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[The mechanism of induction of ovulation by bromocriptine in euprolactinemic anovulation--the role of occult hyperprolactinemia in anovulation].

It has been well documented that ovulation was induced by Bromocriptine treatment in euprolactinemic anovulation. The present study has been carried out to clarify the underlying mechanism. 28 patients with euprolactinemia (PRL less than 25 ng/ml) were treated with a 5 mg daily administration of Bromocriptine. Ovulation was induced in 13 cases, which were determined by their BBT charts. In the ovulated cases, PRL secreting capacities were increased, determined by TRH administration. On the other hand, PRL secreting capacities were normal in the anovulated cases. The studies of the circadian secretion of PRL revealed that a nocturnal hyperprolactinemic state occurred for several hours in the ovulated cases, which was not seen in the anovulated cases. From these results, the mechanism of induction of ovulation by Bromocriptine in euprolactinemic anovulation exists on the suppression of the increased PRL secreting capacity, which may be related to the occulted hyperprolactinemia at night. Ovulated cases by Bromocriptine are seemingly euprolactinemia, but in truth they may be a kind of hyperprolactinemia.

Adult↗

Recombinant follicle-stimulating hormone (FSH; Puregon) is more efficient than urinary FSH (Metrodin) in women with clomiphene citrate-resistant, normogonadotropic, chronic anovulation: a prospective, multicenter, assessor-blind, randomized, clinical trial. European Puregon Collaborative Anovulation Study Group.

OBJECTIVE: To compare the safety and efficacy of recombinant FSH (follitropin beta, Puregon; NV Organon, Oss, the Netherlands) and urinary FSH (urofollitropin, Metrodin; Ares-Serono, Geneva, Switzerland). DESIGN: A prospective, multicenter, assessor-blind, randomized, clinical trial. SETTING: Twelve European infertility clinics. PATIENT(S): One hundred seventy-two women (recombinant FSH: n = 105; urinary FSH: n = 67) with clomiphene citrate-resistant normogonadotropic chronic anovulation (World Health Organization group II). INTERVENTION(S): Eligible subjects were randomized (ratio of recombinant to urinary FSH, 3:2) and treated for a maximum of three cycles. A low-dose step-up regimen was used, with 75 IU of FSH given IM daily for a maximum of 14 days and, if needed, weekly increments of half an ampule given thereafter until the threshold dose for follicular development was achieved. MAIN OUTCOME MEASURE(S): Cumulative ovulation rate after three cycles, total FSH dose, and treatment period needed to achieve ovulation. RESULT(S): The cumulative ovulation rates after three treatment cycles were 95% and 96% for the recombinant and urinary FSH groups, respectively. Overall, ovulation was seen in 155 of 223 treatment cycles (69.5%) in the recombinant FSH group, compared with 92 of 138 treatment cycles (66.7%) in the urinary FSH group. In the first cycle, a statistically significantly lower total dose (750 versus 1,035 IU) and a shorter treatment period (10 versus 13 days) were needed in the recombinant FSH group to reach ovulation. Only one case of ovarian hyperstimulation syndrome led to hospitalization. Two sets of twins (one in each treatment group) and one set of triplets (in the recombinant FSH group) were born. CONCLUSION(S): Recombinant FSH (Puregon) is more efficient than urinary FSH (Metrodin) in inducing follicular development.

Adult↗

Progestogens versus oestrogens and progestogens for irregular uterine bleeding associated with anovulation.

