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PubMed2006

Amenorrhea: evaluation and treatment.

A thorough history and physical examination as well as laboratory testing can help narrow the differential diagnosis of amenorrhea. In patients with primary amenorrhea, the presence or absence of sexual development should direct the evaluation. Constitutional delay of growth and puberty commonly causes primary amenorrhea in patients with no sexual development. If the patient has normal pubertal development and a uterus, the most common etiology is congenital outflow tract obstruction with a transverse vaginal septum or imperforate hymen. If the patient has abnormal uterine development, müllerian agenesis is the likely cause and a karyotype analysis should confirm that the patient is 46,XX. If a patient has secondary amenorrhea, pregnancy should be ruled out. The treatment of primary and secondary amenorrhea is based on the causative factor. Treatment goals include prevention of complications such as osteoporosis, endometrial hyperplasia, and heart disease; preservation of fertility; and, in primary amenorrhea, progression of normal pubertal development.

Algorithms↗

PubMed1995

Long-term follow-up of women with amenorrhea-galactorrhea treated with bromocriptine.

The present study is aimed at investigating whether long-term use of bromocriptine on patients affected by amenorrhea and galactorrhea may improve the clinical picture after discontinuation of treatment. For this reason 26 patients with amenorrhea and galactorrhea have been studied. Sixteen had high PRL values and 10 were normoprolactinemic. The normoprolactinemic patients underwent a TRH test. All the patients underwent computed skull axial tomography (CT scan) and were treated with bromocriptine, at a daily dosage variable from 2.5 to 10 mg for an average period of 26 months. After discontinuation of treatment, follow-up was carried-out for 20 months. Eighty-seven percent of the patients affected by amenorrhea, galactorrhea and hyperprolactinemia had regular menses, in 75 of the patients galactorrhea completely disappeared. Of the ten patients with normoprolactinemic amenorrhea and galactorrhea, only those who positively responded to the TRH test had regular menstruation and showed disappearance of galactorrhea. Upon discontinuation of treatment amenorrhea recurred in 68% of the cases whereas galactorrhea recurred in 80%. CT scans revealed disappearance of 3 microadenomas and reduction in size of the macroadenoma. Long-term use of bromocriptine represents the first choice treatment for the syndrome of galactorrhea-amenorrhea. In case of relapse, treatment must be continued for an undefined period of time.

Adenoma↗

PubMed1996

[Hypergonadotropic secondary amenorrhea: clinical analysis of 126 cases].

OBJECTIVE: To study the etiology and early diagnosis of hypergonadotropic amenorrhea and to explore the appropriate treatment for preserving their reproductive function. METHODS: 126 cases of secondary amenorrhea with serum follicular stimulating hormone (FSH) levels > or = 40 IU/I, were analysed. Their clinical manifestations, karyotypes, ovarian morphology and histology, reproductive hormone assays, and responses to estrogen therapy and ovulation induction were studied. RESULTS: 6 cases presented with histories of ovarian surgery, radiotherapy or chemotherapy. Among the other 120 cases, 18 manifested amenorrhea before or at 25 years of age, 102 developed amenorrhea after age 25. In the former group, 16 (88.9%) showed unilateral or bilateral gonadal dysgenesis, and the other 2(11.1%) were defined as resistant ovaries. Abnormalities of sex chromosome karyotype occurred in 44.4% (8/ 18). In the latter group, 68 underwent laparotomy or laparoscopy examination. Morphological and histological examinations of both ovaries showed atrophic ovaries in all cases accompanied by 30.9% (21/ 68) unilateral gonadal dysgenesis; sex chromosomal abnormality was found in only one with no sexual immaturation. The efficacy of estrogen treatment was significantly better among cases with amenorrhea less than 1 year as compared with those longer than 1 year. Clomiphene challenge test given to 8 cases during their irregular menstrual stages produced an elevation of FSH levels to > 20 IU/I. without any response of estradiol secretion. CONCLUSIONS: The earlier estrogen therapy is initiated, the greater possibility of pregnancy will be achieved in cases suffering from hypergonadotropic amenorrhea. The clomiphene challenge test may provide evidence of waning ovarian function for early diagnosis.

