Pregnanediol Glucuronide Excretion Research Articles

The Use of Estrone-3-Glucuronide and Pregnanediol-3-Glucuronide Excretion Rates to Navigate the Continuum of Ovarian Activity.

The patterns of a woman's normal ovarian activity can take many forms from childhood to menopause. These patterns lie on a continuum ranging from no ovarian activity to a fully fertile ovulatory cycle, but among the other defined patterns are cycles with anovulatory ovarian activity, including luteinized unruptured follicles (LUFs), and ovulatory cycles with deficient or short luteal phases. For any woman, these patterns can occur in any order, and one can merge into the next, without an intervening bleed, or be missed entirely. Consequently, it is not yet possible to predict the pattern of a future cycle, but it is possible to use our knowledge of the continuum to interpret the current cycle, which has clear implications for the management of personal fertility. An individual's position in the continuum can be monitored directly in real time by daily monitoring of ovarian hormone excretion rates, without either calendar-type calculations or reference to population means and standard deviations. The excretion of urinary estrone glucuronide (E1G) gives a direct measure of follicular growth, and the post-ovulatory rise in urinary pregnanediol glucuronide (PdG) following an E1G peak provides good evidence of ovulation. Specific values of the PdG excretion rate can be used to determine whether a cycle is anovulatory with or without a LUF, or is ovulatory and infertile or ovulatory and fertile. These specific values are important signposts for navigating the continuum. For a woman to take advantage of the knowledge of the continuum, the data must be reliable, and their interpretation has to be based on the underlying science and provided in an appropriate form. We discuss the various factors involved in acquiring and providing such information to enable each woman to navigate her own reproductive life.

Establishment of a reference ELISA for measurement of universal thresholds of pregnanediol glucuronide excretion rates using urine samples diluted to a constant volume per unit time

ABSTRACTAn enzyme-linked immunosorbent assay (ELISA) for measurement of pregnanediol-3α-glucuronide (PdG) excretion rates in urine samples diluted to 150 mL/h before analysis is described. The sensitivity of the 9 optimized standard curves was 0.093 ± 0.070 μmol PdG/24 hr, with the multiple combined standard curves having a mean mid-point (EC50) of 6.88 μmol PdG/24 hr. The PdG threshold excretion rate of 7.0 μmol/24 hr, which is used as a marker for the end of fertility, was situated in the most accurate region of the standard curve. The specificity of the ELISA was determined using normal variate transformation to compare seven menstrual cycle profiles obtained with the ELISA method with the profiles obtained previously using a validated radioimmunoassay (RIA) method. The cycle profiles all agreed within experimental error, and a high degree of correlation using Deming regression was obtained. The correlation equation was Y = 1.57X-0.11 μmol PdG/24 hr (n = 200; r = 0.932). The PdG excretion rates determined by the ELISA were 50% higher than given by RIA, but the normal ranges were similar to those given by the original reference gas liquid chromatographic method. The ELISA assay was therefore suitable as a reference method for measurement of thresholds of PdG excretion rates.

Monitoring of ovarian activity by measurement of urinary excretion rates using the Ovarian Monitor, Part IV: the relationship of the pregnanediol glucuronide threshold to basal body temperature and cervical mucus as markers for the beginning of the post-ovulatory infertile period.