BACKGROUND: Dysfunctional uterine bleeding (DUB) is "excessively heavy, prolonged or frequent bleeding of uterine origin which is not due to pregnancy or to recognizable pelvic or systemic disease". Anovulation may be inferred from a number of observations but in the normal clinical situation, anovulation is often assumed when a woman presents with heavy, prolonged or frequent bleeding, particularly in those at the extremes of reproductive life and in women known to have the polycystic ovarian syndrome. Menstrual bleeding that is irregular or excessive is usually poorly tolerated by the majority of women. Changes in the length of the menstrual cycle generally imply disturbances of the hypothalamo-pituitary-ovarian (HPO) axis. In anovulatory DUB with acyclic (irregular) oestrogen production there will be no progesterone withdrawal from oestrogen primed endometrium and so cycles are irregular. Prolonged oestrogen stimulation may cause a build up of endometrium with erratic bleeding as it breaks down and is expelled. This is the rationale for using cyclical progestogens during the second half of the menstrual cycle in order to provoke a regular withdrawal bleed. Continuous progestogen is intended to induce endometrial atrophy and hence to prevent oestrogen-stimulated endometrial proliferation. Progestogens, and oestrogens and progestogens in combination are already widely used in the management of irregular or excessive bleeding due to DUB, but the regime, dose and type of progestogen used varies widely with little consensus about the optimum treatment approach. OBJECTIVES: To determine the effectiveness and acceptability of progestogens alone, and oestrogens and progestogens in combination in the management of irregular bleeding associated with anovulation. SEARCH STRATEGY: The search strategy of the Menstrual Disorders Group was used to identify all randomised trials of progestogens alone or in combination with oestrogens in the management of irregular menstrual bleeding associated with anovulation. In addition a search of the Cochrane Controlled Trials Register was undertaken. SELECTION CRITERIA: All randomised controlled trials of progestogens (via any route) alone or in combination with oestrogens in the treatment of irregular bleeding associated with anovulation. DATA COLLECTION AND ANALYSIS: Study quality assessment and data extraction were carried out independently by two reviewers. Both reviewers were experts in the content matter. MAIN RESULTS: No randomised trials were identified which compared progestogens with oestrogens and progestogens in the management of irregular bleeding associated with anovulation. Only one small, non-randomised study compared two progestogen regimes in the management of heavy and irregular bleeding in subjects with confirmed anovulation. One randomised study compared the effects of two progestogens on endometrial histology in subjects with a variety of menstrual symptoms, half of whom had cystic glandular hyperplasia. No studies were found which compared progestogens with oestrogens and progestogens in combination or with placebo in the management of irregular bleeding associated with anovulation. REVIEWER'S CONCLUSIONS: There is a paucity of randomised studies relating to the use of progestogens and of oestrogens and progestogens in combination in the treatment of irregular bleeding associated with anovulation. Further research is needed to establish the role of these treatments in the management of this common gynaecological problem.

Adult↗

Does anovulation induced by oral contraceptives favor pregnancy during the following two menstrual cycles?

OBJECTIVE: To compare IVF and pregnancy outcomes before and after anovulation induced by oral contraceptives. DESIGN: Observational clinical study. SETTING: Infertility clinic. PATIENT(S): Forty women with two intact ovaries (32 of 40 couples with male factor infertility and 8 with unknown causes of infertility) underwent 190 IVF treatment cycles (55 natural cycles and 135 clomiphene citrate-stimulated cycles). INTERVENTION(S): If the women failed to conceive after 2-4 IVF treatment cycles, oral contraceptives were used to induce anovulation for 1 month before IVF was performed in two consecutive cycles. MAIN OUTCOME MEASURE(S): Rates of oocyte retrieval, fertilization, cleavage, preembryo formation, pregnancy, and implantation were compared before and after a period of anovulation. RESULT(S): The pregnancy rate per cycle of the first and second cycle combined (23%) and that of the second cycle alone (30%) after a period of anovulation were significantly higher than that observed before a period of anovulation (9%). CONCLUSION(S): Anovulation induced by oral contraceptives, showing bilateral ovarian quiescence, enhances pregnancy rates in the following two menstrual cycles of IVF treatment.

Adult↗

Bayesian analysis of risk factors for anovulation.

Two algorithms for assessing ovulatory status using daily urinary levels of oestrogen and progesterone metabolites have been applied to non-clinic-based, free-living populations of women. These relatively new methods for assessing ovarian function have been used to assess the potential adverse effects of occupational and environmental exposures, such as smoking, on the reproductive health of women. One algorithm has been validated against serum hormone measurements and gives good sensitivity and specificity for anovulation. However, a gold standard is generally not available in epidemiologic field studies in which these daily urine samples are collected. In this paper, we used Bayesian methods to estimate: (i) the probability of occurrence of anovulation, (ii) the sensitivity and specificity of the two algorithms, and (iii) the association between anovulation and smoking and other risk factors in the absence of a perfect test. We evaluated the two published algorithms for assessing ovulatory status, based on their cross-classified results applied to one randomly selected cycle from each woman in a sample of 338 employed women. We first assumed that the algorithms were independent, conditional on ovulatory status. Then, we used a dependence model to allow for correlation between the results of the two algorithms. We implemented a Bayesian logistic regression analysis that allowed the outcome measurement to be partially imperfect. We incorporated the posterior distributions for algorithm accuracy obtained from the dependence model as prior distributions for this logistic regression model. Then, we compared the results with those obtained from a standard multiple logistic approach using the algorithm determination of ovulatory status as if it were perfect. Our results indicated that increasing physical activity was associated with a significantly increased risk of anovulation; and smokers had a potentially, but not statistically significant, increased occurrence of anovulation.