Adult↗

PubMedDate not supplied

Endocrine causes of amenorrhea.

Amenorrhea is a symptom of a variety of disorders and dysfunctions. It is important for the primary care practitioner to have an understanding of what constitutes normal function and of when to begin a diagnostic assessment of women with amenorrhea. Definitions and the basic principles of menstrual function are reviewed. Causes of amenorrhea are presented, including disorders of the uterus, disorders of the ovary, disorders of the anterior pituitary, and disorders of the central nervous system. The hypothalamic-pituitary-ovarian-uterine axis is used as a framework for the differential diagnosis of amenorrhea. A detailed process for assessing patients with amenorrhea is offered. Components of a amenorrheic-specific history, including menstrual, sexual and contraceptive, life-style, family, and medical histories, are reviewed. A step-by-step laboratory assessment is presented. Management of amenorrhea and health promotion strategies are discussed. The role of primary practitioners caring for amenorrheic women is outlined.

Adolescent↗

PubMed1986

Adult-onset amenorrhea: a study of 262 patients.

A series of 262 patients with amenorrhea of adult onset are reported. Hypothalamic suppression followed by inappropriate positive feedback, and then hyperprolactinemia and ovarian failure are the most frequently encountered etiologies. Other etiologies are diverse and numerically less frequent. Amenorrhea after use of oral contraceptives, or postpill amenorrhea, occurred in 77 (29%) of all patients. The average age of presentation, prior menstrual history, associated morbidity, and subsequent reproductive potential of each diagnostic group are reported. Adult-onset amenorrhea has a less significant impact on future wellbeing than was reported for a similar-sized group of patients whose amenorrhea developed as a result of pubertal aberrancy.

Adult↗

PubMed1991

Is the lactational amenorrhea method a part of natural family planning? Biology and policy.

The lactational amenorrhea method is a natural method of family planning for women who breastfeed their infants. The underlying physiology results in a natural suppression of ovulation, and the concomitant amenorrhea, induced by exclusive (or almost exclusive) breastfeeding. This in addition to the infant's age of 6 months or less and specific feeding pattern are the parameters used to identify the possible return of fertility. The lactational amenorrhea method provides at least 98% protection against pregnancy. Data from a recent multicenter study of breastfeeding support the use of the lactational amenorrhea method as a natural family planning method. The lactational amenorrhea method can be incorporated into natural family planning programs and teaching.

Amenorrhea↗

PubMed1993

Effects of maternal nutritional status and maternal energy supplementation on length of postpartum amenorrhea among Guatemalan women.

To investigate the extent to which better maternal nutrition leads to reduction in length of postpartum amenorrhea, multivariate-logistic and linear-regression analyses were applied to data on 339 mother-infant pairs from the longitudinal Guatemalan Four Village Study, 1969-1977. Maternal triceps skinfold thickness was negatively associated with length of amenorrhea when infant supplementation (a proxy for reduced suckling) was accounted for. However, its effect was small: amenorrhea was only 0.5 mo shorter among women at the 75th percentile than among those at the 25th, equivalent to less than even one additional child during the women's reproductive years. Maternal supplementation was not associated with length of amenorrhea when infant supplementation was controlled. This is in contrast to previous studies in which breast-feeding or infant supplementation was not controlled. These results suggest that infant, not maternal, supplementation influences length of postpartum amenorrhea, and that maternal nutritional status has minimal influence.

Amenorrhea↗

PubMed1996

Prolactin response to suckling and maintenance of postpartum amenorrhea among intensively breastfeeding Nepali women.

