Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002453 (amenorrhea)
 6,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sensitive in vitro assay based on the stimulation of estrogen production by cultured rat granulosa cells was recently developed for the measurement of biologically active FSH. This bioassay system is specific for FSH, highly sensitive, and capable of measuring basal FSH levels in rat serum. The granulosa cell aromatase bioassay was improved by the use of additives known to enhance FSH activity and by pretreatment of serum with 12% polyethylene glycol to remove inhibitory substances. We applied this method to the measurement of bioactive FSH levels in serum samples from human subjects. As determined in daily blood samples during ovulatory menstrual cycles in seven women, bioactive FSH levels exhibited a pattern closely resembling that of immunoreactive FSH. The mean bioactive serum FSH levels were 29.9, 20.5, 39.2, and 14.8 mIU/ml for the early follicular phase, late follicular phase, preovulatory surge, and luteal phase, respectively. The bio- to immunoratio (B:I) throughout the menstrual cycle ranged from 1.4-3.4, with a mean of 2.5. The ratios for early follicular phase, late follicular phase, preovulatory surge, and luteal phase were 2.7, 2.3, 1.4, and 2.6, respectively. The correlation coefficient (r) of the serum FSH values obtained by bioassay and RIA was 0.91. FSH bioactivity was also measured in patients in each of the following categories with the following mean values: oral contraceptive pill users (undetectable), hypothalamic amenorrhea (18.7 mIU/ml; B:I, 2.6), premature ovarian failure (163 mIU/ml; B:I, 1.7), and postmenopausal women (191 mIU/ml; B:I, 1.6). These findings suggest that measurement of immunoreactive FSH levels correctly reflects the biological activity of FSH in serum of cycling women and patients in certain hyper- and hypogonadotropic states. The granulosa cell aromatase bioassay represents a new tool for future assessments of biologically active FSH in physiological and pathophysiological conditions.
 ...
PMID:Serum bioactive follicle-stimulating hormone during the human menstrual cycle and in hyper- and hypogonadotropic states: application of a sensitive granulosa cell aromatase bioassay. 308 37

A sensitive and specific in vitro granulosa cell aromatase bioassay was adapted to measure bioactive FSH (bio-FSH) levels in urine samples. Urinary levels of bio-FSH, immunoreactive LH, estrone conjugates, and pregnanediol-3-glucuronide (PdG) were measured in first morning urine samples during the menstrual cycle in six cycling women and four lowland gorillas. The cycle length of women was relatively constant [28 +/- 1 (+/- SD) days], but varied from 28-38 days for lowland gorillas; the length of the luteal phases was relatively constant for both. All subjects had a midcycle LH peak and a luteal phase elevation in PdG. In addition, urinary estrogen excretion displayed a midcycle elevation that preceded the LH peak and a luteal phase increase similar to that of PdG. The bio-FSH levels in urine of cycling women, although at almost 100-fold higher concentrations, exhibited a pattern that closely resembled that of serum bio-FSH levels reported earlier, with an early follicular phase rise and a midcycle peak. Statistical analysis indicated a highly significant correlation (r = 0.90) between serum and urinary bio-FSH levels during the human menstrual cycle and in women in several hypo- and hypergonadotropic states, including oral contraceptive pill users, hypothalamic amenorrhea, premature ovarian failure, and postmenopause. Although a midcycle bio-FSH surge was also detected in lowland gorillas, two peaks of bio-FSH levels were consistently found during the follicular phase. The late follicular phase increase in bio-FSH levels was presumably involved in follicle selection and preceded the midcycle FSH peak by about 6 days, whereas the timing of the early follicular phase peak was variable, suggesting the involvement of complex regulatory mechanisms. These findings suggest that measurement of urinary bio-FSH levels in humans reflects serum bio-FSH in subjects in several physiological and pathological states. Studies of urinary bio-FSH levels in humans and nonhuman primates are useful in monitoring menstrual cycles, and the gorillas may be a model for understanding human reproductive cycles. The urinary granulosa cell aromatase bioassay should be useful for future assessment of bio-FSH levels in situations where serum measurements are impractical or in animal species for which specific FSH RIAs are not available.
 ...
PMID:Monitoring the menstrual cycle of humans and lowland gorillas based on urinary profiles of bioactive follicle-stimulating hormone and steroid metabolites. 310 37

Women with Wilson's disease may have severe oligomenorrhea or amenorrhea whose cause is unknown. The endocrine profile of four such cases was investigated by measuring basal values and the response to dynamic tests of hypothalamic, pituitary, thyroid, and adrenal function, which all proved normal. Ovarian function was disturbed, as witnessed by low estradiol, high total testosterone (T) levels with normal free T, and mildly elevated androstenedione. An interference of ovarian follicular aromatase activity possibly due to copper intoxication could explain these findings as the cause of the ovulatory disturbances of Wilson's disease.
 ...
PMID:Endocrine studies of the ovulatory disturbances in Wilson's disease (hepatolenticular degeneration). 381 73

