.

Adolescent↗
PubMed1999

Anovulation after precocious pubarche: early markers and time course in adolescence.

Adolescent girls with a history of precocious pubarche (PP) are known to be at increased risk for ovarian hyperandrogenism, an endocrinopathy related to reduced fetal growth, but the characteristics of their ovulatory function have not been fully documented. We assessed ovulatory function by weekly urinary LH and salivary progesterone measurements over 3 consecutive months in 85 adolescent girls with known weight and gestational age at birth: 49 girls had no history of PP (age, 14.7+/-1.7 yr), and 36 had a history of PP (age, 14.4+/-2.0 yr); 55 girls were in the early postmenarcheal phase (0-3 yr after menarche), and 30 were in the late postmenarcheal phase (> 3 yr after menarche). In girls with PP, the 17-hydroxyprogesterone (17-OHP) response to ACTH was determined at prepubertal diagnosis of PP, and serum androgen and gonadotropin concentrations were measured in adolescence together with insulin responses to an oral glucose load. Early postmenarche, the fraction of girls with ovulations was similar in the non-PP and PP subgroups (61% vs. 62%), as was the fraction of ovulatory cycles (25% vs. 22%). Late postmenarche, however, the fractions of ovulating girls and ovulatory cycles were strikingly higher (P < or = 0.001) in the non-PP than in the PP subgroup (91% vs. 20% and 47% vs. 12%). Within the PP subgroup, anovulatory girls were found to have a lower weight SD score at birth (mean+/-SEM) than ovulatory girls (-1.22+/-0.3 vs. -0.36+/-0.3; P = 0.03), a higher 17-OHP response to ACTH before puberty (333.1+/-31 vs. 203.8+/-26 ng/dL; P < 0.002), and, in adolescence, lower serum sex hormone-binding globulin levels and higher circulating LH, free androgen indexes, and insulin responses. In conclusion, these findings indicate that girls with PP are at increased risk for anovulation from late (not early) adolescence onward, particularly those girls with a low weight at birth and/or a high 17-OHP response to ACTH at prepubertal diagnosis of PP.

17-alpha-Hydroxyprogesterone↗
PubMed1996

Identification of anovulation and transient luteal function using a urinary pregnanediol-3-glucuronide ratio algorithm.

The sensitivity and specificity of a urinary pregnanediol-3-glucuronide (PdG) ratio algorithm to identify anovulatory cycles was studied prospectively in two independent populations of women. Urinary hormone data from the first group was used to develop the algorithm, and data from the second group was used for its validation. PdG ratios were calculated by a cycles method in which daily PdG concentrations indexed by creatinine (CR) from cycle day 11 onward were divided by a baseline PdG (average PdG/Cr concentration for cycle days 6-10). In the interval method, daily PdG/CR concentrations from day 1 onward were divided by baseline PdG (lowest 5-day average of PdG/CR values throughout the collection period). Evaluation of the first study population (n = 6) resulted in cycles with PdG ratios > or = 3 for > or = 3 consecutive days being classified as ovulatory; otherwise they were anovulatory. The sensitivity and specificity of the PdG ratio algorithm to identify anovulatory cycles in the second population were 75% and 89.5%, respectively, for all cycles (n = 88); 50% and 88.3% for first cycles (n = 40) using the cycles method; 75% and 92.2%, respectively, for all cycles (n = 89); and 50% and 94.1% for first cycles (n = 40) using the interval method. The "gold standard" for anovulation was weekly serum samples < or = 2 ng/ml progesterone. The sensitivity values for all cycles and for the first cycle using both methods were underestimated because of apparent misclassification of cycles using serum progesterone due to infrequent blood collection. Blood collection more than once a week would have greatly improved the sensitivity and modestly improved the specificity of the algorithm. The PdG ratio algorithm provides an efficient approach for screening urine samples collected in epidemiologic studies of reproductive health in women.

Adult↗
PubMed1981

Occurrence of permanent anovulation in mouse ovaries and permanent changes in the vaginal and uterine epithelia following neonatal treatment with large doses of 5 alpha-dihydrotestosterone.

Female mice of the C57BL/Tw strain were injected daily with 1 microgram estradiol-17 beta (E2), 1 or t microgram testosterone (T) and 5 alpha-dihydrotestosterone (5 alpha-DHT), the dose being increased varying from 5 to 100 microgram for 5 days from the day of birth. These mice were ovariectomized at 90 days of age and kept for 50 days until sacrifice. Permanent-anovulatory ovaries were found in 30-40% of mice treated neonatally with large doses of 5 alpha-DHT. All of the E2-treated and 42% of the 5 microgram T-treated mice showed permanent anovulation in the ovaries at 90 days of age, while none of the 1 microgram T-treated mice had such anovulatory ovaries. Estrogen-independent, permanent vaginal changes occurred in mice receiving injections of 5 microgram T or 5-100 microgram 5 alpha-DHT, but not in those given the injections of 1 microgram T.