The aim of the study was to determine the association between PRL responses to suckling and maintenance of postpartum amenorrhea among breastfeeding mothers. Three blood spot samples (5, 30, and 50 min following a timed nursing bout) were collected from 71 intensively breastfeeding Nepali women for PRL determination. Maternal age, BMI (weight/height2), menstrual status, caste, infant age, nursing bout length, and duration of supplementation were recorded at time of sample collection. Independent and paired t tests, linear regression analyses, and general linear models were used to evaluate differences between cycling (n = 36) and amenorrheic (n = 35) women and associations among variables. Logistic regression analyses were used to relate PRL measures to the odds of maintaining lactational amenorrhea. Amenorrheic breastfeeding mothers had higher (P < .001) PRL levels at all 3 collection times than cycling breastfeeding mothers, and PRL levels declined with time since birth (P < 0.05). The odds (OR) of having ceased lactational amenorrhea was significantly higher (OR = 5.0, 95% Cl = 1.3-19.9) among mothers with lower PRL levels (< or = 10 ng/mL) at 50 min post-sucking, and PRL at 50 min showed a significant dose response relationship with menstrual status. The association between 50 min PRL levels and lactational amenorrhea appears to be independent of time postpartum, maternal age, BMI, nursing bout length, and duration of supplementation. Among intensively nursing women, maintenance of elevated PRL levels across the interbout interval increases the odds of maintaining lactational amenorrhea.

Adult↗

PubMed2004

Frequency of primary amenorrhea due to chromosomal aberration.

OBJECTIVE: To find out the frequency of primary amenorrhea due to chromosomal aberration and the different options available for management. DESIGN: Non-interventional study. PLACE AND DURATION OF STUDY: The study was conducted over a period of two years from April 1999 to March 2001 in Gynaecology and Obstetrics Department, Unit-I, Civil Hospital, Karachi. SUBJECTS AND METHODS: All patients with primary amenorrhea due to chromosomal aberrations were included in study. Patient's detailed history, general physical examination, presence or absence of secondary sexual characteristics, abdominal and pelvic examination finding were noted. Targeted investigations, including ultrasound, hormonal assay, buccal smear and karyotyping, results were recorded. The management options were individually tailored with focus on psychological management. RESULTS: Eighteen patients out of 30,000 patients were diagnosed as having primary amenorrhea. Six had primary amenorrhea due to chromosomal aberrations with the frequency of 0.02%. The age at presentation was 20 years and above in 50%. The most common cause was Turner's syndrome seen in 4 out of 6. The presenting symptoms were delay in onset of menstruation in 05 patients and primary infertility in 01 patient. CONCLUSION: Primary amenorrhea due to chromosomal aberration is an uncommon condition requiring an early and accurate diagnosis. Turner's syndrome is a relatively common cause of this condition. Management should be multidisciplinary and individualized according to the patient's age and symptom at presentation. Psychological management is very important and counselling throughout treatment is recommended.

Adolescent↗

PubMed1995

Gymnasts exhibit higher bone mass than runners despite similar prevalence of amenorrhea and oligomenorrhea.