The present study was designed for exploration of hormonal disturbances underlying common forms of amenorrhea. Polycystic ovary syndrome (PCO) patients and obese amenorrheic subjects had significantly elevated estrone (E1) levels, elevated luteinizing hormone/follicle-stimulating hormone ratios, and an exaggerated luteinizing hormone response to luteinizing hormone-releasing hormone. However, androstenedione (delta 4A), the precursor of E1, was elevated only in PCO. Thus, the E1/delta 4A ratio, which provides an indirect index of aromatase activity in extraglandular sites, was raised in obese subjects as a group but not in PCO subjects. These findings suggest that elevated E1 levels, which give rise to abnormal gonadotropin secretion, arise from increased available androgens in PCO but from an increased effect of aromatase (present in adipose tissue) in obese subjects. Measurement of androgens and the E1/delta 4A ratio provides insights into the relative contributions of hyperandrogenemia and enhanced aromatase activity to the genesis of amenorrhea in these groups. In patients with suppressed estradiol levels associated with hyperprolactinemia or weight loss, follicle-stimulating hormone levels were suppressed, while luteinizing hormone was not elevated. Prolactin excess explains these findings in hyperprolactinemia. Plasma E1 levels and the E1/delta 4A ratio were suppressed in patients with weight loss, possibly as a consequence of reduced adiposity. This finding suggests that hypothesis that a minimum level of E1, dependent upon adequate adiposity, is critical for the normal mature function of the hypothalamic-pituitary-ovarian axis. Abnormal E1/delta 4A ratios, high in obesity-associated amenorrhea and suppressed in weight loss-associated amenorrhea, may provide specific markers for these groups of patients.
 ...
PMID:Altered androstenedione and estrone dynamics associated with abnormal hormonal profiles in amenorrheic subjects with weight loss or obesity. 388 79

This study was undertaken to contrast the hormonal profiles in patients with various hyperandrogenemic states in an attempt to correlate clinical manifestations with specific hormonal abnormalities. Patients with idiopathic hirsutism, polycystic ovaries, and a syndrome recently described by us, amenorrhea with cryptic hyperandrogenemia, ie, without hirsutism, participated. Total testosterone, the testosterone: sex-hormone-binding globulin (SHBG) ratio, and androstenedione levels were elevated in each group of patients. SHBG levels were suppressed in patients with idiopathic hirsutism and in patients with polycystic ovaries. In patients with polycystic ovaries or cryptic hyperandrogenemia, plasma estrone levels were elevated and the luteinizing hormone (LH) responses to luteinizing-hormone-releasing hormone (LH-RH) were exaggerated. Estrone is derived from androstenedione under the influence of the enzyme, aromatase. While elevated androstenedione occurred in both patients with polycystic ovaries or idiopathic hirsutism, estrone levels were only elevated in patients with polycystic ovaries. Reduced aromatase activity may have protected patients with idiopathic hirsutism from elevated estrone values and, thereby, from menstrual disturbances. The hormonal profiles in polycystic ovary syndrome and in patients with amenorrhea with cryptic hyperandrogenemia were very similar, with the exception that SHBG levels were high normal in three of five patients with cryptic hyperandrogenemia while estrone values were markedly elevated in these patients. Elevated estrone levels may explain the normal SHBG values, which are usually suppressed in hyperandrogenemic states. While each of the hyperandrogenemic disorders studied has a characteristic hormonal profile, the various clinical manifestations cannot be accounted for solely by abnormalities in circulating hormonal levels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Variable clinical and hormonal manifestations of hyperandrogenemia. 674 43

Polycystic ovarian syndrome (PCO) is a relatively poorly defined type of steroidogenic abnormality, dependent on an overproduction of lutropin (LH). The PCO is characterized by infertility, amenorrhea or oligomenorrhea, obesity and hirsutism. The clinical symptoms are associated with typical morphological changes of the ovaries. It has been suggested that hyperplastic secondary interstitial cells and theca cells are the main site of excess androgen production. In PCO the elevation of androgens is observed, while the estrogen level is normal or slightly decreased. In the ovarian sex steroidogenic pathways, 17 alpha-hydroxylase, which produces androgens and aromatase, which converts androgens to estrogens are important regulatory enzymes. Major components of 17 alpha-hydroxylase and aromatase are cytochromes P450 17 alpha and P450 arom. Histochemical investigations revealed increased immunoreactivity with the antibody directed against P450 17 alpha in theca cells. In this review data from literature are presented and discussed regarding endocrinological and molecular background of PCO.
 ...
PMID:[Molecular basis of polycystic ovarian syndrome]. 868 42