Adult↗

Are there two types of postpill anovulation?

Anovulation, indicated by requiring treatment with clomiphene or gonadotropins to conceive, was studied in a cohort of 16,583 women interviewed postpartum. There were 2,853 former oral contraceptive users, and 2.2% of them reported anovulation, compared with 2.7% of controls. Among primigravidas, the rates were 4.2% and 4.4% in pill users and controls, respectively. A statistically significant excess of anovulation was reported by former pill users who had been underweight in relation to their height at the time of conception. Independently of pill use, the condition tended to be associated with obesity. Data from this and previous studies suggest that there may be two distinct entities of postpill anovulation: the first, identical with spontaneous secondary anovulation; the second, occurring in slender women who have used oral contraceptives. These findings need confirmation from prospective studies using standard diagnostic criteria.

Adult↗

Women with functional hypothalamic amenorrhea but not other forms of anovulation display amplified cortisol concentrations.

OBJECTIVE: To test the hypothesis that increased cortisol secretion is specific to women with decreased GnRH drive and not found in eumenorrheic women or those with other causes of anovulation. DESIGN: Cortisol concentrations in blood were determined at 30-minute intervals for 24 hours in three well-characterized groups: women with functional hypothalamic amenorrhea, those with other causes of anovulation, and eumenorrheic women. SETTING: Academic medical center. PATIENT(S): Women aged 20 through 35 years, with well-defined reproductive states. INTERVENTION(S): Venous blood samples were obtained from, and psychometric inventories were completed by, the participants. MAIN OUTCOME MEASURE(S): Twenty-four-hour cortisol levels, 24-hour LH pulse patterns, and serial P levels were measured in women with functional hypothalamic amenorrhea, eumenorrheic women, and those with other causes of anovulation. RESULT(S): Cortisol secretion was higher in women with functional hypothalamic amenorrhea (n = 19) than in those with other causes of anovulation (n = 19) or eumenorrheic women (n = 19). Six women who recovered from functional hypothalamic amenorrhea had cortisol levels comparable to those of eumenorrheic women and those with other causes of anovulation. CONCLUSION(S): These data underscore the association between increased hypothalamic-pituitary-adrenal activity and reduced GnRH drive and support the concept that functional hypothalamic amenorrhea develops in response to stress-induced alterations in central neural function that modify hypothalamic function.

Adult↗

Differential expression of T-helper cytokines in the peritoneal fluid of women with normal ovarian cycle compared with women with chronic anovulation.

BACKGROUND: Estrogen and progesterone immunoregulate the genital environment by expression of cytokines and growth factors. OBJECTIVE: To investigate the pattern of expression of T-helper cytokines during the ovarian cycle compared with women with chronic anovulation resistant to clomiphene citrate. HYPOTHESIS: Expression of T-helper cytokines in women with chronic anovulation may be different from the pattern in women with a normal ovarian cycle. METHODS: We evaluated 31 infertile women having laparoscopy for evaluation of tubal patency and evidence of ovulation in two groups during (a) the luteal phase (17 women) and (b) the follicular phase (14 women). A third group was composed of 14 women with polycystic ovarian syndrome, but they were resistant to clomiphene citrate for induction of ovulation and had laparoscopic ovarian cautery. Peritoneal fluid was collected during laparoscopy. Estimation of T-helper cytokine interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, IL-4 and IL-6 in serum, peritoneal fluid and culture of the peritoneal mononuclear cells was performed by ELISA. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, estradiol and progesterone were evaluated by the Vidas Parametric System. RESULTS: The LH : FSH ratio was significantly higher in the women with polycystic ovaries than in the ovulatory groups. IL-2 and IFN-gamma were more highly expressed in the follicular phase but the T-helper 2 cytokines IL-4 and IL-6 predominated in the luteal phase, serum, peritoneal fluid and culture of the peritoneal mononuclear cells. From the follicular to the mid-luteal phase, IL-6 increased three to fivefold in the serum and peritoneal fluid, but there was low expression with anovulation. CONCLUSIONS: The peritoneal fluid levels of IL-4 and IL-6 are higher in the luteal phase. Low IL-6 levels in chronic anovulation may be a marker of resistance to clomiphene citrate.

