Urinary Excretion Of Luteinizing Hormone Research Articles

A Simple Algorithm is Created for Identifying Intermenstrual Intervals Containing an Oscillatory LH Pattern That Associates With Vasomotor Symptoms Using Daily Urinary LH Excretion in the Study of Women’s Health Across the Nation (SWAN)

Background: A specific and unique pattern of luteinizing hormone (LH) excretion has been associated with vasomotor symptoms (VMS) in early menopausal women. Described as “oscillations” of LH excretion, this pattern is consistent with secretory “surges” of LH followed by pituitary “fatigue”. This pattern has not been observed in non-VMS intermenstrual intervals and supports the concept that a breakdown in the hypothalamic-pituitary ovarian axis feed-back loops leads to extreme and cyclic variations in gonadotropin hormone releasing hormone (GnRH) secretion that stimulates collateral nerves to alter core body temperature. Regardless of the precise mechanism, the pattern of LH secretion, as transduced in daily urine as oscillations, provides the basis for the development and validation of a VMS algorithm. Objective: The purpose of this study was to create a simple algorithm to identify intermenstrual intervals exhibiting oscillatory LH, to facilitate investigations into its associations with VMS and other symptoms during the menopausal transition (MT). Methods: As part of the Study of Women’s Health Across the Nation (SWAN), participants in the Daily Hormone Substudy (DHS) were asked to provide daily urine samples - from which LH, E1c, and PdG were measured - and complete a daily symptoms diary for one menstrual cycle (up to 50 days). Analyses included 144 participants whose first DHS collection did not meet the Kassam criterion for evidence of luteal activity; of these, 61 were assessed by an expert as having oscillatory LH and 83 as non-oscillatory LH. Proposed algorithm-based classifications regarding oscillatory LH included number of days with LH at least 50% of the collection maximum LH (number of large-LH days) and number of days with LH no more than twice the collection minimum LH (number of small-LH days). Agreement of these 2 criteria with rater-assigned oscillatory LH was assessed using nonparametric t-tests and binomial logistic regression. Associations of these with VMS frequency were assessed using Spearman correlations. Results: The number of large-LH days was strongly associated with oscillatory LH: median (interquartile range) = 13 (7,22) for oscillatory collections versus 4 (2, 11) for non-oscillatory collections (p<.0001) but number of small-LH days was unrelated (p=.98). Percentage of collection days with VMS was significantly correlated with number of large-LH days (Spearman r=.37, p<.0001) but not with number of small-LH days (Spearman r=.03, p>.05); adjustment for total collection length had negligible impact. Conclusion: A simple algorithm using urinary LH profiles can be used to identify intermenstrual collections that likely contain intervals of VMS.

Clomiphene citrateの排卵誘発機序に関する研究(特にluteinizing hormoneの動態を中心として)

Clomiphene citrateの排卵誘発機序に関する研究(特にluteinizing hormoneの動態を中心として)

Emergency Contraception With Mifepristone and Levonorgestrel

In Brief OBJECTIVE To study the effect of mifepristone and levonorgestrel on ovarian function and endometrial development in doses effective as emergency contraception. METHODS Twelve fertile women were treated with either 10 mg of mifepristone as a single dose (n = 6) or two doses of 0.75 mg of levonorgestrel, 12 hours apart (n = 6) before and after ovulation. An endometrial biopsy performed during the implantation period was analyzed for endometrial maturation and expression of markers of endometrial receptivity. The markers tested for were integrin α4 and β3, cyclooxygenase-1 and -2, progesterone receptors, Dolichos biflorus agglutinin lectin binding, and pinopodes. Urinary excretion of luteinizing hormone, estrone, and pregnanediol were also determined RESULTS Treatment with mifepristone and levonorgestrel before ovulation inhibited the luteinizing hormone surge showing no significant differences between the means of luteinizing hormone measurements. When mifepristone was administered in the early luteal phase, downregulation of progesterone receptors was inhibited in five of six women. No significant alteration was found in any of the remaining markers of endometrial receptivity. CONCLUSION The mode of action of emergency contraception with mifepristone or levonorgestrel is primarily due to inhibition of ovulation rather than inhibition of implantation. Emergency contraception with mifepristone and levonorgestrel acts mainly by inhibition of ovulation rather than inhibition of implantation.

