Baseline Progesterone Research Articles

Cyclic estrous-like behavior in a spayed cat associated with excessive sex-hormone production by an adrenocortical carcinoma

A 15-year-old, spayed female domestic shorthair cat was evaluated for 1-year duration of cyclic intermittent estrous behavior. Diagnostic testing performed before referral, including baseline progesterone concentration, human chorionic gonadotropin (hCG) hormone stimulation test and surgical exploratory laparotomy, had remained inconclusive for a remnant ovary. Evaluation of sex hormones before and after adrenocorticotropic hormone (ACTH) administration revealed increased basal concentrations of androstenedione, estradiol, progesterone, and 17α-hydroxyprogesterone and normal ACTH-stimulated hormone concentrations. Enlargement of the right adrenal gland was identified by abdominal ultrasound. The cat underwent an adrenalectomy and histopathology of the excised adrenal gland was consistent with an adrenocortical carcinoma. Clinical signs resolved immediately following surgery, and most hormone concentrations declined to within or below the reference interval (RI) by 2 months after surgery.

Seasonal changes in ovarian steroid hormone concentrations in the large hairy armadillo (Chaetophractus villosus) and the crying armadillo (Chaetophractus vellerosus)

Knowledge of armadillo reproductive physiology is essential for developing ex situ and in situ assisted reproductive techniques for propagating and/or controlling populations of these animals. The present study included assessment of fecal sex steroids by radioimmunoassay, determining reproductive status via monitoring ovarian activity (in the wild) and therefore reproductive status, in wild females of the large hairy armadillo (Chaetophractus villosus) and the crying armadillo (Chaetophractus vellerosus) in the southern hemisphere. Plasma and fresh fecal progesterone concentrations were not significantly correlated in either species. However, in both species, there was a significant positive correlation between plasma progesterone and dry fecal progesterone concentrations (r = 0.82, P < 0.05 and r = 0.60, P < 0.05, respectively). Dry fecal progesterone and estradiol concentrations were measured in one captive C. villosus (average baseline progesterone and estradiol concentrations 28.72 ± 11.75 ng/g dry feces and 3.04 ± 0.80 ng/g dry feces, respectively) and one captive C. vellerosus (average baseline progesterone and estradiol concentrations 14.05 ± 3.03 ng/g dry feces and 3.46 ± 1.20 ng/g dry feces, respectively) to detect hormonal peaks over 1 y; these occurred from late fall to early summer. Feces from wild C. villosus and C. vellerosus were also collected over 1 y to determine progesterone peaks, which occurred in winter and spring in both species (with no peaks during the summer or fall). Accordingly, C. villosus and C. vellerosus had a seasonal reproductive pattern. The significant correlations between dry fecal and plasma progesterone concentrations validated this method for monitoring reproductive status in these species.

Transdermal Delivery of Bioidentical Progesterone with a Steroid 5α-Reductase Inhibitor (Dutasteride): a Pilot Study

Bioavailability of transdermal progesterone is low and variable. This may be attributed to transdermal metabolism by the 5α-reductase enzymes or the direct transport to the saliva. The objective of the current study was to evaluate the effect of enzyme inhibition on the bioavailability of transdermal progesterone. Serum and salivary progesterone levels were evaluated to gain a better insight into the mechanism progesterone transport across the skin. Twenty postmenopausal women with a Follicle Stimulating Hormone > 40IU/L were recruited to take part in the study. The subjects were randomly allocated to either dutasteride (n=10) or placebo (n=10). Each group applied either 500 mg of non ionic cream or dutasteride cream (2mg/g) to the right arm for 2 weeks. This was followed by applying 500 mg of progesterone or progesterone dutasteride cream (equivalent to 40 mg of progesterone) for a further 2 weeks. On day 30 blood and saliva were collected for over 12 hours and progesterone concentration was measured. The baseline progesterone concentration on day zero was 0.1 ng/ml. On day 30 baseline progesterone levels increased significantly (p <0.05) to 1.40 ng/ml and 1.15 ng/ml in the progesterone and dutasteride groups, respectively. Salivary progesterone concentrations were increased by seven fold, from 0.40 ng/ml to 2.9 ng/ml. On average, salivary progesterone concentration was four times the serum levels. The average serum and salivary progesterone concentration, Cmax, and the AUC were slightly higher in the dutasteride group, but no significant difference could be noted. Metabolism by the 5α-reductase enzyme is unlikely to affect the bioavailability of progesterone.