Animals↗
PubMed1991

Spontaneous anovulation causing disappearance of cyclical symptoms in women with the premenstrual syndrome.

In the premenstrual syndrome the negative symptoms appear during the luteal phase of the menstrual cycle. Ovulation and the formation of a corpus luteum seem to be of great importance in precipitating the syndrome. In a large group of women with premenstrual syndrome investigated daily with symptom ratings and weekly plasma estradiol and progesterone assays, 8 were found to have one ovulatory and one spontaneously occurring anovulatory menstrual cycle. In both these cycles, the post- and premenstrual phases were compared by testing for recurrence of symptoms. All patients showed a highly significant cyclical worsening of negative premenstrual symptoms during the ovulatory cycles, whereas in the anovulatory cycles the cyclical symptoms disappeared, resulting in relief of the premenstrual syndrome. These results support earlier hypotheses, suggesting that the premenstrual syndrome appears as a result of provoking factors produced by the corpus luteum. This view is in line with earlier therapeutic findings showing that induced anovulation can relieve the premenstrual syndrome.

Adult↗
PubMed1976

Serum corticosterone in rats with delayed anovulation.

The purpose of this study was to investigate adrenal function in rats during the development of persistent oestrus to determine whether a change in blood levels of corticosterone would precede or coincide with the onset of infertility. The syndrome of delayed persistent oestrus and anovulation was induced by administration of a low dose (10 mug) of testosterone propionate (TP) at 5 days of age. Control animals were handled without injection or received the vehicle (sesame oil) only. Half of each group was ovariectomized at weaning and received Silastic implants of either oestradiol benzoate (OB) or cholesterol, 3 mm tube length/100 g body weight. Intact rats given the low TP dose showed precocious vaginal opening (27.3 +/- 2.1 days v. 37.6 +/- 2.4 (S.E.M.) days in unhandled controls) and ovulated within 2 days. Persistent vaginal cornification developed in 22 out of 26 rats by 75 days of age. The TP-treated rats had higher corticosterone values than the controls and did not show a further increase after OB implantation. Cholesterol implantation depressed corticosterone levels in the TP-treated rats. The effects of the low TP dose were not dependent upon gonadal function since they persisted in ovariectomized rats. The results suggest that early exposure to androgen can modify the sensitivity of the adrenal system to oestrogen, and can also lead to persistently high values of corticosterone which are not depressed by ovariectomy. These changes precede the onset of persistent oestrus.

Adrenal Glands↗
PubMed1999

Twice daily suckling but not milking with calf presence prolongs postpartum anovulation.

Two experiments were conducted to determine whether milking beef cows two or five times daily in the presence or absence of their own nonsuckling calves would alter postpartum interval to first ovulation. Multiparous Angus x Hereford cow-calf pairs were assigned randomly between 13 and 18 d postpartum to treatments for 4 wk. In Exp. 1, pairs were assigned to six treatments: 1) calf was weaned permanently from its dam (CW; n = 9); 2) same as CW, but dam was milked twice daily (CW+2xM; n = 9); 3) calf was present continuously with its dam but restricted from contact with the udder (CR; n = 9); 4) same as CR, but dam was milked twice daily (CR+2xM; n = 9); 5) same as CR, but calf was allowed to suckle twice daily (CR+2xS; n = 8); and 6) calf was present continuously with its dam and suckled ad libitum (CP; n = 9). The interval from onset of treatments to first postpartum ovulation was shorter (P<.05) in the CW (14.1+/-3.1 d), CR (14.2+/-3.1 d), CW+2xM (13.0+/-3.1 d), and CR+2xM (17.2+/-3.1 d) than in the CP (34.7+/-3.1 d) and CR+2xS (33.9+/-3.3 d) treatments. Daily milk yield during treatment was greater (P<.01) for CR+2xM cows (7.1+/-.6 kg) than for CW+2xM cows (3.5+/-.6 kg). In Exp. 2, cow-calf pairs were assigned to three treatments: 1) CR+2xM (n = 10); 2) same as CR+2xM but cows were milked five times daily (CR+5xM; n = 10); or 3) CP (n = 10). The interval to first postpartum ovulation was shorter (P<.05) in the CR+2xM (23.6+/-3.5 d) and CR+5xM (26.1+/-3.7 d) treatments than in the CP (37.7+/-3.7 d) treatment. Daily milk yield during treatment was greater (P<.05) for CR+5xM cows (7.7+/-.6 kg) than for CR+2xM cows (6.4+/-.6 kg) by 17%. We conclude that suckling twice daily was sufficient to prolong postpartum anestrus as much as suckling ad libitum. Furthermore, milk removal by suckling, but not by milking two or five times daily, even in the presence of the cow's own nonsuckling calf, is essential to prolong postpartum anovulation.

Animals↗
PubMed1989

Daily measurements of salivary progesterone reveal a high rate of anovulation in healthy students.