Emergency contraception with mifepristone and levonorgestrel: mechanism of action

OBJECTIVE: To study the effect of mifepristone and levonorgestrel on ovarian function and endometrial development in doses effective as emergency contraception. METHODS: Twelve fertile women were treated with either 10 mg of mifepristone as a single dose ( n = 6) or two doses of 0.75 mg of levonorgestrel, 12 hours apart ( n = 6) before and after ovulation. An endometrial biopsy performed during the implantation period was analyzed for endometrial maturation and expression of markers of endometrial receptivity. The markers tested for were integrin α4 and β3, cyclooxygenase-1 and -2, progesterone receptors, Dolichos biflorus agglutinin lectin binding, and pinopodes. Urinary excretion of luteinizing hormone, estrone, and pregnanediol were also determined RESULTS: Treatment with mifepristone and levonorgestrel before ovulation inhibited the luteinizing hormone surge showing no significant differences between the means of luteinizing hormone measurements. When mifepristone was administered in the early luteal phase, downregulation of progesterone receptors was inhibited in five of six women. No significant alteration was found in any of the remaining markers of endometrial receptivity. CONCLUSION: The mode of action of emergency contraception with mifepristone or levonorgestrel is primarily due to inhibition of ovulation rather than inhibition of implantation.

Urinary excretion of LH and testosterone from male rats during exposure to increased gravity: post-spaceflight and centrifugation.

A dissociation between plasma luteinizing hormone (LH) and testosterone (T) appears to exist during exposure to altered gravity. The pulsatile nature of LH release and the diurnal variability of T secretion may mask or bias the effects of altered gravity on the pituitary-gonadal axis when analyzing plasma concentrations. Therefore, we examined the relationship between the excretion of urinary LH and T in male Sprague-Dawley rats during exposure to increased gravity upon return to Earth following a 14-day spaceflight (n = 6) and by 12 days of centrifugation at 2g (n = 8). Excreted LH and T were elevated on the first 3 days postflight. Excreted T was elevated between Days 1 and 8 of centrifugation; however, excreted LH was reduced on Days 2 and 3 compared with control animals. Excreted LH and T were significantly correlated (R = 0.731 and 0.706, respectively) in postspaceflight and centrifuged animals. Correlation curves had similar slopes (0.0213 and 0.023, respectively), but different y-intercepts (-1.43 and 3.32, respectively). The sustained increase in excreted T during centrifugation suggests that the pituitary-gonadal axis in postspaceflight animals may adapt quicker to increased gravity. The upward shift in the correlation curve exhibited by the centrifuged animals suggests that the sensitivity of LH-induced T release is increased in these animals. The previous dissociation between plasma LH and T during altered gravity was not observed in the present study in which excreted LH and T were measured.

Effect of the menstrual cycle on energy and nutrient intake

Midfollicular and midluteal dietary intakes of 18 women were evaluated between four and six ovulatory menstrual cycles. Phase lengths were established by basal body temperatures and urinary luteinizing hormone excretion. Midfollicular and midluteal diet records were collected 6-8 d after menstrual onset and 6-8 d after ovulation, respectively. Significant increases in energy [0.66 MJ (159 kcal), P = 0.003], protein (6.1 g, P = 0.02), carbohydrate (15.3 g, P = 0.04), and fat (8.6 g, P = 0.002) intakes were observed in midluteal phase when compared with midfollicular phase. Intakes of vitamin D, riboflavin, potassium, phosphorus, and magnesium also were significantly higher during midluteal phase (P < 0.05). These results support the regulation of food intake by menstrual cycle hormones and suggest that it is essential to consider phase of menstrual cycle in studies of nutrient intake performed in premenopausal women.

Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage.

Polycystic ovary syndrome is associated with hypersecretion of luteinizing hormone (LH) which has been implicated in the aetiology of early pregnancy loss. Although 82% of women with recurrent early loss have polycystic ovaries on ultrasound imaging, random serum LH concentrations are normal. In the present study, we have obtained further information from serial samples concerning the cyclical patterns of gonadotrophin and sex steroid secretion in these women. Twenty-one women with recurrent early pregnancy loss and 10 multiparous controls were investigated; 81% of them and one of ten control subjects had polycystic ovaries. Mean mid-follicular and mid-luteal serum LH and follicle stimulating hormone (FSH) levels were similar in both groups. Seventeen women with pregnancy loss had either raised urinary LH excretion or a premature LH surge; one control subject had a premature LH surge. Total LH excretion during the cycle and mean follicular phase serum testosterone was significantly greater with early pregnancy loss than in the control group, the difference in LH being greatest in the early luteal phase. Urinary oestrone-3-glucuronide excretion was raised in the early luteal phase of the cycle in the group with early pregnancy loss; there was no difference between the groups in pregnanediol-3 alpha-glucuronide excretion. These data demonstrate abnormalities in LH secretion in 81% of women with recurrent fetal loss. Inappropriately raised LH levels may have adverse effects on the developing oocyte or endometrium either directly, or indirectly by causing an elevation in testosterone and oestrogen levels.

Subclinical alterations in hormone and semen profile in athletes

To investigate the effects of two forms of exercise, endurance training (running) and resistance training (weight lifting), on reproductive function in male athletes. Cross-sectional study. Reproductive Endocrinology and Exercise Laboratory. Twenty-eight healthy male volunteers, 18 to 35 years of age, including 10 endurance-trained runners, 8 resistance-trained weight-lifters, and 10 sedentary controls. Hormonal evaluation included determination of plasma levels of total testosterone (T), serum levels of free T, luteinizing hormone (LH), follicle-stimulating hormone, prolactin, and estradiol, and urinary excretion of LH. Semen analyses included an evaluation of sperm characteristics in terms of density, count, motility, and morphology, and a determination of in vitro sperm penetration of standard bovine cervical mucus. Compared with sedentary controls, endurance-trained and resistance-trained athletes presented with significantly lower levels of total and free T. There were no significant differences in the serum levels of all other circulating and urinary hormone measurements among the three groups. Sperm density, motility, and morphology were significantly altered only in the endurance-trained runners. In vitro sperm penetration of standard cervical mucus was significantly reduced in the endurance-trained runners. Both endurance and resistance training modify the male reproductive hormone profile in a similar manner; however, only endurance training, in the form of running, is associated with subclinical modifications in semen characteristics.

The pituitary-testicular axis at rest and during moderate exercise in males with diabetes mellitus and normal sexual function.

Hormonal studies of pituitary-testicular function in insulin-dependent diabetes mellitus were examined at rest and during moderate exercise to assess whether diabetes per se caused abnormalities of nocturnal penile tumescence and androgen function in men with normal sexual function. The present study compared 10 healthy men and eight men with Type I diabetes mellitus in whom normal sexual function was determined by clinical history. Urinary gonadotropin excretion, semen analysis and diurnal variation of serum glucose, prolactin, testosterone and free testosterone were determined in both groups. In addition, the serum levels of testosterone, free testosterone, prolactin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured at rest, during 45 minutes of exercise on a bicycle ergometer at 50% of the subjects previously determined maximal oxygen uptake (VO2 max) and during a 30-minute recovery period. Nocturnal penile tumescence and parameters of semen analysis were similar in both groups. Urinary FSH excretion and serum FSH were higher (P less than or equal to 0.01) in the diabetic subjects while urinary LH excretion was similar. Diurnal variation of serum prolactin, testosterone and free testosterone were similar in both groups. Exercise produced a significant (P less than or equal to 0.01) increase in maximal free and total testosterone in both groups without changes in serum FSH or LH. Prolactin increased significantly (P less than or equal to 0.01) during exercise in the diabetic group only. We conclude that, for the most part, the pituitary-testicular axis and nocturnal penile tumescence under basal conditions and the pituitary-testicular axis during moderate exercise are similar in healthy males and insulin-dependent diabetic males with normal sexual function.

The interrelationship between sex skin swelling and the urinary excretion of LH, estrone, and pregnanediol by the cycling female chimpanzee.

The interrelationship between sex skin swelling and the urinary excretion of luteinizing hormone and sex steroids was investigated during ovulatory menstrual cycles in adult female chimpanzees. Estrone was excreted in two peaks, one during the preovulatory and the other during the midluteal phase. Maximum swelling of the sex skin was attained several days before the preovulatory estrone peak. The LH surge preceded or accompanied beginning detumescence of the sex skin which, in turn, was closely correlated with a rising excretion of pregnanediol. Urinary measurements provide integrated estimates of the concentration of fluctuating hormones and, in addition, are safer and easier to make than blood measurements in this species.

Clinical investigation of the biological effects of a new combination low-dose oral contraceptive (‘Ovostat E’)

A low-dose contraceptive containing 1 mg of lynestrenol and .05 mg of ethinyl estradiol was studied over 12 cycles in 11 healthy fertile women volunteers. The subjects were aged 20-30 years. Measurements were taken of urinary luteinizing hormone (LH), pregnanediol, and estrogen, and serum progesterone and estradiol values; in addition, on a fixed schedule during treatment, the 3rd, 5th, 7th, and 12th months, vaginal smears and endometrial biopsies were taken, along with SGOT and SGPT determinations. According to determinations, ovulation was inhibited during every cycle tested. A clear estrogenic effect was evident in the karyopyknotic index, during cycle 3, at the beginning of the cycle which became a progestational effect around Day 13 (biphasic). In cycle 6, the indexes of cytology decreased, but during Cycle 12, they rose a bit again. Basal body temperature during treatment was monophasic. Cervical mucus assessed by spinnbarket during treatment was low and arborization absent. The SGOT and SGPT liver function tests were within normal values in all cycles in 7 women; 4 showed clearly higher levels in Cycles 3 and 12. None of the cycles showed the high midcycle urinary excretion of LH. No significant side effects were reported. Examination of the endometrial biopsies showed a drug effect in all cases and there was no secretory activity in any of the samples. These findings confirm clinical results that show this low-dose combination to be an effective contraceptive agent.

Effects of a low-oestrogen oral contraceptive on urinary excretion of luteinizing hormone and ovarian steroids.

The urinary gonadotrophin and ovarian steroid excretion pattern was studied in five women taking an oral contraceptive formulation consisting of mestranol 50 mug and norethisterone 1 mg. Both the pretreatment and post-treatment cycles were normal. The ovulatory peak of luteinizing hormone (LH) during the treatment cycles was uniformly suppressed, but LH continued to be excreted within the normal range. In one fifth of the treatment cycles there was a pronounced and sustained rise of oestrogen output in the absence of ovulation, and in many of the other treatment cycles oestrogen levels suggested that active ovarian steroidogenesis was taking place.

Effects of continuous daily administration of 0.1 mg of norethindrone on the plasma levels of progesterone and on the urinary excretion of luteinizing hormone and total oestrogens.

ABSTRACT Daily determinations of the plasma level of progesterone and the urinary excretion of LH and oestrogens were performed in four women during one control cycle followed by three months of daily treatment with 0.1 mg of norethindrone. According to the plasma progesterone pattern, all four women seemed to ovulate during their control cycle. Two women became pregnant during their second cycle of treatment. During treatment all four women showed an atypical LH pattern without any distinct midcycle peak. The mean LH excretion during treatment was not significantly different from the mean level of follicular phase of normal cycles. The oestrogens and progesterone levels were within normal ranges. It is concluded that during treatment with 0.1 mg of norethindrone daily an apparently normal pregnancy may occur in spite of a different LH excretion pattern.