Female athletes exhibit a higher prevalence of exercise-associated amenorrhea and oligomenorrhea compared with nonathletic women, and both conditions are related to reduced bone mineral density (BMD), particularly at the spine. This study investigated bone mass and oligomenorrhea and amenorrhea in two groups of competitive female athletes with different skeletal loading patterns: gymnasts and runners. Bone mineral density (g/cm2) of the femoral neck, lumbar spine (L2-4), and whole body was assessed by dual energy X-ray absorptiometry (QDR-1000/W, Hologic Inc., Waltham, MA) in collegiate gymnasts (n = 21) and runners (n = 20), and nonathletic college women (n = 19). The runners and gymnasts had similar values for percent body fat (14.7 +/- 2.2% and 15.6 +/- 2.9%, respectively), which were lower (p < 0.001) than controls (22.3 +/- 3.0%). Lean body mass (LBM) did not differ among the groups, but when adjusted for body surface area, gymnasts had a higher LBM/height2 (p = 0.0001) compared with runners and controls. Muscle strength was significantly greater (p < 0.05) in gymnasts for quadriceps, biceps, and hip adductor force, compared with runners and controls. Gymnasts had a significantly later menarche age (16.2 +/- 1.7 years) compared with runners (14.4 +/- 1.7 years) and controls (13.0 +/- 1.2 years). The prevalence of oligo- and amenorrhea was 47% for gymnasts (6 amenorrheic, 4 oligomenorrheic), 30% for runners (3 amenorrheic, 3 oligomenorrheic), and 0% for controls. Furthermore, athletic groups had similar menstrual histories given the higher proportion of gymnasts who had experienced primary amenorrhea. When evaluated since menarche, however, runners had somewhat longer histories due to an earlier age at menarche and slightly older ages. Dietary calcium intake did not differ among groups, although mean values were below the RDA of 1200 mg/day. By athletic group, BMD at any site did not differ among women with amenorrhea versus oligomenorrhea versus eumenorrhea, although there was a trend for the regularly menstruating athletes in both groups to have slightly higher values. Lumbar spine BMD was lower (p = 0.0001) in runners (0.98 +/- 0.11 g/cm2) compared with both gymnasts and controls (1.17 +/- 0.13 and 1.11 +/- 0.11 g/cm2, respectively). Femoral neck BMD differed among all groups (p = 0.0001): gymnasts = 1.09 +/- 0.12 g/cm2 > controls = 0.97 +/- 0.10 g/cm2 > runners = 0.88 +/- 0.11 g/cm2. Whole body BMD was lower (p < 0.01) in runners (1.04 +/- 0.06 g/cm2) compared with gymnasts and controls (1.11 +/- 0.08 and 1.09 +/- 0.06 g/cm2, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Absorptiometry, Photon↗

PubMed2004

Hypergonadotropic amenorrhea and bone density: new approach to an old problem.

Amenorrhea can cause bone loss, but not all mechanisms in this process are known. The degree of bone loss in amenorrheic women is determined by the cause of the amenorrhea. The aim of this study was to investigate the influence of secondary amenorrhea on bone density and to compare the bone density between hypogonadotropic amenorrheic women and hypergonadotropic amenorrheic women. Twenty-two amenorrheic and 12 eumenorrheic women under the age of 40 were involved in this study. Every woman underwent measurements of lumbar spine and femoral neck bone density, body mass index (BMI), and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and prolactin. According to FSH levels, we divided the women with amenorrhea into two groups: hypergonadotropic (n = 7; FSH, >40 IU/l) and hypogonadotropic (n = 15; FSH, < or =40 IU/l) amenorrheic women. Amenorrheic women had a lower lumbar spine bone density than eumenorrheic controls (P = 0.002). Hypergonadotropic amenorrheic women had lower lumbar spine bone density (P = 0.026) than hypogonadotropic ameneorrheic women. In the hypergonadotropic group, only FSH level had a correlation (negative) with lumbar spine bone density (P = 0.05), but in the hypogonadotropic group, there was no correlation between hormonal levels, BMI, age, or duration of amenorrhea. BMI was positively correlated with lumbar spine bone density in amenorrheic women (P < 0.025). Amenorrheic women had lower bone density than eumenorrheic women, but hypergonadotropic amenorrheic women had lower bone density than hypogonadotropic women. The greater bone loss in the hypergonadotropic amenorrheic group could have been caused by a potential direct effect of FSH on bone metabolism.

Age Factors↗

PubMed1984

Pituitary response to insulin-induced hypoglycemia in patients with amenorrhea of different etiologies.

The insulin-induced hypoglycemia test was used to study the hypothalamic-pituitary function of nine normal control subjects and 49 patients with amenorrhea. There were 10 patients with secondary amenorrhea due to hypothalamic dysfunction, eight with hypothalamic failure, eight with primary amenorrhea due to hypogonadotropic hypogonadism, 19 with a prolactin-secreting pituitary adenoma, and four with Sheehan's syndrome. After the administration of insulin (0.15 unit/kg), a significant increase in plasma levels of prolactin, growth hormone, and cortisol occurred in all normal subjects. Of the 10 patients with hypothalamic dysfunction, two had a blunted prolactin response, six had an abnormal growth hormone response, and all had a normal cortisol response. Of those with hypothalamic failure, abnormal responses for prolactin were seen in two patients, for growth hormone in four patients, and all had a normal increase in cortisol. Five of the eight patients with primary amenorrhea had a blunted response for prolactin, six for growth hormone, and there were no abnormalities for plasma cortisol. All 19 patients with pituitary adenomas had a blunted increase in prolactin, 16 had an abnormal growth hormone response, and two had an abnormal cortisol response. Prolactin, growth hormone, and cortisol responses were blunted in all patients with Sheehan's syndrome. These results demonstrate that the release of growth hormone subsequent to insulin-induced hypoglycemia is the most common abnormality seen in women with amenorrhea. The high frequency of abnormal release of prolactin indicates that serum prolactin should be measured when this test is performed. In addition, patients with prolactin-secreting adenomas and those with Sheehan's syndrome should be given an insulin tolerance test before treatment is instituted, so that patients with secondary adrenal insufficiency can be identified.

Amenorrhea↗

PubMed1996

The association between secondary amenorrhea and common eating disordered weight control practices in an adolescent population.

PURPOSE: This study examined the relative importance of low weight, in contrast with other symptoms of eating disorder, as a determinant of amenorrhea. METHODS: A cross-sectional survey was conducted of students at Year 10 (mean age 15.0 years) attending 43 schools in the state of Victoria. Amenorrhea and symptoms of eating disorder were assessed using the Branched Eating Disorders Test, administered through the medium of a notebook computer. RESULTS: The survey response rate was 84% (n = 886). A total of 23% (n = 205) reported either fasting or purging in the previous month. Secondary amenorrhea of at least 3 months duration was reported by 4.1% (n = 35). No statistically significant association was found between amenorrhea and body mass index. In contrast, 40% of amenorrheic subjects reported fasting or purging (P = .03), an association most evident in the heaviest subjects. CONCLUSION: These finding suggests that secondary amenorrhea may develop in normal and above-weight teenagers who engage in eating disordered weight control practices.

Adolescent↗

PubMed2004

Thalidomide-induced amenorrhea: case report and literature review.

OBJECTIVE: To report on a patient with thalidomide-induced amenorrhea and review the literature on the effect of thalidomide on ovarian function. DESIGN: Case report and literature review. SETTING: University medical center. PATIENT(S): A twenty-eight-year-old woman referred for a 2-year history of amenorrhea. INTERVENTION(S): History, physical examination, laboratory evaluation of the patient, and subsequent medical therapy. Literature review performed by using OVID/Medline and PubMed search strategies. MAIN OUTCOME MEASURE(S): Diagnosis and appropriate management of thalidomide-induced amenorrhea. RESULT(S): Elevated pituitary gonadotropins, other labs normal. All known causes of hypergonadotropic amenorrhea were excluded. CONCLUSION(S): Thalidomide induces hypergonadotropic amenorrhea. Although this effect appears to be reversible, the long-term effect of thalidomide on ovarian reserve is unclear.

Adult↗

PubMed2001

A longitudinal study of disturbances of the hypothalamic-pituitary-adrenal axis in women with progestin-negative functional hypothalamic amenorrhea.

