Reproductive Hormone Use Research Articles

The economic effect of cow-based reproductive management programs with a systematic use of reproductive hormones

Hormone-based reproductive management programs can be beneficial to improve dairy cow's reproductive performance. This study aimed to compare the economic impact of reproductive management programs using systematic hormonal treatments to individual cows with a specific DIM range with a reproductive management program using cow-specific hormonal treatment based on a veterinary diagnosis of ovarian dysfunction during a fertility check. An existing individual cow-based, dynamic, and stochastic bio-economic simulation model, mimicking the production dynamics of a 200 cow-herd in daily time steps, was extended with ovarian dysfunction and fertility inputs. Four hormone-based reproductive management programs were modeled. In the default reproductive management program, reflecting the current reproductive management of Dutch herds, lactating dairy cows are inseminated based on detection of estrus and non-cyclic dairy cows are treated with hormones based on a veterinary diagnosis of ovarian dysfunction during a fertility check. Hormone treatments prescribed by the veterinarian for anestrus, cystic, and sub-estrus cows were an 8-d progesterone-releasing intravaginal device (PRID)-Synch protocol (PRIDsynch), an Ovsynch protocol, and a PGF2⍺ treatment, respectively. The 3 other reproductive management programs reflected systematic hormonal treatments to cows at specific DIM and included a 1) Double-Ovsynch protocol for TAI with nonpregnant cows submitted to a resynchronization protocol (FTAI), 2) Double-Ovsynch protocol for TAI with nonpregnant cows detected in estrus or submitted to a resynchronization protocol (FTAI+ED), and 3) detection of estrus with cows not detected submitted to a PRIDsynch protocol (ED+TAI). All nonpregnant cows were submitted to a resynchronization protocol based on the absence (PRIDsynch) or presence (Ovsynch protocol) of a corpus luteum (CL). The annual mean net economic return (NER) was calculated for all reproductive management programs. Compared with the default reproductive management program, the highest NER was observed for the FTAI+ED reproductive management program with €23,764 higher net revenues, followed by the FTAI and the ED+TAI reproductive management programs with €19,550 and €14,314 higher net revenues, respectively. Overall, systematic hormone-based reproductive management programs gave higher costs due to more hormones administered and higher calving and feed costs due to more pregnant cows. Nevertheless, the additional revenues of milk and calves in the systematic hormone-based reproductive management programs outweighed the total cost. For instance, the FTAI+ED reproductive management program gave €8,953 higher total cost per year compared with the default but with €32,654 higher revenues. In summary, reproductive management programs where hormones were systematically used gave economic advantages over the current default reproductive management program in which hormones are administered to individual cows based on a veterinary diagnosis of ovarian dysfunction during a fertility check.

Influence of repeated estrus synchronization treatment on hormone secretion, growth, and development of dairy goats.

In large-scale intensive farms, dairy goats often undergo frequent estrus synchronization (ES) treatment, which may result in a decline in reproductive performance; however, the underlying mechanism remains unclear. The present study aimed to investigate the effect of pregnant mare serum gonadotropin (PMSG) and progesterone (P4)-mediated ES treatment on fertility in dairy goats, while also identifying key metabolic and endocrine mechanisms that influence reproductive performance in does subjected to repeated ES treatment. Forty-eight Saanen does were randomly assigned to two groups (24 goats each) that received ES treatments either thrice fortnightly (3-PMSG) or once (1-PMSG) simultaneously with the third ES treatment of the 3-PMSG group during the breeding season. ES treatment was performed via the intravaginal insertion of a controlled internal drug release (CIDR) device impregnated with 300 mg P4, followed by 300 IU PMSG injections 48 h before CIDR withdrawal. Blood was collected to detect the level of hormones and blood biochemical indices. Additionally, estrus rate, fecundity rate, body weight, size, and lactation performance were measured. The results showed that repeated ES treatment markedly decreased the estrus rate and fecundity rate of goats. Among the does in all groups, there was no substantial difference in follicle stimulating hormone, luteinising hormone, gonadotropin-releasing hormone, melatonin, growth hormone, PMSG, total cholesterol, total protein, and glucose levels, as well as the body weight, body size, and lactation performance. Repeated ES treatment elevated estrogen (E2) levels 36, 48, and 72 h post-CIDR removal; increased P4 upon CIDR insertion; and raised PMSG antibody levels 24, 48, and 72 h post-CIDR removal. The results suggest that elevated anti-PMSG levels are the primary reason for the decline in ES efficiency, and that high E2 and P4 levels at some time points also impair reproductive performance. These findings provide novel insights into the metabolic effects of repeated PMSG stimulation in goats, guiding future reproductive hormone use in breeding practices.

THU642 Progression To Cirrhosis And All-cause Mortality Are Increased In Postmenopausal Women With NAFLD

Abstract Disclosure: C. Izzi-Engbeaya: None. P. Eng: None. A. Dunin-Borkowska: None. R. Forlano: None. B.H. Mullish: None. G. Sigon: None. V. Lin: None. T. Tan: None. M. Yee: None. P. Manousou: None. W.S. Dhillo: None. Background: Up to 30% of adults worldwide are estimated to have Non-alcoholic Liver Disease (NAFLD), ranging from hepatic steatosis alone to steatohepatitis and cirrhosis. Due to underlying metabolic and hepatic pathology, patients with NAFLD require specialist input from Endocrinologists and Hepatologists. Worryingly, postmenopausal women with NAFLD are more likely to progress to advanced fibrosis and experience more frequent liver decompensation events than men, but the causes of these disparate outcomes are incompletely understood. Methodology: We performed a retrospective cohort study utilising a database of consecutive patients managed in the multidisciplinary Metabolic Endocrinology and Hepatology Clinic at Imperial College Healthcare NHS Trust (London, UK) who had their first clinic review between January 2009 and December 2020. NAFLD was diagnosed clinically or histologically. Clinical, biochemical and histological data were collected up to December 2022. Postmenopausal women were defined as women aged ≥55 years at their initial clinic visit. Cirrhosis was diagnosed based on a combination of clinical and radiological features or based on histology, when available. Multivariate logistic regression was performed to identify variables independently associated with cirrhosis. Statistical significance was set at p<0.05. Results: 739 patients were included in this study (n=286 female, n=244 White, median (IQR) age: 52 (42-60) years), with a median follow-up of 6 (3-8) years. All-cause mortality was highest amongst postmenopausal women (proportion who died during follow-up: men <55y 2% vs men ≥55y 9% vs women <55y 0.8% vs women ≥55y 14%, p<0.0001). Postmenopausal women (n=153) had increased risks of cirrhosis when compared to age-matched men (cirrhosis: OR 2.8 (95%CI 1.1-7.2), p<0.05). Postmenopausal women had lower ALT levels at initial clinic review (median (IQR) ALT IU/L: women ