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Stressful life events and affective disorders inhibit pulsatile LH secretion in hypothalamic amenorrhea.

The aim of this study was to evaluate relationships between emotional state and hypothalamic activity in patients with hypothalamic secondary amenorrhea. Sixty-seven normal weight patients with hypothalamic amenorrhea were submitted to concomitant psychological and LH pulsatility evaluation. Structured clinical interview for anxiety and depressive disorders (DSM III-R) as well as life events investigations (Paykel test) were performed. LH pulses (blood sampling every 10 min for 4 hr) were analyzed through DETECT program and Instantaneous Secretory Rate were computed. Twenty-one patients reporting life events associated to the onset of amenorrhea had LH pulse frequency (2.28 +/- 1.10 pulses/4 hr) lower than those without life events (3.40 +/- 1.46 p = .007). LH pulses amplitude was lower in patients meeting a DSM III-R (21 cases: 1.22 +/- 0.96 mIU/ml) diagnosis than in those without (1.99 +/- 1.20 p = .04) diagnosis. Plasma estradiol and FSH levels as well as duration of amenorrhea and Body Mass Index were similar among groups. It is concluded that psychogenic factors (namely the presence of life events related to the onset of menstrual disorder) are associated with significant and specific changes of hypothalamic activity which could be involved in determining hypogonadism.

Adult↗

The natural family planning--lactational amenorrhea method interface: observations from a prospective study of breastfeeding users of natural family planning.

Methods of natural family planning are sometimes difficult for women to use during lactation. When this is so, the lactational amenorrhea method may prove useful. Researchers agree that a fully breastfeeding woman who is amenorrheic is 98% protected from pregnancy for up to 6 months after delivery. The fertility status of 74 users of natural family planning during the time they would have been protected by the lactational amenorrhea method is examined. Underlying hormonal profiles show that there was little ovarian activity during this time. Eight ovulatory events occurred during the period of protection by the lactational amenorrhea method, of which four fulfilled minimum criteria for adequacy; there were no pregnancies during this period. However, some women did report experiencing fertile mucus symptoms during this time that were often unrelated to estrogen production. Using the lactational amenorrhea method rather than natural family planning allows them to avoid unnecessary abstinence.

Amenorrhea↗

Psychological correlates of functional hypothalamic amenorrhea.

OBJECTIVE: To determine whether mood, attitudes, or symptoms of disordered eating discriminated women with functional hypothalamic amenorrhea (FHA) from those with organic causes of amenorrhea and eumenorrhea. DESIGN: Cross-sectional comparison of women with FHA, women with organic amenorrhea, and eumenorrheic control women. SETTING: Clinical research center in an academic medical institution. PATIENT(S): Seventy-seven women > or =18 years old with time since menarche > or =5 and < or =25 years were recruited by advertisement. INTERVENTION(S): Ovulation was confirmed in eumenorrheic control women. Causes of anovulation were carefully documented in amenorrheic participants and LH pulse profiles were obtained to document the diagnosis of FHA. All participants were interviewed and completed questionnaires. MAIN OUTCOME MEASURE(S): Self-report measures of dysfunctional attitudes, coping styles, and symptoms of depression and eating disorders. RESULT(S): Women with FHA reported more depressive symptoms and dysfunctional attitudes than did eumenorrheic women, but not significantly more than women with organic amenorrhea. However, women with FHA reported significantly more symptoms of disordered eating than did either anovulatory or ovulatory women. CONCLUSION(S): The findings are consistent with the hypothesis that FHA is precipitated by a combination of psychosocial stressors and metabolic challenge.

Adaptation, Psychological↗

Amenorrhea following the use of oral contraceptives.

Clinical aspects and the incidence of the various underlying etiologic factors were studied in 86 patients with post-oral contraceptive amenorrhea. Patients were divided into two groups according to the presence or absence of detectable galactorrhea. Group I was composed of 55 amenorrheic patients without detectable galactorrhea and group II included 31 patients with amenorrhea associated with galactorrhea. Both groups were comparable for age, gravidity, duration of intake of oral contraceptives, and duration of amenorrhea. The incidence of previous oligomenorrhea and late menarche was high in both groups. The most striking difference between the two groups was in the incidence of pituitary prolactin-secreting tumor--32% among patients with galactorrhea and less than 2% among patients without galactorrhea. Identification of galactorrhea and accurate diagnosis of its causes are mandatory for successful management of postpill amenorrhea.

Adolescent↗

Plasma luteinizing hormone-releasing hormone levels in normal women and patients with amenorrhea.

Plasma levels of immunoreactive luteinizing hormone-releasing hormone (LH-RH) in 89 women with normal menstrual cycles and 109 patients with amenorrhea of various etiologies were determined by specific radioimmunoassay after methanol extraction. The LH-RH levels in patients with hypergonadotropism and Sheehan's syndrome were more than 10 pg/ml, and were significantly higher than basal levels during normal cycles (4.2 +/- 0.3 pg/ml). The mean levels of LH-RH were low in all hypogonadotropic patients with amenorrhea, with the exception of a few patients who showed high LH-RH levels suggestive of a pituitary lesion. The LH-RH levels in patients with polycystic ovary syndrome were comparable with basal levels during normal cycles. It is concluded that, although there is considerable overlap of the plasma LH-RH levels in each group of amenorrheic patients divided according to gonadotropin level, determination of LH-RH levels may be useful for the differentiation of hypothalamic amenorrhea from pituitary amenorrhea.

Adolescent↗

Evidence of luteinizing hormone secretion in hypothalamic amenorrhea associated with weight loss.

The lack of plasma luteinizing hormone (LH) pulsatile pattern or episodic LH secretory bursts during night have been demonstrated in hypothalamic amenorrhea. The availability of both sensitive and specific immunofluorimetric assay and algorithm for pulse detection enabled us to reanalyze the question of whether or not patients with hypothalamic amenorrhea secrete LH in a pulsatile fashion. Seven women with secondary amenorrhea associated with weight loss and four normally cycling women were studied, sampling every 5 minutes for 8 hours. Control subjects were studied during four different phases of the menstrual cycle. In all amenorrheic patients, a frequent LH pulsatile secretion, with pulses of low amplitude, was found (10.7 +/- 1.4 peaks/8 h; mean +/- SEM). The pulse frequency was significantly higher (P less than 0.05) than any phases of the control group (early follicular: 7 +/- 0.4 peaks/8 h; late follicular: 6.8 +/- 0.6 peaks/8 h; early luteal: 4.3 +/- 0.4 peaks/8 h; late luteal: 7 +/- 0.3 peaks/8 h). The LH pulsatile release in amenorrheic patients showed a mean pulse duration and amplitude shorter than in any phase of the menstrual cycle of the controls. In conclusion, in weight-loss-related-amenorrhea, the major change was not the absence of the LH pulsatile release but its increased frequency with reduced pulse amplitude.

Adolescent↗

The World Health Organization Multinational Study of Breast-feeding and Lactational Amenorrhea. I. Description of infant feeding patterns and of the return of menses. World Health Organization Task Force on Methods for the Natural Regulation of Fertility.

OBJECTIVE: To detect differences between populations in both infant feeding practices and the duration of lactational amenorrhea, if they exist. DESIGN: Prospective, nonexperimental, longitudinal follow-up study. SETTING: Five developing and two developed countries. PATIENT(S): Four thousand one hundred eighteen breast-feeding mothers and their infants. INTERVENTION(S): Breast-feeding women collected ongoing information about infant feeding and family planning practices, plus the return of menses. Fortnightly follow-up occurred in the women's homes. MAIN OUTCOME MEASURE(S): Breast-feeding frequency by day (and by night); 24-hour breast-feeding duration, percent of all infant feedings that were milk/milk-based (and solid/semisolid foods); time until the end of full breast-feeding; time until regular supplementation; and time until the end of lactational amenorrhea. RESULT(S): Differences between the centers in the duration of amenorrhea were substantial, ranging from a median of 4 months in New Delhi (India) to 9 months in Chengdu (China). Women in developed countries (but also women in Chengdu) were more likely to delay supplementation (for up to 5 months), whereas women in Santiago (Chile), Guatemala City (Guatemala), and Sagamu (Nigeria) started supplements much earlier, sometimes as early as 1 week after birth. CONCLUSION(S): Both breast-feeding behavior and the duration of lactational amenorrhea vary markedly across settings, indicating that breast-feeding promotion and family planning advice should be site- and culture-specific.

Adult↗

Adolescent secondary amenorrhea: association with hypothalamic hypothyroidism.

In adolescent girls, secondary amenorrhea can result from a variety of physiologic and psychologic disturbances. Previous reports associating amenorrhea and primary hypothyroidism have not distinguished between the alternative etiologic roles of thyroxine deficiency and hyperprolactinemia. We have evaluated two girls with secondary amenorrhea who had clinical and chemical evidence of hypothyroidism. Both had low basal T4 values (0.8 and 3.2 microgram/dl), calculated free T4 (0.1 and 0.7 ng/dl), and T3 (51 and 81 ng/dl). Both had undetectable basal TSH with normal TSH response to TRH. Basal FSH and LH values were normal, as was the response to LHRH. Basal prolactin levels were 6 and 14 ng/ml, respectively, and both girls had growth hormone responses of greater than or equal to 15 ng/ml in response to insulin-induced hypoglycemia. Pituitary-adrenal function and reserve were also normal. In neither patient was there any historical, physical, or laboratory features compatible with anorexia nervosa. After treatment with 1-thyroxine, both girls had a resumption in menses. These two adolescent girls thus appear to have isolated hypothalamic hypothyroidism. The associated secondary amenorrhea demonstrates that thyroid deficiency alone, without hyperprolactinemia, can interfere with normal hypothalamic-pituitary-ovarian function.

Adolescent↗

Anorexia nervosa, athletics, and amenorrhea.

Menstrual dysfunction is common in adolescents who are involved in intensive athletic activity or who are limiting their nutritional intake excessively. The mechanism for hypothalamic amenorrhea in athletes and dieters is not yet fully understood. Other causes of menstrual dysfunction due to pregnancy, central lesions, hormone imbalance, or ovarian failure should be excluded in the athlete with amenorrhea. Amenorrheic patients who have sufficient estrogen effect on their endometrium to have withdrawal bleeding following exposure to progestins should be cycled with progestins on a regular basis to prevent endometrial hyperplasia. Estrogen replacement with cyclic progestin should be considered in the hypoestrogenic adolescent with prolonged amenorrhea. The long-term consequences of hypothalamic amenorrhea in adolescents remain to be determined.

Adolescent↗

Amenorrhea, osteopenia, and the female athlete.

Athletic amenorrhea is a problem because it is associated with an increased risk of injuries and potentially an increased risk of osteoporosis in later life. This article gives suggestions for the evaluation of the athlete with amenorrhea and for treatment protocols. Primary care physicians should routinely screen female adolescent athletes for amenorrhea and, if athletic amenorrhea is present, initiate treatment or referral for treatment for this important problem with short- and long-term complications.

Adolescent↗

Pharmacologic management of athletic amenorrhea.

Amenorrhea is the absence of menses in reproductive-age women. The female athlete can frequently experience amenorrhea during athletic training. This article serves as an overview of the possible causes of amenorrhea. Its primary role, however, is to focus on both nonpharmacologic and pharmacologic treatment options for the female with athletic amenorrhea.

Adolescent↗

Results of cytogenetic investigation in adolescent patients with primary or secondary amenorrhea.

A cytogenetic study of 77 adolescent girls with primary or secondary amenorrhea was performed. A pathologic or male karyotype was found in 18 (26.4%) of 68 patients with primary amenorrhea. In 1 (11.1%) of 9 patients with secondary amenorrhea, 46,XX/47,XXX mosaicism was recovered. The importance of the cytogenetic investigations in patients with primary or secondary amenorrhea was discussed.

Adolescent↗

Variation in endometrial thickening in women with amenorrhea on tamoxifen.