Do the basal body temperature (BBT) shift and the cervical mucus markers for the beginning of the post-ovulatory infertile phase (POIP) of a menstrual cycle agree with the corresponding urinary pregnanediol glucuronide (PdG) threshold value? Perfect agreement between the cervical mucus markers and BBT shift and the hormonal definition of the start of post-ovulatory infertility occurred for only 7-17% of the cycles. The PdG threshold of 7.0 µmol/24 h is an objective and accurate marker for the beginning of the POIP. The rise in serum progesterone also produces the BBT shift and changes in cervical mucus which determine the mucus peak. Serum progesterone and urinary PdG are closely correlated when variations in urine volume are taken into account. Individual menstrual cycle profiles of urinary PdG excretion rates for 91 fertile cycles from normally cycling women were analysed to identify the day of the beginning of the POIP. These days were compared with those determined by the day of the BBT shift +2 days, the day of the mucus peak +4 days and the later of these two indicators. The study lasted 3 years. A total of 62 women with normal menstrual cycles were recruited from three centres: Palmerston North, New Zealand; Sydney, Australia and Santiago, Chile. The cycles were displayed individually in a proprietary database program which recorded the PdG excretion rates, the BBT shift day and the cervical mucus peak day. A group of 15 women from a separate Chilean study had PdG urinary data measured as well as their day of ovulation determined by ultrasound. The BBT and cervical mucus markers differed significantly in their identification of the beginning of the POIP when compared with the PdG excretion rate of 7.0 µmol/24 h. The observation that the BBT shift day and the mucus peak day could be identified even though the PdG excretion rates were still at baseline levels in some cycles could lead to an unexpected pregnancy for women using these natural family planning (NFP) indicators. The study consisted only of fertile cycles from women with regular cycles of 20-40 days duration. All the women were intending to avoid a pregnancy during the study, thus the limits of the fertile window were not tested. The NFP signals occurring earlier than the PdG threshold day could lead to an unexpected pregnancy. The signals occurring on the same day or later than the PdG threshold would not lead to unexpected pregnancies, but would require extra abstinence that could lead to non-compliance with the NFP method. A possible improvement in reliability of NFP methods is suggested. This study (project #90905) was funded by the NDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP). D.G.C. currently works for a diagnostic development company, Science Haven Ltd. The other authors have nothing to declare.

Monitoring of ovarian activity by daily measurement of urinary excretion rates of oestrone glucuronide and pregnanediol glucuronide using the Ovarian Monitor, Part III: Variability of normal menstrual cycle profiles

What are the characteristics of, and how variable are, individual normal menstrual cycle profiles of excretion rates for the urinary metabolites oestrone glucuronide (E1G) and pregnanediol glucuronide (PdG)? There is a continuum of menstrual cycle profiles that differ from standard textbook profiles but which can be understood simply in terms of growth, atresia and ovulation of ovarian follicles. Point-of-care assays with the Ovarian Monitor pre-coated assay tubes, using urine samples diluted to a constant volume per unit time, give laboratory accurate clinical data for individual menstrual cycles. Lay operators can perform the point-of-care assay system at home to achieve reliable and reproducible results, which can be used for natural family planning. This prospective study involved 62 women, with normal menstrual cycles, recruited from three centres: Palmerston North, New Zealand, Sydney, Australia and Santiago, Chile. The study lasted 3 years. Women collected daily urine samples and determined their E1G and PdG rates with a pre-coated enzyme assay system known as the Ovarian Monitor. For two cycles, the assays were repeated in a study centre and the results were averaged to give 113 individual menstrual cycles for analysis. The cycles were displayed individually in a proprietary database program. The individual normal hormonal profiles were more complex than the classic composite curves for 40% of the cycles. Of 113 ostensibly normal cycles, only 91 were potentially fertile and 22 had some luteal phase defect. The oestrone glucuronide and PdG excretion rates were reliable and informative in the non-invasive elucidation of ovulation and ovarian function for both simple and complex profiles. Daily monitoring revealed the variability of normal menstrual cycle profiles. The LH peaks were variable and ambiguous markers for ovulation. The study consisted of cycles only from women with regular cycles of 20-40 days duration. All the women were intending to avoid a pregnancy during the study thus the limits of the fertile window were not tested. The principles established in this study should apply to cycles of any length. All peaks in oestrone glucuronide excretion should be tested by concurrent measurements of PdG, which gives a positive indication of the fate of the follicle it represents. The Ovarian Monitor provides a useful addition for practitioners of natural family planning. Financial support for this study was obtained from the UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction (HRP). D.G.C. is currently employed by and holds stock in Manawatu Diagnostics Ltd, a company in the development phase of a potentially competing product. The remaining authors have nothing to declare.

Describing ovarian cycles, pregnancy characteristics, and the use of contraception in female white-faced marmosets, Callithrix geoffroyi.

Endocrine data and characteristics of nonconceptive ovarian cycling and pregnancy are limited within the genus Callithrix to the common marmoset (C. jacchus) and Wied's black tufted-ear marmoset (C. kuhlii). This article presents patterns of urinary pregnanediol-3-glucuronide (PdG) excretion, as determined by enzyme immunoassay, throughout the course of ovarian cycling and pregnancy in white-faced marmosets (C. geoffroyi). Furthermore, characteristics of reproductive parameters including litter size, duration of gestation, maternal age, and information about ovarian cycling following administration of contraceptives are also described. A steep increase in PdG, an indication of ovulation, characterizes normative ovarian cycles, with peak-to-peak intervals between cycles being 27.82 ± 1.49 days in length. PdG excretion (μg/mg Cr) across pregnancy peaked during the 1st and 2nd trimesters (1st = 20.71 ± 2.98, 2nd = 21.16 ± 2.60) and declined gradually to near preconception levels over the 3rd trimester until parturition (3rd = 5.74 ± 1.60). Gestation lasted 148.55 ± 1.89 days. Most pregnancies (82.8%) resulted in an immediate postpartum ovulation (PPO) of 17.45 ± 2.22 days with 58.3% of PPOs resulting in conception. No differences in PdG excretion during the 1st trimester between full pregnancies and miscarriages were found, and pregnancy characteristics such as litter size, duration of gestation, and maternal age were not associated with PdG concentrations. Administration of cloprostenol resulted in shorter peak-to-peak cycle durations, but ovulation was detectable with similar concentrations of peak PdG to a normal nonconceptive cycle. Conversely, medroxyprogesterone acetate (DMPA) injections resulted in little to no PdG excretion across the ovarian cycle. Both methods of contraception providing effective prevention of conception. Overall, these results show that strong similarities in reproductive parameters persist within the genus Callithrix and to a lesser extent across the Callitrichidae family.

Effects of Antenatal Corticosteroids on Urinary Markers of the Initiation of Lactation in Pregnant Women

Antenatal corticosteroids are given to most women at risk of preterm delivery, although many do not eventually deliver preterm. Profound disruptions of lactation have been shown in ewes after antenatal corticosteroid treatment, but little is known of the effect on lactation in women. This study aimed to investigate the effects of antenatal corticosteroid treatment on mammary secretion during pregnancy in women. We conducted a prospective cohort study of women receiving betamethasone for anticipated preterm delivery (n = 87). Women collected 24-hour urine samples on days 1, 2, 3, 5, 7, and 14 after treatment if they remained pregnant. We measured urinary excretion of pregnanediol glucuronide (PdG), a major metabolite of progesterone and lactose, which indicates mammary secretion during pregnancy. Withdrawal of progesterone triggers the onset of mammary secretion. Median (range) gestational age at treatment was 28.8 (23.6-33.6) weeks. A total of 330 24-hour urine samples were collected. Median (range) excretion of PdG was 1.355 (0.139-5.069) mmol/24 hours, and lactose excretion was 0.823 (0.035-6.676) mmol/24 hours. Both PdG and lactose excretion increased with increasing gestational age (P < 0.001). After adjustment for gestational age, there were significant transient increases in lactose excretion (P < 0.001) after betamethasone treatment but no changes in PdG excretion (P = 0.435). Antenatal betamethasone treatment was associated with a transient premature secretory activation while women were still pregnant.