Adult↗

The use of a decremental dose regimen in patients treated with a chronic low-dose step-up protocol for WHO Group II anovulation: a prospective randomized multicentre study.

BACKGROUND: In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10-13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol. METHODS: Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10-13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles >or=16 mm in diameter were present and/or serum estradiol (E(2)) values were <1200 pg/ml. The primary outcome measure was the number of follicles >or=16 mm in size at the time of hCG administration. RESULTS: Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (>/=16 mm: 1.5 +/- 0.9 versus 1.4 +/- 0.7, respectively). Furthermore, serum E(2) levels were equivalent in the two groups at the time of hCG administration (441 +/- 360 versus 425 +/- 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy. CONCLUSIONS: The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation.

Anovulation↗

Effect of acute nutritional restriction on incidence of anovulation and periovulatory estradiol and gonadotropin concentrations in beef heifers.

The effects of acute nutritional restriction on follicular dynamics, incidence of anovulation, and periovulatory estradiol and gonadotropin concentrations were studied in two replicates using beef heifers exhibiting regular estrous cycles. Heifers fed a diet supplying 1.2 maintenance (1.2 Mn) were synchronized using an intravaginal progesterone-releasing device for 8 days. One day before device removal, heifers were allocated randomly, within replicate, to a diet supplying 0.4 Mn (n = 20), or kept at 1.2 Mn (n = 21). On the sixth day after detected ovulation, heifers received 500 microg of synthetic prostaglandin F(2alpha) (PGF(2alpha)) to induce luteolysis, estrus, and ovulation of the first dominant follicle (DF). Animals were inseminated and returned to a diet of 1. 2 Mn. Pregnancy diagnosis was performed 30 days later. The maximum diameter subsequently attained by the DF present at progesterone withdrawal was smaller (P < 0.01) in heifers fed 0.4 Mn. Two heifers fed 0.4 Mn failed to ovulate this DF (P > 0.10). Growth rate (P < 0. 01) and maximum diameter (P < 0.001) of the DF in the first follicular wave of the next estrous cycle was also reduced in heifers fed 0.4 Mn. After prostaglandin administration, a further 10 heifers fed 0.4 Mn failed to ovulate the first DF of this cycle, and it regressed (P < 0.001), causing anovulation in 12 of 20 heifers within 13-15 days (P < 0.001). Anovulation of the DF present at progesterone withdrawal was preceded by a proestrous estradiol increase but absence of a gonadotropin surge (2 of 2 heifers), while neither endocrine event was detected before anovulation of the DF of the first new follicular wave (2 of 2 heifers). In cases in which ovulation of the first DF of the new cycle occurred, fertility was similar (P > 0.10) in heifers fed either 0.4 (n = 7) or 1.2 Mn (n = 20). In conclusion, acute nutritional restriction of cyclic heifers from 1.2 to 0.4 Mn decreased the growth rate and maximum diameter of DFs and induced failure of the DF to ovulate in 60% of heifers, but, within the confines of limited animal numbers, did not compromise fertility in heifers that ovulated.

Animal Nutritional Physiological Phenomena↗

Influence of exogenous gonadotropin-releasing hormone on ovarian function in beef cows after short- and long-term nutritionally induced anovulation.