Tamoxifen is reported to increase the risk of endometrial cancers mostly in postmenopausal women. In the Royal Marsden chemoprevention programme, we noted that premenopausal women at the start of tamoxifen/placebo who developed amenorrhea may be at special risk of endometrial cancer. The aim of this report was to investigate recently amenorrheic women by measuring plasma estradiol (E2), follicular stimulating hormone (FSH), and endometrial thickness (ET) by transvaginal ultrasound (TVUS). ET readings and E2 levels were available in the same proportion of women on tamoxifen or placebo. Women on placebo developed amenorrhea with upper limit of E2 readings of 450 pmol/L. In both postmenopausal women and recently amenorrheic women with low E2 (< or = 450 pmol/L), tamoxifen significantly increased endometrial thickening (p < 0.0001 and < 0.005 respectively). Conversely, tamoxifen did not result in endometrial thickening in women with high E2 (> 450 pmol/L), with a trend to lower ET readings (p = 0.07). Finally, all five women who developed endometrial cancer were premenopausal at the start of tamoxifen/placebo. Two of these five women were asymptomatic with increased ET readings (17 mm and 17 mm) and low E2 levels (32 and 51 pmol/L). These results indicate that women who develop amenorrhea on tamoxifen may be at special risk of endometrial cancer. Tamoxifen causes endometrial thickening in amenorrheic women with low E2 but has an opposite antiestrogenic effect in women with high E2. We recommend that women who develop amenorrhea on tamoxifen especially in the presence of endometrial thickening, low E2 levels, and/or gynaecological symptoms warrant further investigations.

Amenorrhea↗

[Rational hormonal diagnosis of secondary amenorrhea].

The usefulness of the guideline recommended in 1976 by the World Health Organization (WHO) for the differential diagnosis of ovarian sterility needs critical reevaluation, since it does not take into account new aspects such as the pulsatility of GnRH secretion, androgen excess, or thyroid disorders and other phenomena related to ovarian dysfunction. In order to demonstrate the relative frequency of such phenomena, the authors examined 183 women with secondary amenorrhea of more than three months' duration (mean +/- SD = 12.7 +/- 18.4 months). The endocrine status of these women was examined under standardized conditions in two clinical endocrinology units in the cities of Hamburg and Berlin. The percentages of abnormal hormonal data (greater than mean +/- SD + gray zone) were as follows: testosterone (T) 39.9%; DHEA sulfate (DS) 29.5%; prolactin (PRL) 18.0%; TSH 11.5%; FSH or LH 26.8%; estradiol (E2) 30.1%. Among 96 patients with increased T and/or DS (52.5% of all patients), 53 patients (55.2%) did not show any clinical signs of androgenization (hirsutism, acne). Retrospective evaluation of all data revealed that a stepwise diagnostic procedure would have resulted in the following cumulative percentages of hormonal abnormalities: (1) T = 39.9%; (2) +DS = 52.5%; (3) +PRL = 60.2%; (4) +LH/FSH = 82.0%; (5) +E2 = 91.2%; (6) +TSH = 92.3%. Only in 7.7% of all patients were all hormonal parameters within normal ranges. Individual case analysis showed that 52.5% of all patients had hyperandrogenemia, while 18% had hypothalamic amenorrhea without any other pathologic condition; 17.5% had hyperprolactinemia and 3.3% primary ovarian insufficiency. Another 4.9% had hypothyroidism only, while 1.1% had exclusively hyperthyroidism. Combined hormonal deviations were found in 24% of all patients. Considering the differential diagnosis of secondary amenorrhea from an economic point of view, one comes to the conclusion that direct and indirect expenditures are similar in magnitude, no matter whether one prefers a conventional stepwise procedure or a one-step hormonal analysis encompassing all potentially relevant hormones (DM 859.00 + 10 weeks waiting time vs. DM 827.50 + 1 week waiting time). Androgen excess is much more frequent than was believed; hirsutism and/or acne by no means necessarily occur in cases of androgen excess. Hyperprolactinemia is less frequent than hyperandrogenemia. Thyroid status should be evaluated in all women with functional amenorrhea. The stepwise diagnostic procedure as recommended by the WHO is time-consuming, complicated, and sometimes incomplete in the diagnostic work-up, with obvious potential disadvantages for therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Scoliosis and fractures in young ballet dancers. Relation to delayed menarche and secondary amenorrhea.