Urinary excretion of luteinizing hormone in girls and normal menstruating women.

SummaryThe 24‐hour urinary excretion of luteinizing hormone (LH) was determinded in 24 girls, aged 4 to 11 years, and in 15 normal menstruating women, aged 18 to 44 years, by an immunological method using the haemagglutination inhibition reaction after a tannic acid extraction. LH was detected in every subject investigated. The mean value for urinary LH excretion in girls was equivalent to 3.8 i.u. (2nd IRP‐HMG) per 24 hours (range 1.2–8.0) and was 29.8 i.u. per 24 hours (range 24.0 to 38.0) in adult women. In girls the LH output increased significantly with age. In normally menstruating adult women, the LH output increased slightly but not significantly with age.

Luteinizing hormone (LH) and progesterone in plasma and LH and oestrogens in urine during 42 normal menstrual cycles.

ABSTRACT The plasma levels of luteinizing hormone (LH) and progesterone and the urinary excretion of LH and oestrogens were measured during the normal menstrual cycle of 22 young and healthy women. A total of 42 cycles were investigated. The urinary excretion of total oestrogens increased during several days before the rise of LH in the urine. The day of maximum excretion of LH and total oestrogens coincided during the midcycle period. The mid-cyclic rise in LH was found to occur on the same day in the plasma and urine and the days of maximum values coincided in 11 out of 16 cycles. In 5 cycles the maximum level was reached one day later in the urine. The plasma levels of progesterone started to increase during the LH and oestrogen peaks. The days for maximum levels of progesterone coincided with the second peak of urinary oestrogens. The levels of progesterone in the plasma reached values above 10 ng per ml in all normal cycles. The plasma levels of progesterone were below 1 ng per ml plasma when menstrual bleeding started. The length of the luteal phase was 14.4 ± 1.1 (s) days. The sum of daily urinary excretion of total oestrogens and the sum of the daily plasma progesterone levels varied within 15 per cent of the mean in five out of six women studied during more than two cycles. The variation in values for the sums of daily oestrogen excretion and plasma progesterone levels was considerably larger between menstrual cycles of different women than between menstrual cycles of the same woman.

Effects of continuous daily administration of 0.5 mg of chlormadinone acetate on the plasma levels of progesterone and on the urinary excretion of luteinizing hormone and total oestrogens.

ABSTRACT Daily determinations of the plasma level of progesterone and the urinary excretion of luteinizing hormone (LH) and total oestrogens were performed in 6 subjects during one control cycle, immediately followed by three cycles of daily treatment with 0.5 mg of chlormadinone acetate continuously. The control cycles were ovulatory according to the parameters investigated. Two of the women showed a normal LH excretion pattern in all treatment cycles. The four other subjects also had periodical variations in the LH excretion but no distinct midcycle peaks occurred. The mean oestrogen excretion was increased in all three treatment cycles but the difference was satistically significant only in the last two cycles. Compared with the treatment cycles, the sum of progesterone values was significantly decreased in the first two cycles. Chlormadinone acetate in this dose had no thermogenic effect. Three of the subjects showed bleeding irregularities which had no clear connection with the hormone variations measured in the study. It is suggested that the low levels of progesterone might be due to a defective corpus luteum function.

A modification of the OAAD test for luteinizing hormone for clinical purposes.

ABSTRACT A modification of the ovarian ascorbic acid depletion (OAAD) assay for the luteinizing hormone (LH) is described in which the standard and the test materials are administered subcutaneously (sc) rather than intravenously (iv) with testicular hyaluronidase as a diffusion factor. The depletion curves for increasing doses of LH administered by either technique are practically identical. The slope of the log dose response curve and the index of precision of the modified method are satisfactory. The method has been applied to the assay of crude urinary extracts obtained by the Johnsen procedure (Johnsen 1958) and the values obtained for the urinary excretion of LH in different physiological states are presented.