Hormonal monitoring of ovarian activity using the Ovarian Monitor, Part I. Validation of home and laboratory results obtained during ovulatory cycles by comparison with radioimmunoassay

A study was conducted to determine the accuracy and reliability of the Home Ovarian Monitor for measuring estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) during ovulatory cycles as a means of monitoring ovarian activity. Approximately 60 ovulating women in three centres collected timed specimens of urine (3 h or more) for a total of six cycles each. The women measured the E1G and PdG excretion per 24 h in their urine specimens using the Monitor. A local laboratory using the Monitor also measured the excretion. Urine specimens from 18 to 19 cycles were sent frozen to the WHO Reference Laboratory in London where they were analysed for E1G and PdG by the Monitor and by radioimmunoassay (RIA). The correlation coefficients between the Monitor and radioimmunoassay results obtained in London were better than 0.84 in 80% of the cycles. A urine bias caused the Monitor E1G results to be higher than those obtained by radioimmunoassay but the daily patterns were the same. In 50% of the cycles, this bias caused a delay of up to 3 days in identifying the beginning of the E1G rise compared with radioimmunoassay. Timing of the preovulatory E1G peak and the postovulatory PdG rise agreed within the experimental errors of the two systems. The study confirmed that women using the Monitor at home obtained results that were as accurate as those obtained by laboratory procedures. Careful supervision was required to maintain laboratory levels of quality control and interpretation of results.

An effective, economic way of monitoring menstrual cycle hormones in at risk female athletes.

Female athletes, in response to intensive training, competition stress and a lean, athletic physique, are at increased risk of altered hypothalamic-pituitary ovarian (HPO) axis function associated with menstrual cycle disturbance and reduced secretion of the ovarian hormones estrogen and progesterone. Because there is evidence suggesting possible detrimental effects on skeletal health associated with deficiencies in these hormones, a suitable means to asses ovarian hormone concentrations in at risk athletes is needed. The aim of this study was to evaluate a simple, economical means to monitor the ovarian hormone production in athletes, in the setting of intensive training. Subjects comprised 14 adolescent rowers, 12 lightweight rowers, and two groups of 10 matched control subjects. Ovarian function was monitored during the competition season by estimation of urinary excretion of estrone glucuronide (E1G) and pregnanediol glucuronide (PdG), enabling the menstrual cycles to be classified as ovulatory or anovulatory. Results indicated 35% and 75% of schoolgirl and lightweight rowers had anovulatory menstrual cycles, respectively. These findings were highlighted by significantly lower excretion of E1G and PdG during phases of intensive training in both the lightweight and schoolgirl rowers, compared with the control subjects. It was concluded that the urinary E1G and PdG assays were an effective means to assess the influence of intense training on ovarian hormone concentrations in at risk athletes. It is recommended that this technique be applied more widely as a means of early detection of athletes with low estrogen and progesterone levels, in an attempt to avoid detrimental influences on skeletal health.

Prospective decrease in progesterone concentrations in female lightweight rowers during the competition season compared with the off season: a controlled study examining weight loss and intensive exercise.

The purpose of this study was to monitor ovarian hormone function response to intense exercise and body weight changes in female athletes. Ovarian hormone function was evaluated in 12 female...

High frequency of luteal phase deficiency and anovulation in recreational women runners: blunted elevation in follicle-stimulating hormone observed during luteal-follicular transition.

The purposes of this investigation were to evaluate the characteristics of three consecutive menstrual cycles and to determine the frequency ofluteal phase deficiency (LPD) and anovulation in a sample of sedentary and moderately exercising, regularly menstruating women. For three consecutive menstrual cycles, subjects collected daily urine samples for analysis of FSH, estrone conjugates (E1C), pregnanediol-3-glucuronide (PdG), and creatinine (Cr). Sedentary (n=11) and exercising (n=24) groups were similar in age (27.0+/-1.3 yr), weight (60.3+/-3.1 kg), gynecological age (13.8+/-1.2 yr), and menstrual cycle length (28.3+/-0.8 days). Menstrual cycles were classified by endocrine data as ovulatory, LPD, or anovulatory. No sedentary women (0%) had inconsistent menstrual cycle classifications from cycle to cycle, but 46% of the exercising women were inconsistent. The sample prevalence of LPD in the exercising women was 48%, and the 3-month sample incidence was 79%. In the sedentary women, 90% of all menstrual cycles were ovulatory (SedOvul; n=28), whereas in the exercising women only 45% were ovulatory (ExOvul; n=30); 43% were LPD (ExLPD; n=28), and 12% were anovulatory (ExAnov; n=8). In ExLPD cycles, the follicular phase was significantly longer (17.9+/-0.7 days), and the luteal phase was significantly shorter (8.2+/-0.5 days) compared to ExOvul (14.8+/-0.9 and 12.9+/-0.3 days) and SedOvul (15.9+/-0.6 and 12.9+/-0.4 days) cycles. Luteal phase PdG excretion was lower (P < 0.001) in ExLPD (2.9+/-0.3 microg/mg Cr) and ExAnov (0.8+/-0.1 microg/mg Cr) cycles compared to SedOvul cycles (5.0+/-0.4 microg/mg Cr). ExOvul cycles also had less (P < 0.01) PdG excretion during the luteal phase (3.7+/-0.3 microg/mg Cr) than the SedOvul cycles. E1C excretion during follicular phase days 2-5 was lower (P=0.05) in ExOvul, ExLPD, and ExAnov cycles compared to SedOvul cycles and remained lower (P < 0.02) in the ExLPD and ExAnov cycles during days 6-12. The elevation in FSH during the luteal-follicular transition was lower (P < 0.007) in ExLPD (0.7+/-0.1 ng/mg Cr) cycles compared to SedOvul and ExOvul cycles (1.0+/-0.1 and 1.1+/-0.1 ng/mg Cr, respectively). Energy balance and energy availability were lower (P < 0.05) in ExAnov cycles than in other menstrual cycle categories. The blunted elevation in FSH during the luteal-follicular transition in exercising women with LPD may explain their lower follicular estradiol levels. These alterations in FSH may act in concert with disrupted LH pulsatility as a primary and proximate factor in the high frequency of luteal phase and ovulatory disturbances in regularly menstruating, exercising women.

Comparison of endometrial biopsy and urinary pregnanediol glucuronide concentration in the diagnosis of luteal phase defect

To determine if pregnanediol glucuronide (PG) excretion is useful in luteal phase assessment, we compared daily first morning urinary PG concentrations during the luteal phase in nine normal and nine deficient cycles. Total luteal pregnanediol excretion (44.1 +/- 11.3 versus 64.0 +/- 11.6 area units +/- SEM) was not different. However, significantly less pregnanediol was excreted by the abnormal group during the 1st 5 days of the luteal phase (12.7 +/- 1.2 versus 18.0 +/- 1.7 area units +/- SEM, respectively). Thus, delayed PG excretion may be characteristic of luteal phase defect and measurement of urinary PG may be useful only if daily samples during the early luteal phase are obtained.

Ovarian function in premenopausal women affected by breast cancer: The measurement of glucuronoconjugate metabolites of 17β-estradiol and progesterone throughout one entire menstrual cycle

For many years, hypersecretion of estrogens has been suspected of being one of the major risk factors of breast cancer for premenopausal women. Seventeen premenopausal women, who had undergone lumpectomy because of breast cancer (T1a No Mo) 3 yr before entering the study, were compared to 9 normal women of similar age, parity and body weight. A chemiluminescent method was used for the determination of estrone-3-glucuronide (E1-3G) and pregnanediol-3-glucuronide (Pd-3G) in early morning urine samples collected for an entire menstrual cycle of each of the 26 subjects. During the follicular phase, no significant differences in E1-3G and/or Pd-3G excretion were found between the two groups. During the luteal phase the E1-3G/Pd-3G ratio in the early, middle and late luteal phase had significantly increased in the women with breast cancer, in spite of normal Pd-3G excretion. Therefore, the measurement of glucuronoconjugate metabolites of ovarian hormones in overnight urine might be conveniently applied to the study of ovarian function in subjects with breast cancer. Furthermore, the results of this study may indicate that an estrogen/progesterone imbalance is an additional risk factor for the premenopausal breast cancer patient.