In a survey of 75 dancers (mean age, 24.3 years) in four professional ballet companies, we found that the prevalence of scoliosis was 24 percent and that it rose with increases in age at menarche. Fifteen of 18 dancers (83 percent) with scoliosis had had a delayed menarche (14 years or older), as compared with 31 of 57 dancers (54 percent) without scoliosis (P less than 0.04). The dancers with scoliosis had a slightly higher prevalence of secondary amenorrhea (44 percent vs. 31 percent), the mean (+/- SD) duration of their amenorrhea was longer (11.4 +/- 18.3 vs. 4.1 +/- 7.4 months; P less than 0.05), and they scored higher on a questionnaire that assessed anorectic behavior. The incidence of fractures was 61 percent (46 of 75 dancers), and it rose with increasing age at menarche. Sixty-nine percent of the fractures that were described were stress fractures (mostly in the metatarsals), and their occurrence had an even stronger correlation with increased age at menarche. The incidence of secondary amenorrhea was twice as high among the dancers with stress fractures (P less than 0.01), and its duration was longer (P less than 0.05). In 7 of 10 dancers in whom endocrine studies were performed, the amenorrheic intervals were marked by prolonged hypoestrogenism. These data suggest that a delay in menarche and prolonged intervals of amenorrhea that reflect prolonged hypoestrogenism may predispose ballet dancers to scoliosis and stress fractures.

Adolescent↗

A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group.

BACKGROUND: Cabergoline is a long-acting dopamine-agonist drug that suppresses prolactin secretion and restores gonadal function in women with hyperprolactinemic amenorrhea. We designed a study to compare its safety and efficacy with those of bromocriptine, which has been the standard therapy. METHODS: A total of 459 women with hyperprolactinemic amenorrhea were treated with either cabergoline (0.5 to 1.0 mg twice weekly) or bromocriptine (2.5 to 5.0 mg twice daily), administered in a double-blind fashion for 8 weeks and subsequently in an open fashion for 16 weeks, during which adjustments in the dose were made according to the response. Of the 459 women, 279 had microprolactinomas, 3 had macroprolactinomas, 1 had a craniopharyngioma, 167 had idiopathic hyperprolactinemia, and the remainder had an empty sella. Clinical and biochemical status was assessed at 2-week intervals for 8 weeks and monthly thereafter for a total of 6 months, with an additional assessment at 14 weeks. RESULTS: Stable normoprolactinemia was achieved in 186 of the 223 women treated with cabergoline (83 percent) and 138 of the 236 women treated with bromocriptine (59 percent, P < 0.001). Seventy-two percent of the women treated with cabergoline and 52 percent of those treated with bromocriptine had ovulatory cycles or became pregnant during treatment (P < 0.001). Amenorrhea persisted in 7 percent of the cabergoline-treated women and 16 percent of the bromocriptine-treated women. Adverse effects were recorded in 68 percent of the women taking cabergoline and 78 percent of those taking bromocriptine (P = 0.03); 3 percent discontinued taking cabergoline, and 12 percent stopped taking bromocriptine (P < 0.001) because of drug intolerance. Gastrointestinal symptoms were significantly less frequent, less severe, and shorter-lived in the women treated with cabergoline. CONCLUSIONS: Cabergoline is more effective and better tolerated than bromocriptine in women with hyperprolactinemic amenorrhea.

Adolescent↗

Amenorrhea in ballet dancers in the Netherlands.

The prevalence of amenorrhea was studied among 113 professional and student ballet dancers in the Netherlands (mean age 23.3 yr, SD 4.8). Sixty-one dancers not on oral contraceptives were included in the subsequent analyses. Six cases (prevalence 9.8 percent, 95 percent confidence interval: 2.4-17.2) with secondary amenorrhea (< or = 4 cycles per year; previous menstruation > or = 3 months prior to the study; menarche > or = 1 yr prior to the study) were found. Two dancers had primary amenorrhea (no menarche at the age of > or = 16). There was a negative correlation between the age of menarche and the number of menstrual cycles during the 12 months preceding the study (r = -0.46, P = 0.001). Body composition (four-compartment model), amount of dancing (recorded), resting energy expenditure (ventilated hood), dietary intake (recorded), and indices of eating disorders (Eating Disorders Inventory, EDI) were studied in 15 of the dancers, 5 amenorrheic and 10 eumenorrheic. No significant differences were found between the amenorrheic and eumenorrheic dancers. An explanation for the lower prevalence of amenorrhea in ballet dancers in the Netherlands, compared with U.S. dancers, was not obvious. Relatively low EDI scores (25.8, SD 14.5) in a subsample of 24 dancers could indicate less rigid emphasis on leanness and dieting.

Adult↗