Daily concentrations of salivary progesterone (P) were measured from 32 women during a complete menstrual cycle. Seventeen of the subjects were university students and 15 were patients of an infertility clinic (a severe male-factor was verified as the cause of infertility in all of them). Commercially available reagents for radio-immunoassay of serum P were modified for salivary measurements, to yield acceptable precision and sensitivity (40 pmol/l). Good correlation (r = 0.93) was found between salivary and serum P concentrations in samples collected simultaneously. The follicular phase levels of salivary P were below 100 pmol/l, and those at the luteal peak were 390 +/- 45 pmol/l (mean +/- SEM, n = 24). From the menstrual salivary P concentration curves we identified the first day of significant elevation above mean follicular levels (T2) and thereafter calculated the cumulative sum of daily P concentrations until 95% of the luteal phase secretion had accumulated (C95). The time needed to reach C95 (designated T95) and logC95 were plotted in coordinates and used as the basis of evaluation of normal menstrual P secretion. The observations were distributed in two groups, one with clearly identifiable T2 and a distinct luteal-phase P (ovulation had occurred) and one with no identifiable T2 and absent luteal-phase P peak (indicative of anovulation). Interestingly, 47% of the student population had an abnormally low menstrual P profile while all the other subjects displayed a clear luteal-phase peak of salivary P. These data provide more evidence for applicability of salivary P measurements for diagnosis of corpus luteam function and highlight the difficulty of selecting representative reference populations in studies on female reproductive endocrinology.

Adult↗
PubMed1998

Ovulation induction with pulsatile GnRH in a patient with anovulation of hypothalamic origin and central diabetes insipidus.

Patients with diabetes insipidus (DI) are at high risk for dehydration, hypernatremia and hemodynamic instability. Ovarian hyperstimulation syndrome (OHSS) likewise has negative effects on electrolyte balance. If ovulation induction is required in a patient with DI, there is thus a strong argument for avoiding techniques that increase the risk of OHSS. This paper reports the results of ovulation induction in a patient with anovulation of hypothalamic origin and central (vasopressin deficit) DI. Ovulation was induced with pulsatile gonadotropin-releasing hormone (GnRH), which induces single-ovule cycles and which does not increase the risk of OHSS. The patient successfully achieved pregnancy after seven ovulatory cycles.

Adult↗
PubMed1991

Lactational [correction of Lacational] anovulation in rats and its dependency on progesterone.

The relationship between prolactin (PRL) secretion and anovulation in lactating rats was studied. Normal lactating rats and lactating rats treated with antiserum against luteinizing hormone-releasing hormone at the time of postpartal ovulation were used. Normal lactating rats were treated with either a dopamine agonist (CB-154, 150 micrograms/rat) on Day 10 or 13, or pups removal on Day 7 or 10, and thereafter luteolysis and inhibition on PRL secretion were assessed. With the CB-154 treatment, the incidence of luteolysis increased as the lactational period advanced (42% vs 72%), whereas it decreased (73% vs 14%) with the pups removal. Thus, dopamine effectively inhibited PRL secretion during the later lactational stage, but could not do so during the earlier stage when there were mechanisms other than dopamine stimulating PRL secretion. Following luteal regression induced by CB-154, ovulation did not occur if the rats were treated with CB-154 on Day 10, whereas 50% of the rats ovulated within 4 days if treated on Day 13. Furthermore, in the lactating rats treated with anti-luteinizing hormone-releasing hormone serum during late pregnancy, ovulation was not observed until Day 10 of lactation. Since the serum progesterone levels were low in these rats due to the absence of ovulation and lactational corpora lutea, the blockade of ovulation was not due to elevated circulating progesterone during the early lactational period. The mechanism of ovulation blockade during lactation thus seems to shift from being progesterone independent to progesterone dependent at a similar period when the neuroendocrine control of PRL secretion shifts from dopamine independent to dependent.

Animals↗
PubMed1976

Analysis of variables in treatment of anovulation with human gonadotrophins.

Twenty seven women with anovulation were given 121 courses of gonadotrophins monitored by excretion of estrogen and pregnanediol. The FSH, ovulating dosage of HCG, time interval between FSH and HCG and subsequent supporting doses of HCG were varied in a statistical design. None significantly affected ovulation or pregnancy rates. The preparation with an FSH:LH ratio of 1 required a lower dosage to initiate an estrogen response than that with a ratio of 5. After adjustment it still produced a faster rise in estrogen excretion. The amount of estrogen also varied with the time interval between FSH and HCG, the ovulating dose of HCG and supporting doses of HCG. The amount of pregnanediol varied with the ovulating dose of HCG and the length of the luteal phase varied with the ovulating dose of HCG and supporting injections of HCG. The dosage of FSH needed to initiate a response increased on average by 8% from one course to the next. Simplicity, economy and risk of multiple pregnancy are discussed in relation to these variables.

Adult↗