The development of an enzyme‐immunoassay for urinary pregnanediol‐3‐glucuronide and its application to reproductive assessment in exotic mammals

Measurement of urinary pregnanediol‐3‐glucuronide (PdG) provides a practical, non‐invasive method for monitoring ovarian function and pregnancy in diverse mammalian species. To date, however, methods of laboratory analysis have relied on radio‐immunoassay procedures which, because of their cost and the problems associated with the use and disposal of radioactive substances, have limited potential for routine application in zoos and other animal collections with limited laboratory facilities. The present paper reports the development of a non‐isotopic enzyme‐immunoassay for the measurement of urinary PdG in a wide range of exotic mammals and describes its application to reproductive assessment in the gorilla and rhinoceros.The assay is based on an homologous competitive binding system and utilizes antiserum raised against PdG‐bovine serum albumen and alkaline phosphatase‐PdG, prepared by the active ester technique, as conjugate. Sensitivity of the assay is between 12.5 and 25 pg/well and precision, expressed as the intra‐ and inter‐assay coefficients of variation, is between 5.3 and 7.8% and 9.2 and 16.1%, respectively. Serial dilutions of human, gorilla, orang‐utan, mangabey, blackbuck, okapi, gaur, giant panda and Indian, black and white rhinoceros urine gave displacement curves parallel to that of the PdG standard, indicating the potential of the assay for multi‐species application.The pattern of excretion of immunoreactive PdG during successive menstrual cycles and two complete pregnancies in a gorilla is described. Follicular phase levels of PdG were low (0.07–0.13 μg/mg creatinine (Cr)), in contrast to the high levels of excretion during the luteal phase (maximum values 1.5–2.1 μg/mg Cr). Mean cycle length was 29.6±1.5 days with a range of 26–34 (n = 5). The pattern of PdG excretion during pregnancy showed a slow increase during the first 60 days and a more rapid rise to values of 8–12 μg/mg Cr after 120 days, with no further consistent increase during the remaining period of pregnancy. Estimated gestation lengths were 280 and 256 days.The levels of immunoreactive PdG excreted during mid‐to‐late pregnancy varied considerably between the three species of rhinoceros, maximum values ranging from up to 10 μg/mg Cr in the Indian to 0.08 μg/mg Cr in the white rhinoceros. Despite this variation pregnancy was associated with elevated PdG excretion in all three species and each profile showed a marked fall in levels at the end of the gestation period. The results suggest potential for urinary PdG determination as a practical method of pregnancy detection in both Indian and African rhinoceros, although species differences in the relative importance of PdG as a progesterone metabolite probably exist.

Late luteal phase administration of RU486 for three successive cycles does not disrupt bleeding patterns or ovulation.

RU486, a 19-nor steroid, binds with high affinity to the receptors for progesterone and glucocorticoids, blocking the actions of these hormones on their target tissues. We conducted studies to determine whether RU486 administered at the end of the luteal phase would disturb the menstrual rhythm, ovulation, or hormonal parameters in the treatment and post-treatment cycles. The first study was done in six surgically sterilized women during two consecutive cycles. RU486 [17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-(1-propynyl)estra-4,9-dien-3-one; 100 mg/day] was given for 4 consecutive days, commencing on days 23-27 of the first cycle. Menstrual bleeding occurred by the second day of RU486 administration in all women and was indistinguishable from their usual bleeding pattern. The onset of this bleeding was advanced by RU486 administration, since it entailed shortening of the luteal phase with prolongation of the following follicular phase. Serum LH, FSH, estradiol, and progesterone levels were normal in five of the six women in both the treatment and posttreatment cycles. The second study was conducted in 10 women who were not exposed to the risk of pregnancy. RU486 (100 mg/day) was given for 4 consecutive days, commencing 4 days before their expected menses for 3 successive cycles, preceded and followed by 2 placebo-treated cycles. Bleeding patterns were indistinguishable during the RU486 and placebo cycles. Late luteal phase administration of RU486 consistently produced menstrual bleeding within 1-3 days of drug administration. Daily early morning urinary LH excretion in 6 women and estrone glucuronide and pregnanediol glucuronide excretion in 5 women during both placebo and RU486 cycles were consistent with luteinization, suggesting ovulation and appropriate corpus luteum function. We conclude that RU486 has no major effect on menstrual cycle events if given at the time of the natural progesterone withdrawal that occurs before menses in nonpregnant women.