Urinary excretion of luteinizing hormone in boys and adult men.

SUMMARY The daily urinary excretion of luteinizing hormone (LH) was determined in 15 boys, aged 5–11 yr., and in 15 adult men, aged 18–65 yr., by an immunological method using the haemagglutination inhibition system. The hormone was detected in every subject investigated. The mean value for urinary LH excretion in boys was equivalent to 3·4 i.u./24 hr. (range 1·3–6·5) and was 29·3 i.u./24 hr. in adults (range 15·4–44·6). The mean adult: child ratio was 8·6. There was a significant increase in LH output with age in both the boys and the men; the rate of this increase was the same in both groups. However, there was a sharp rise in hormone output at about the onset of puberty.

Pituitary and ovarian function in women on continuous low dose progestogens; effect of chlormadinone acetate and norethisterone.

ABSTRACT Chlormadinone acetate (6-chloro-17α-hydroxypregna-4,6-diene-3,20-dion-17-acetate; hereafter CAP = chloro-acetoxy-progesterone) was administered continuously in daily oral doses of 0.5 mg to three normally menstruating women and the urinary excretion of luteinizing hormone (LH), oestrone (OE1), 17β-oestradiol (OE2), oestriol (OE3) and pregnanediol (5β-pregnane-3α,20α-diol; hereafter P-diol) was studied. Forty-eight hour specimens were analyzed during a pretreatment cycle, the first and fourth CAP cycles and the first posttreatment cycle. Considerable individual variations were found in all parameters studied. In addition, significant differences were observed in the response of the same subjects to the first and to the fourth course of CAP. A well defined midcycle LH-peak was found in all pretreatment cycles. The administration of CAP abolished the midcycle LH peak in 5 of the 6 treatment courses studied; the »ovulatory« LH peak re-appeared in all subjects during the first posttreatment cycle. The oestrogen and P-diol excretion patterns were often inconsistent with the LH pattern; on several occasions a distinct »ovulatory« oestrogen or P-diol pattern was found in the absence of any midcycle LH peak. Such a P-diol pattern was accompanied by an elevated basal body temperature. A similar study was conducted in two normally menstruating women, before and during the continuous administration of a low dose (0.1 mg/d) of oestrogen-free norethisterone (17α-ethynyl-17β-hydroxy-19-norandrost-4-en-3-one; hereafter NET), followed by a course of a high dose (2.5 mg/d) of NET. The inhibitory effect of NET on LH excretion was less marked than that of CAP. The oestrogen excretion remained rather high. In only one of the two subjects did the administration of 0.1 mg of NET abolish the »ovulatory« P-diol pattern. Elevated P-diol values were not found during the administration of 2.5 mg of NET. The correlation between »ovulatory« LH- and P-diol patterns was rather poor. The data indicate that the continuous administration of low doses of CAP interferes only slightly with oestrogen excretion, but has a marked effect on the midcycle LH-peak. It is concluded that the assertion of ovulation inhibition on the basis of urinary LH- and steroid excretion studies may be associated with major uncertainties. Also, it seems that for a better understanding of the mechanism of contraceptive action of low level progestogens more information is required on the minimal amounts of urinary LH and P-diol, which are still compatible with a normal ovulation and corpus luteum function.

Effect of 6α-methyl-17α-hydroxyprogesterone on urinary excretion of luteinizing hormone

In order to determine the mechanism whereby intramuscular injection of a long-acting medroxyprogesterone inhibits ovulation, daily immunoassay of urinary excretion of LH was performed on 4 subjects. During two control cycles prior to treatment, a midcycle peak of LH excretion was observed at the approximate time of ovulation in all subjects. After treatment with 150mg. of Depo-Provera, there was no peak of LH excretion observed in any subject during the time the drug was active. In the two subjects who had assays continued until ovulation resumed, there was again evidence of a peak in LH excretion at the time of ovulation. This study indicates that medroxyprogesterone acetate administered in this dosage acts as a contraceptive by inhibiting release of LH.