Aromatase inhibitors (AI) block the last enzymatic step of estrogen production, the aromatization of the A-cycle of aromatizable androgens and particularly, androstenedione (D4) and testosterone (T). Molecules designed for interfering with aromatase activity have existed for many years. Yet the activity of products of the aminogluthetimide era was too unspecific and these substances carried too many side effects for being used clinically. Today, however, 3rd generation AIs have become available that are highly specific and essentially devoid of side effects. These molecules have recently been approved for treating breast cancer in post-menopausal women, either in advanced forms, or as part of adjuvant therapy. In women whose ovaries are active, a temporary inhibition of E2 production will activate gonadotropins and in turn, stimulate follicular growth. In cancer patients, this property precludes the use of AIs in women whose ovaries are still active, unless gonadotropins are blocked. In infertile patients, this property of AIs has been put to play for inducing ovulation. AIs have been used both in women who do not ovulate but whose hypothalamo-pituitary-gonadal (HPG) axis is active (oligo-anovulators of PCOD type) and in those who ovulate regularly but in whom multiple ovulation is sought for treating infertility or as part of IVF. Like CC, AIs are not usable in women whose gonadotropins are suppressed, as in the case of hypothalamic amenorrhea. The sum of data available on the use of AI for inducing ovulation remains however meager to this date and is mainly constituted of pilot and non-randomized trials. Yet mounting evidence tends to support AIs' advantages over CC for induction of ovulation. Hence, we think that these drugs will play a key role for the induction of ovulation in the future.
 ...
PMID:[Use of aromatase inhibitors in infertile women]. 1614 May 57

Aromatase inhibitors (AI) block the last enzymatic step of estrogen production, the aromatization of the A-cycle of aromatizable androgens and particularly, androstenedione (delta4) and testosterone (T). Molecules designed for interfering with aromatase activity have existed for many years. Yet the activity of products of the aminogluthetimide era was unspecific and these substances carried too many side effects for being used clinically. Newer third generation AIs, however, are highly specific and essentially devoid of side effects. These molecules have recently been approved for treating breast cancer in postmenopausal women either, in advanced forms or, as part of adjuvant therapy. In women whose ovaries are active, a temporary inhibition of E2 production will raise gonadotropins and in turn, stimulate follicular growth. In cancer patients, this property precludes the use of AIs in women whose ovaries are still active, unless gonadotropins are blocked. But in infertility patients, this property of AIs has been put to play for inducing ovulation. AIs have been used both in women who do not ovulate but whose hypothalamo-pituitary-gonadal (HPG) axis is active (oligo-anovulators of PCOD type) and those who ovulate regularly but in whom multiple ovulation is sought for treating unexplained infertility or as part of IVF. Like clomiphene citrate (CC), AIs are not usable in women whose gonadotropins are suppressed, as in the case of hypothalamic amenorrhea. The sum of data available on the use of AI for inducing ovulation remains however meager to this date and is mainly constituted of pilot and non-randomized trials. Yet mounting evidence tends to support AIs' advantages over CC for induction of ovulation. Hence, we think that the likelihood that these drugs will play a key role in induction of ovulation in the future is high. AIs appear particularly interesting for treating unexplained infertility because AI-FSH/hMG regimens are lighter than FSH-only regimens while retaining the high pregnancy rates of these latter treatments.
 ...
PMID:Clinical use of aromatase inhibitors (AI) in premenopausal women. 1868 52

Tamoxifen has been the mainstay of endocrine treatment for early-stage breast cancer in both premenopausal and postmenopausal women for many years. Since 2001, the results of several large, randomized, clinical trials have provided evidence that aromatase inhibitor (AI) therapy, either upfront or in sequence after tamoxifen, improves disease-free survival and, in certain patients, overall survival for postmenopausal patients with hormone receptor-positive breast cancer. Thus far, with relatively short-term follow-up, AIs have been generally safe and well tolerated among the population of patients treated in these adjuvant trials. However, important side effects such as musculoskeletal and bone-related problems, including the risk for osteoporosis and fractures, remain of concern and warrant continued monitoring and follow-up. Several questions regarding the appropriate AI to use and the timing of AI therapy remain unresolved, and ongoing studies will help address these issues. Caution is warranted in the use of AIs in perimenopausal women, including those that develop chemotherapy-induced amenorrhea, and clinical evidence supports the role for AI use in postmenopausal women only. Areas of active investigation include the mechanisms of resistance to endocrine therapy with tamoxifen and AIs and clinical strategies to overcome this resistance.
 ...
PMID:Adjuvant hormonal therapy in peri- and postmenopausal breast cancer. 1688 Feb 31

Increasing interest has emerged in the role of ovarian function suppression, which has shown equivalence to adjuvant CMF (cyclophosphamide, methotrexate, 5-fluorouracil), whether achieved by surgery or irradiation, in breast cancer patients. Studies have suggested temporary amenorrhea can confer benefit in early breast cancer, giving luteinizing hormone-releasing hormone (LH-RH) agonists an advantage over oophorectomy or radiation. Compared with no therapy, LH-RH agonists reduce risks of recurrence and death among women younger than 50 years of age who have hormone receptor-positive tumors. Trials are assessing the benefits of adding LH-RH agonists to aromatase inhibitors, tamoxifen, or after chemotherapy in women remaining premenopausal, and the necessity for adjuvant chemotherapy with combined ovarian ablation and antiestrogen therapy.
 ...
PMID:The role of ovarian ablation in the adjuvant therapy of breast cancer. 1836 58


1 2 3 Next >>