Melatonin: data consistent with a role in controlling ovarian function.

FSH and LH excretion were correlated with melatonin excretion in consecutive daily urines obtained from a normal adult female (27 days), a normal 11-year-old girl (28 days), and an 8-year-old girl with idiopathic sexual precocity (30 days). Additionally pregnanediol-3-glucuronide (PG) excretion was determined in the urines of the adult female. Gonadotropin and PG excretion patterns of the adult female were those associated with a normal menstrual cycle. Excretion of melatonin, mean +/- SD, (11.3 +/- 2.7 vs 4.7 +/- 1.4 ng/h, p less than 0.005) was greater and PG (38.3 +/- 81 vs 124.2 +/- 46.7 ug/h, p less than 0.005) was less during the first 13 days as compared to the subsequent 14 days. Gonadotropin and melatonin excretions correlated positively (first 13 days FSH, r = 0.828; rs = 0.815 and LH, r = 0.816; rs = 0.905, p less than 0.005 and subsequent 14 days FSH, r = 0.607; rs = 0.685, p less than 0.025 and LH, r = 0.490, p less than 0.05; rs = 0.638, p less than 0.025). Excretion of PG and melatonin did not correlate during the first 13 days. However, during the subsequent 14 days they correlated negatively (r = -0.679, p less than 0.005; rs = -0.620, p less than 0.025). During the 28-day period the gonadotropin and melatonin excretion patterns of the 11-year-old girl showed random fluctuations and correlated positively (FSH, r = 0.669; rs = 0.631 and LH, r = 0.690; rs = 0.695, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary steroid evaluations to monitor ovarian function in exotic ungulates: II. Comparison between the giraffe (Giraffa camelopardalis) and the Okapi (Okapia johnstoni)

AbstractOvarian activity in the female giraffe was evaluated during the nonfertile ovarian cycle and during the terminal stages of gestation. Progesterone metabolites, in the form of pregnanediol‐3‐glucuronide (PdG), were measured in daily random urine samples collected from four adult parous giraffes. The follicular phase averaged 4.0 ± 0.1 days in length (N = 12; range 3–5 days) and peak PdG levels in the postovulatory period averaged 30.9 ± 1.7 ng/mg Cr (N = 12). PdG levels during the latter half of gestation greatly exceeded average luteal phase levels, which is in contrast to domestic ruminants. Prior to parturition, a marked decline in PdG excretion was evident, which may be useful for anticipating this event. These data serve to elucidate ovarian function in the mature female giraffe and to provide information concerning the physiologic role of certain anomalous ovarian structures. In addition, observed similarities in the pattern of PdG excretion during the nonfertile cycles of the giraffe and the okapi indicate similar underlying physiologic processes.

INDICINE--HORMONAL BIRTH CONTROL ON A NATURAL BASIS.

Summary. A 'normally' functioning corpus luteum assures sterility in women; progesterone-deficiency is associated with the occurrence of premenstrual secondary ovulations, which may result in pregnancy. Trials involving 342 women during 2371 menstrual cycles and 14,947 pregnanediol determinations showed that the presence of a 'normally' functioning corpus luteum is indicated by an average daily pregnanediol glucuronide elimination of at least 3·5 mg. The 'safe period' is unreliable unless the production of progesterone by the corpus luteum of ovulation is maintained above the level indicated by the excretion of pregnanediol glucuronide at this rate. 'Indicine' provides a readily applied method of determining whether the pregnanediol excretion rate is above this level.