OBJECTIVE: To longitudinally evaluate disturbances of the hypothalamic-pituitary-adrenal (HPA) axis in women with secondary progestin-negative hypothalamic amenorrhea. DESIGN: Retrospective cohort study. SETTING: Yokohama City University, Yokohama, Japan. PATIENT(S): Twenty-four women with progestin-negative hypothalamic amenorrhea. INTERVENTION(S): Administration of human corticotropin-releasing hormone (hCRH) and treatment with a combination of estrogen and progesterone. MAIN OUTCOME MEASURE(S): Plasma cortisol and ACTH concentrations and period required for recovery from amenorrhea. RESULT(S): Plasma ACTH concentrations 30 and 60 minutes after injection of hCRH and the percent maximum increment (%Cmax) of ACTH were significantly lower in the amenorrheic patients compared with the control group patients. The basal cortisol was significantly higher, and the %Cmax of cortisol was significantly lower. In the 16 patients who recovered from amenorrhea, there was a significant positive correlation (Y = 1.93X-10.8, r = 0.629) between the basal cortisol concentrations (X) and the period for recovery (Y). The serum E2 gradually increased before recovery, and this E2 increase was preceded by changes in the plasma cortisol concentration and the %Cmax values of cortisol and ACTH. CONCLUSION(S): The CRH test might be useful for evaluating the roles of stress and for estimating the period required for recovery in hypothalamic amenorrhea.

Adrenocorticotropic Hormone↗

PubMed2002

Diagnostic role of inhibin B in resistant ovary syndrome associated with secondary amenorrhea.

To report two rare cases of gonadotropin-resistant ovary syndrome associated with secondary amenorrhea and normal levels of inhibin B. Case report. Two university teaching hospitals. Two women presenting with secondary amenorrhea and infertility. The control group for the inhibin B levels consisted of 30 cycling women of reproductive age. Medical history, physical examination, laboratory data, histologic findings, and IVF results. Diagnosis and treatment of resistant ovary syndrome. Case 1 was a 25-year-old woman with secondary amenorrhea and primary infertility. She had high serum levels of FSH and LH, low E(2) levels, and normal inhibin B levels (62 pg/mL). Karyotype was 46,XX, and ovarian biopsy showed primordial follicles with oocytes. Administration of GnRH analogue with hMG for 15 days did not affect E(2) levels. She had a successful pregnancy with IVF using donor oocytes. Case 2 was a 24-year-old woman with secondary amenorrhea. She had elevated serum levels of FSH and LH, low E(2) levels, and normal inhibin B levels (57 pg/mL). Karyotype was 46,XX and ovarian biopsy showed primordial follicles. Administration of GnRH analogue with hMG for 12 days did not affect E(2) levels. Both women were given estrogen-progestin replacement therapy. Inhibin B has a diagnostic role in women with gonadotropin-resistant ovary syndrome associated with secondary amenorrhea. A review of the literature confirms the uniqueness of the diagnostic role of inhibin B in these cases.

Adult↗

PubMed1992

Pulsatile luteinizing hormone secretion in hypothalamic amenorrhea, anorexia nervosa, and polycystic ovarian disease during naltrexone treatment.

OBJECTIVE: To determine if chronic treatment with the long-acting oral opioid antagonist naltrexone can increase luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion in women with secondary amenorrhea. DESIGN: Prospective. SETTING: Large reproductive endocrinology unit of an academic hospital. PATIENTS: Three groups of women with oligomenorrhea or amenorrhea: (1) hypothalamic amenorrhea; (2) anorexia nervosa; and (3) polycystic ovarian disease (PCOD). INTERVENTION: Naltrexone 50 mg every day for 4 days. MAIN OUTCOME MEASURES: Luteinizing hormone pulse pattern, frequency and amplitude, mean LH and FSH levels, measured by serial blood sampling over a 6-hour period before and after naltrexone. RESULTS: Naltrexone caused a significant increase (P less than 0.05) of the LH pulse frequency in patients with hypothalamic amenorrhea and in PCOD but not in anorexia nervosa. The mean levels of LH and FSH and LH pulse amplitudes were not significantly changed by naltrexone. The naltrexone nonresponders were underweight either because of simple weight loss or anorexia nervosa and had low levels of estradiol and an LH pulse pattern similar to the luteal one. CONCLUSION: The luteal LH pulse pattern in weight loss-related amenorrhea is caused by a nonopioid, undernutrition-linked factor.

Activity Cycles↗

PubMed1997

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↗