Methods of estrus detection and correlates of the reproductive cycle in the sun bear ( Helarctos malayanus)

The objective was to explore multiple methods for detecting and characterizing the reproductive cycle of the sun bear ( Helarctos malayanus). Thirteen H. m. euryspilus females, loaned from the Malaysian government to US zoos, were used. Fecal metabolite concentrations of estrogen and progesterone were compared to vaginal cytology, changes in genital appearance, and behavior (videotapes and zookeeper observations). Cytology and video behavior were characterized during five hormonally defined states: high, low, and baseline progesterone, estrus, and high estrogen. Among states, there were significant differences in cytology and behavior. Sexual, affiliative, and stereotypic behaviors were highest during estrus, whereas affiliative and social behaviors were lowest during high progesterone. In this captive breeding population, 30.8% of females cycled two or three times a year, 30.8% cycled once a year, and 38.5% did not cycle during this study. Inter-estrus intervals were (mean ± SEM) 115.7 ± 6.3 d (range, 101–131). Spearman rank correlations were significant between both ordinal sexual and affiliative behaviors and vulva swelling and color. Sexual behavior was significantly positively correlated with superficial and keratinized cells, but negatively correlated with parabasal and basophilic cells in cycling females (opposite pattern for appetitive behavior). In conclusion, data for cytology, vulva changes and behavior were consistent with, and complementary to, hormonal data; collectively, they delineated estrus and identified specific reproductive types.

Childhood Conditions Influence Adult Progesterone Levels

BackgroundAverage profiles of salivary progesterone in women vary significantly at the inter- and intrapopulation level as a function of age and acute energetic conditions related to energy intake, energy expenditure, or a combination of both. In addition to acute stressors, baseline progesterone levels differ among populations. The causes of such chronic differences are not well understood, but it has been hypothesised that they may result from varying tempos of growth and maturation and, by implication, from diverse environmental conditions encountered during childhood and adolescence.Methods and FindingsTo test this hypothesis, we conducted a migrant study among first- and second-generation Bangladeshi women aged 19–39 who migrated to London, UK at different points in the life-course, women still resident in Bangladesh, and women of European descent living in neighbourhoods similar to those of the migrants in London (total n = 227). Data collected included saliva samples for radioimmunoassay of progesterone, anthropometrics, and information from questionnaires on diet, lifestyle, and health. Results from multiple linear regression, controlled for anthropometric and reproductive variables, show that women who spend their childhood in conditions of low energy expenditure, stable energy intake, good sanitation, low immune challenges, and good health care in the UK have up to 103% higher levels of salivary progesterone and an earlier maturation than women who develop in less optimal conditions in Sylhet, Bangladesh (F 9,178 = 5.05, p < 0.001, standard error of the mean = 0.32; adjusted R 2 = 0.16). Our results point to the period prior to puberty as a sensitive phase when changes in environmental conditions positively impact developmental tempos such as menarcheal age (F 2,81 = 3.21, p = 0.03) and patterns of ovarian function as measured using salivary progesterone (F 2,81 = 3.14, p = 0.04).ConclusionsThis research demonstrates that human females use an extended period of the life cycle prior to reproductive maturation to monitor their environment and to modulate reproductive steroid levels in accordance with projected conditions they might encounter as adults. Given the prolonged investment of human pregnancy and lactation, such plasticity (extending beyond any intrauterine programming) enables a more flexible and finely tuned adjustment to the potential constraints or opportunities of the later adult environment. This research is the first, to our knowledge, to demonstrate a postuterine developmental component to variation in reproductive steroid levels in women.

Effect of new and reused CIDRs on serum progesterone concentrations in lactating dairy cows

Despite the common practice of re-using a popular intravaginal progesterone releasing device by United States cattle producers, there is little published scientific evidence whether this practice is effective as an aid in synchronizing oestrus. The study was conducted to determine the effect of new and reused CIDRs containing 1.38 g progesterone on the serum progesterone concentrations in cows that received the same CIDR twice in succession. 40 cows were divided into three treatments as T1 (n=18), T2 (n=15) and T3 (n=7). Prior to the start of each trial, 5.0 ml dinoprost was injected to each cow, then serum samples were collected for progesterone measurement on the same day. Results revealed that 37 samples had serum progesterone concentrations of &gt;1.1 ng/ml and the average serum progesterone concentrations of T1, T2 and T3 were 2.7243, 4.0973 and 2.7027, respectively. It was observed that the mean serum progesterone concentrations on days 2 and 3, days 5 and 6 and days 8 and 9 were significantly different and varied between trials. Serum progesterone concentrations associated with used CIDRs were statistically similar to baseline progesterone concentrations obtained from cows before new CIDR insertion. It is suggested that there is either significant loss of progesterone in the CIDR insert after one use or decrease absorption of progesterone available from the used CIDRs, and the reuse of 1.38 g CIDRs to aid in synchronization of oestrus in lactating dairy cattle is not recommended.

Priming with progestin, but not GnRH antagonist, induces a consistent endocrine response to exogenous gonadotropins in induced and spontaneously ovulating cats

Ovarian sensitivity to exogenous gonadotropin stimulation (equine chorionic gonadotropin [eCG] and human chorionic gonadotropin [hCG]) following pre-treatment with a progestin (levonorgestrel) versus GnRH antagonist (antide) was studied in cats known to be induced versus spontaneous ovulators. Queens were assigned to one of three treatments: (1) levonorgestrel implants + eCG/hCG ( n = 7 cats); (2) antide injections + eCG/hCG ( n = 7) or (3) eCG/hCG alone (control; n = 7). Hormonal metabolites were assessed in fecal samples collected daily for 60 days before and during the 37 days inhibitory pre-treatment and for more than 60 days after eCG/hCG. Fecal metabolites of estradiol and progesterone were measured by radioimmunoassay. Females that maintained baseline progesterone were considered induced ovulators, whereas cats that exhibited a luteal phase before inhibition treatment were classified as spontaneous ovulators. Based on fecal hormone profiles, levonorgestrel thoroughly inhibited ovarian activity, whereas antide synchronized follicular phases but did not induce complete ovarian down-regulation. Both treatments prevented ovulation in spontaneous ovulators, but neither caused regression of existing corpora lutea (CL). Levonorgestrel, but not antide, pre-treatment resulted in a quiescent ovary at the time of eCG injection, yet endocrine responses to eCG/hCG were not different among treatments. Interestingly, spontaneously ovulating females exhibited a prolonged estradiol response to gonadotropin stimulation compared to induced ovulators, and this prolonged estradiol surge was replicated by levonorgestrel pre-treatment. Thus, the progestin levonorgestrel effectively suppresses follicular and luteal activity in the cat, resulting in a more consistent response to gonadotropin stimulation, even in females prone to spontaneous ovulation.

Introduction of bulls at different days postpartum on resumption of ovarian cycling activity in primiparous beef cows1

The objective of this study was to evaluate postpartum resumption of ovulatory cycles among primiparous, suckled beef cows that were exposed continuously to mature bulls beginning at various intervals after calving. We sought to determine whether cumulative distributions of proportions of cows resuming ovarian cycles and interval from the start of bull exposure to resumption of ovarian cycling activity differed among cows exposed continuously (BE) or not exposed (NE) to bulls beginning on d 15, 35, or 55 after calving. Angus x Hereford cows (n = 56) were assigned randomly to one of six treatments in a 2 (exposure type) x 3 (day exposed postpartum) factorial arrangement. Blood samples were collected from each cow starting on d -1, and every third day until the end of experiment. An increase in baseline progesterone concentrations that exceeded 1.0 ng/mL in three consecutive samples was used as evidence of resumption of ovarian cycling activity. More (P < 0.05) BE cows resumed cycling activity by the end of the experiment than NE cows. Proportions of cows resuming cycling activity did not differ (P = 0.30) among cows exposed to bulls on d 15, 35, or 55 postpartum. Proportions of BE cows that were exposed to bulls on d 15, 35, or 55 were greater for each 10-d interval (P < 0.05) than those for NE cows during the first 40 d after exposure. More (P < 0.05) BE cows exposed to bulls on d 55 resumed cycling activity by 30 d after exposure than BE cows exposed to bulls on either d 15 or 35. Interval from calving to resumption of cycling activity was decreased (P < 0.05) by the presence of bulls. Day of exposure did not affect (P = 0.21) interval from calving to resumption of cycling activity; however, interval from day of bull exposure to resumption of cycling activity decreased (P < 0.05) linearly as day of exposure to bulls after calving increased. We conclude that exposing primiparous beef cows to bulls decreased the postpartum anovulatory interval and increased the proportion of cows that exhibit resumption of ovarian cycling activity, independent of day of bull exposure. Furthermore, cows exposed to bulls at progressively later intervals postpartum seemed to respond more rapidly to the biostimulatory effect of bulls than when they were exposed earlier in the postpartum anestrous period.

Retrospective evaluation of steroid hormone intermediates in dogs with alopecia

The purpose of this study was to determine if there are specific steroid hormonal aberrations associated with suspect endocrine alopecias in dogs where hypothyroidism and hyperadrenocorticism have been excluded. Steroid hormone panels submitted to the UTCVM endocrinology laboratory over a 7.5‐year period (783 samples) from dogs with alopecia were reviewed. To be included in the final analysis, complete information about age, sex, neuter status and breed was required; hypothyroidism had been ruled out; and cortisol concentration post‐ACTH stimulation was less than 200 ng mL−1. A total of 276 dogs met the criteria for inclusion (seven intact females, 32 intact males, 134 spayed females, 103 neutered males) and comprised of 54 different breeds. Approximately 73% of dogs had at least one steroid hormone intermediate greater than the normal range. The most frequent hormone elevation was noted in baseline and/or post‐ACTH stimulation progesterone (57.9% of samples). Breeds that contained seven or more dogs were statistically compared. Only malamute dogs failed to show an increase in progesterone for any dog. When compared with normal dogs, oestradiol was significantly greater in keeshond dogs and baseline progesterone was significantly greater in pomeranians and husky breed dogs. While significant difference existed among breeds, neither baseline nor post‐stimulation 17‐hydroxyprogesterone differed significantly from normal values. Chow‐chow and malamute dogs had the greatest percentage of dogs with completely normal steroid hormone intermediates. Results of this study suggest that the pathomechanism of the alopecia, at least for some breeds, may not relate to steroid hormone intermediates. Funded by the Companion Animal Fund, Department of Small Animal Clinical Sciences.

Alterations in ovarian follicular progesterone secretion by elevated exposures to the drinking water disinfection by-product dibromoacetic acid: examination of the potential site(s) of impact along the steroidogenic pathway

Previous data from our laboratory indicated that the drinking water disinfection by-product, dibromoacetic acid (DBA), when applied in vitro to rat preovulatory follicles at a concentration consistent with blood levels found to disrupt estrous cyclicity, was able to block the stimulated secretion of progesterone. The present experiments focused on establishing a dose–response for such an effect and identifying the point(s)of impact of this compound along the steroidogenic pathway that underlie this suppression. Immature Sprague–Dawley rats were primed with PMSG on day 26 and killed 48 h later. Preovulatory follicles were removed and paired in culture with or without DBA (2–50 μg/ml) to reassess progesterone secretion under hCG-stimulated or baseline conditions. In addition, media supplemented with pregnenolone or 22( R)-hydroxycholesterol (22 R-HC) were used to determine the effects of 50 μg/ml DBA on the initial steps leading to progesterone synthesis. Samples taken over the course of 24 h reaffirmed a significant DBA-associated suppression in baseline and stimulated progesterone release, while estradiol secretion was unaffected. This effect was mirrored by a reduction in follicular progesterone content in these DBA groups. The addition of pregnenolone eliminated this decrease, with the DBA-exposed follicles exhibiting a linear increase in progesterone release over the sampling period. The follicular progesterone content at 24 h showed that DBA treatment under pregnenolone supplementation caused marked elevations under both the hCG stimulated and non-stimulated conditions, something not reflected in the release data. Substitution of 22 R-HC for pregnenolone eliminated the effect on baseline progesterone release, although the attenuation in stimulated secretion was still present. This suggests both an effect of DBA exposure on mitochondrial cholesterol transport by steroidogenic acute regulatory protein (StAR) and a possible impact on the receptor or postreceptor events triggered by hCG.

Preimplantation urinary hormone profiles and the probability of conception in healthy women

Objective: To examine hormonal predictors of conception in menstrual cycles from normal women. Design: Longitudinal study. Setting: Community. Patient(s): Two hundred fifteen healthy female volunteers with no known fertility problems who were trying to conceive. Intervention(s): Participants recorded menstrual bleeding, sexual intercourse, and collected first morning urine specimens daily from when they stopped contraception until they became pregnant or for 6 months if no clinical pregnancy was achieved. Measurements were made of urinary LH and urinary metabolites of estrogen and progesterone. Main Outcome Measure(s): Conception was identified by a sensitive and specific immunoradiometric assay for urinary hCG. Result(s): Statistical analyses of 189 conception and 409 nonconception cycles controlled for sexual intercourse and interdependence of cycles from the same woman. Conception was more likely in cycles with lower baseline progesterone metabolite levels, higher ovulatory LH, and higher midluteal progesterone. Midluteal estrogen also was elevated in conception cycles when examined without adjusting for other hormone levels, but this finding did not persist after multivariate adjustment. Conclusions: Menstrual cycles in normal women vary in their hormonal quality in ways that are predictive of cycle fertility.

Serum concentrations of oestradiol and progesterone, and sexual behaviour during the normal oestrous cycle in the leopard (Panthera pardus).

Three mature nulliparous female leopards were studied for 5 years. During three separate 6-month periods serum oestradiol and progesterone concentrations were measured at weekly intervals. Oestradiol was elevated over 21 pg/ml for 54 weeks during these 3 periods, and 36 oestradiol peaks (65.8 +/- 6.3 pg/ml (mean +/- s.e.m.), range 21-172 pg/ml) were identified. Daily frequency of feline reproductive behaviours averaged over each week increased from 1.9 +/- 0.2 (n = 93) during weeks with low serum oestradiol concentrations (less than 21 pg/ml) to 5.3 +/- 0.6 (n = 54) during weeks when serum oestradiol concentrations (greater than 21 pg/ml) were high. Increased serum progesterone concentrations (13-98 n/gml) were observed on 5 occasions in 2 leopards housed together. These presumptive luteal phases lasted from 1 to 5 weeks. Baseline progesterone values were 1.6 +/- 0.4 ng/ml (n = 131). No progesterone increments were observed in isolated animals, and serum concentrations remained at baseline levels. These limited observations suggest that female leopards do not require intromission to induce ovulation and luteal function. The average interval between oestradiol peaks for cycles with no progesterone increment was 3.4 weeks (range 1-6 weeks). The interval for the 3 complete cycles associated with elevated progesterone concentrations was 7.3 weeks. Analysis of sexual behaviours over the 5-year study period revealed no evidence of seasonality in these captive leopards.

Low-dose prostaglandin E2 analogue for cervical dilatation prior to pregnancy termination

The trauma of mechanical cervical dilatation preceding abortion is directly related to the degree of cervical resistance. Prostaglandins may reduce cervical rigidity but are accompanied by undesirable side effects. Our aims were to ascertain if a low-dose (10 mg) analogue (9-deoxo-16, 16 dimethyl-9-methylene PGE2) is effective and well tolerated and, if so, to try to determine the possible mechanism by which it works. To this end, we studied 39 women with gestational ages ranging from 7 to 19 weeks who were given a single vaginal suppository 1 to 4 hours before suction curettage. In addition to demographic data on age, gravidity, parity, and previous abortions, we determined progesterone, human chorionic gonadotropin and prostaglandin plasma levels. This low-dose prostaglandin E2 analogue was found to be effective in achieving cervical dilatation and softening with minimal side effects (mild nausea in one patient only). Mean cervical dilatation achieved was 7.8 +/- 2.3 mm. Softening was apparent and facilitated additional instrumental dilatation when required. No correlation was found between drug effectiveness and gravidity, gestational age, or duration of action. There was no detectable trend with regard to baseline progesterone or human chorionic gonadotropin levels. This suggested a specific sensitivity to the local effect by the drug, apparently unrelated to dosage.