The effect of pulsatile infusion of gonadotropin-releasing hormone (GnRH) on follicular function was evaluated in nutritionally induced anovulatory beef cows. After 4 (short; n = 12) or 18 wk (long; n = 12) of anovulation, cows were randomly assigned within anovulatory group to either 2 microg of GnRH treatment or saline (control; i.v.) every hour for 5 d. Ovarian structures were monitored by daily ultrasonography. Growth rate of the largest follicle (P < 0.01) and maximal size of the largest follicle during treatment were greater (P < 0.01) for GnRH vs control cows. At exsanguination after 5 d of GnRH treatment, the size of the second-largest follicle was greater (P < 0.05) in short (i.e., 4 wk) anovulatory cows than in long (i.e., 18 wk) anovulatory cows and the largest follicle tended (P < 0.10) to be larger in long vs short anovulatory cows. Short anovulatory GnRH-treated cows had more small follicles than short anovulatory control cows or long anovulatory GnRH-treated or control cows (anovulation x GnRH; P < 0.10). Follicular fluid (FFL) concentrations of estradiol (P < 0.01) and androstenedione (P < 0.05) were greater in GnRH vs control cows. Concentrations of insulin-like growth factor-I were greater (P < 0.10) in large vs small follicles in cows that were anovulatory for 4 wk, but not in cows that were anovulatory for 18 wk. The amount of insulin-like growth factor-binding protein (IGFBP)-3 in FFL was greater (P < 0.05) in 4- vs 18-wk anovulatory cows. Amounts of IGFBP-2, -4, and -5 were greater (P < 0.001) in FFL of small (< 5 mm) vs large (> or = 5 mm) follicles regardless of treatment. We conclude that pulsatile treatment with GnRH for 5 d stimulates similar growth of the largest follicles in short- and long-term anovulatory beef cows, and that the duration of anovulation is not a major factor that limits follicular growth w hen anovulatory cowsare treated with GnRH. The primary intrafollicular factors associated with increased follicular size were increased concentrations of estradiol, progesterone, and insulin-like growth factor-I,and decreased concentrations of IGFBP-2, -4, and -5. Increased duration of anovulation was associated with decreased concentrations of IGF-I and IGFBP-3 in FFL.

Androstenedione↗

Plasma hormone profile in anovulation.

Daily plasma hormones, including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrone (E1), estradiol (E2), progesterone, androstenedione, and testosterone (T), were measured in 16 anovulatory patients for a span of 3 to 4 weeks. The clinical diagnoses in this group of patients included the following: anovulation-eumenorrhea (n = 5), anovulation-polymenorrhea (n = 1), anovulation-oligomenorrhea (n = 3), congenital adrenal hyperplasia (n = 1), polycystic ovarian disease (n = 4), severe hypothalamic amenorrhea (n = 1), and postpartum amenorrhea-galactorrhea (n = 1). Follicular activity was evident in polymenorrheic and oligomenorrheic patients, and menstruation occurred in these patients following estrogen withdrawal. No follicular maturation was noted in the group of patients with anovulation-eumenorrhea, and menstruation in these patients was considered breakthrough bleeding. Low FSH levels were observed in anovulatory patients with eumenorrhea, polymenorrhea, and oligomenorrhea. Significantly high LH values were noted in both classic and non-classic polycystic ovarian disease. Extremely low E1 and E2 levels were found in patients with severe hypothalamic amenorrhea and postpartum amenorrhea-galactorrhea. Slightly elevated progesterone levels were observed in polymenorrheic and oligomenorrheic patients prior to menstruation; this was frequently associated with an LH surge or elevation. Elevated T levels were consistently associated with hirsutism but not with obesity.

Adolescent↗

Anovulation with estrogen production: receptor disorders?

Receptor antibodies have been implicated in the pathogenesis of several autoimmune disorders such as Graves disease. The authors hypothesized that serum antibodies against the luteinizing hormone (LH) receptor existed in women with chronic anovulation syndrome and continuously stimulated the ovaries. Twenty patients with the clinical diagnosis of anovulation with estrogen production were studied. The effects of serum globulins on the binding of 125I-labeled human chorionic gonadotropin (hCG) to ovarian receptors in the patients were compared with the effects in age-matched controls. These studies did not demonstrate significant inhibition of 125I-hCG binding to ovarian receptors by immunoglobulins of patients with anovulation and estrogen production in comparison with those of control subjects. This finding suggests that the cause of anovulation with estrogen production is not an autoimmune phenomenon involving the LH receptor of the human ovary.

Adenylyl Cyclases↗

[Effects of bromocriptine on FSH and LH secretion in women with euprolactinemic anovulation (author's transl)].

A few reports have been given that Bromocriptine effected not only on the hyperprolactinemic anovulations but also on the euprolactinemic anovulations. This study was performed to examine the underlying mechanism, 5 mg of Bromocriptine was daily administered for 30 days to 38 women with euprolactinemic anovulations. The basal secretions of FSH, LH and Prolactin and also the responsiveness to LH-RH, TRH and estradiol were examined. 31.6% of oligomenorrhea, anovulatory cycle and Ist. grade amenorrhea showed ovulatory cycles, however, no ovulations were observed in IInd. grade amenorrhea. The basal levels of FSH and LH significantly increased but the basal levels of Prolactin decreased by Bromocriptine. The responsiveness of FSH to LH-RH was markedly promoted but LH showed no significant change. Serum FSH was suppressed in estrogen loading test after Bromocriptine, which was poorly changed before. On the other hand, serum LH was markedly elevated by estradiol after Bromocriptine, which showed poor elevation before. These results conclude that: 1) Ovulation is induced by Bromocriptine administration in euprolactinemic anovulations. 2) Bromocriptine promotes the FSH and LH secretion from the pituitary and also promotes the reserve of FSH in the pituitary. 3) Bromocriptine promotes the sensitivity of the estrogen feedback in the hypothalamus.

Adolescent↗

Clinical and hormonal characteristics in women with anovulation and insulin-treated diabetes mellitus.

Clinical characteristics and basal hormonal parameters related to ovulatory function were investigated in 22 diabetic patients with anovulation (group 1) and in nine normally menstruating diabetic patients (group 2) and 45 nondiabetic patients with anovulation (group 3). No significant differences according to control of the diabetes were demonstrated within the two diabetic groups. Groups 1 and 3 did not differ according to classification of anovulation. Group 1 had significantly (P less than 0.01) lower levels of prolactin (PRL), 17 beta-estradiol (E2), thyrotropin (TSH), 3,3',5-triiodothyronine (T3), and thyroxine (T4) than those of group 3, and significantly (P less than 0.01) lower levels of E2 and TSH than those of group 2. The urinary excretion of cortisol was significantly higher in group 1 than in group 2 (P less than 0.05) and group 3 (P less than 0.01). These data suggest a derangement in pituitary-gonadal feedback mechanisms or a depression of pituitary function in anovulatory diabetic patients, and we hypothesize that an increased central/peripheral dopamine and/or cortisol activity in these patients may to some extent influence the hypothalamic-pituitary axis.

Adolescent↗

The association between pituitary adenomas and chronic anovulation syndrome.

A cohort of 487 patients with chronic anovulation syndrome diagnosed between January 1, 1970, and January 1, 1980, were followed up to determine the frequency of pituitary adenomas among them. Of the 487 patients, four (0.8%) had pituitary adenoma. This compares with an expected number of 0.42, yielding a relative risk of 9.5 (95% confidence interval, 2.6 to 24.3). Within this cohort, the prevalence rate was 2.7% for galactorrhea and 3.3% for hyperprolactinemia. The prevalence rate of abnormal radiologic findings was 6.4% for roentgenography of the sella, 25.4% for sellar tomography, and 14.7% for computed tomography. In addition, 15 patients with pituitary adenomas and 60 control subjects were compared for prior anovulation syndrome. The relative risk of pituitary adenomas for patients with chronic anovulation syndrome in this case-control study was 24.3 (95% confidence interval, 4.9 to 120.6).

Adenoma↗

Lactational anovulation in non-human primates: restriction of nursing inhibits Prl secretion without precipitating the return of ovulatory menstrual cyclicity in cynomolgus monkeys.

To test the hypotheses that nighttime suckling and elevated nocturnal prolactin concentrations are essential for the continuation of lactational anovulation, the effects of restricting nursing to twelve h per day (either day or night) on maternal prolactin (Prl) levels and resumption of ovulatory menstrual cycles were studied in five groups of cynomolgus monkeys: Group 1: baby weaned: Group 2: baby fully nursed: Group 3: baby nursed night only; Group 4: baby nursed day only; and Group 5: baby housed with mother but not allowed to nurse. Restrictions were initiated at approximately 150 days postpartum and were achieved by placing a non-nursing jacket over the nursing jacket, which was worn 24 h/day. Fifteen out of seventeen monkeys remained anovulatory while housed with their infants, irrespective of the type of nursing restriction. First postpartum ovulations occurred approximately two months post-weaning. Plasma prolactin concentrations during both day and nighttime were significantly (p < 0.05) greater in the fully nursing group(s) than in all other groups. Fully nursing mothers had significantly (p < 0.01) greater prolactin concentrations at night than during the day. Among the restricted groups, the night only suckling group had significantly greater prolactin concentrations at night than the other restricted groups. There were no differences between daytime values, and within each restricted group there were no significant differences between day and night prolactin levels. We conclude that 1) nighttime suckling is not an absolute prerequisite for sustained lactational anovulation, and 2) suckling-induced hyperprolactinemia is not the principle mediator of lactational anovulation.

Animals↗