Evaluation of clinical and luteolytic effects of a novel prostaglandin analogue in normal and problem mares.

Alfaprostal (K 11941), a novel prostaglandin F2 alpha analogue was clinically tested in 24 dioestrous mares, 40 anoestrous mares and 31 postpartum mares, all being given 2 or 3 mg intramuscularly. Blood samples were taken for the determination of plasma progesterone levels and the objective confirmation of luteolytic drug effects. Two hundred and thirty-six mares at the same location were used for comparisons of the rates of pregnancy, early embryonic loss and foaling. Alfaprostol was found to act as a potent luteolytic agent with good oestrus induction, follicular development and normal conception (72.6%) and foaling rate (65.3%). No side effects were observed. Treatments commenced early in the season (October), when only 35% of the anoestrous mares showed elevated progesterone levels, but in 80% of anoestrous mares with baseline progesterone levels, alfaprostol initiated heat and ovulation followed by normal fertility.

Effectiveness of a novel prostaglandin analog in postpartum mares and mares with early season anestrus

Contents Fifty thoroughbred mares, located at Central-Southern Brazil near Sao Paulo (13 anestrous maiden, 18 anestrous barren mares and 19 postpartum mares) were treated with one to three injections, 48 hrs apart, of 2 mg of the novel PGF analog K 11941*, during the early part of the breeding season. Early season anestrus in these problem mares was compounded by the adverse effects of a drought. Plasma progesterone determinations revealed unexpectedly elevated plasma progesterone levels in 61.5% of the maiden mares, in 77.8% of the barren mares and in 68.4% of the postpartum mares (20 to 25 days postpartum). Treatments with K 11941 initiated luteolysis, heat and ovulations in 91.4, 45.5 an 63.3% of these mares, respectively, but initiated also heat and ovulation in 13% and 33% of mares with baseline progesterone levels. Treatments initiated covert and overt cyclic functions in 17 and 12 of those animals which did not conceive immediately. Fifteen animals with recurrent anestrus received further treatment with K 11941. Ten mares cycling silently were force bred when palpations indicated ovulatory follicles, and 7 conceived. Of the 50 mares treated, 38 became pregnant (76%: maiden mares: 76.9%; barren mares: 77.8% and postpartum mares: 73.7%) with breeding indices of 1.9, 1.36 und 1.57, respectively; and 37 mares gave birth to a live foal (74%), At the same stud, 138 control mares had a foaling rate of 82.6%.

Prolactin synthesis and release during pregnancy and puerperium

Prolactin (PRL) synthesis and its release following thyrotropin-releasing hormone (TRH) administration during pregnancy and puerperium was studied in 45 women. Mean baseline E2 increased from 1,900 ± 384 (SEM) pg/ml in the first trimester to 3,520 ± 849 in the second trimester (P < 0.05) and 43,057 ± 5,765 pg/ml in the third trimester (P < 0.001) of pregnancy. Mean baseline progesterone increased from 27.6 ± 3.2 ng/ml in the first trimester to 41.9 ± 6.6 in the second trimester (P < 0.01) and 109.3 ± 11.2 ng/ml in the third trimester (P < 0.001) of pregnancy. Ten days after delivery, mean E2 dropped to 13 ± 2.9 pg/ml and progesterone dropped to 0.56 ± 0.07 ng/ml in the lactating women; in the nonlactating women, mean E2 level was 100 ± 44 pg/ml and mean progesterone was 0.63 ± 0.09 ng/ml. Baseline PRL increased from 27 ± 4.0 ng/ml in the first trimester to 67 ± 10 ng/ml in the second trimester (P < 0.003) and to 157 ± 15 ng/ml in the third trimester (P < 0.002). The increased synthesis of PRL with increasing gestation was thought to be due to the stimulatory effects of E2 and progesterone, resulting in hyperplasia of the lactotrophs. In response to TRH, PRL demonstrated a significant increase from the first trimester to the second, with no further increase in the third. Therefore, it appears that the PRL reserve increases only during the first and second trimesters of pregnancy. Ten days after delivery, baseline PRL in response to TRH decreased to levels found in the first and second trimesters. However, the lactating women released less PRL than the nonlactating subjects (P < 0.01), since PRL is released with each lactating episode which in turn probably reduces the PRL reserve.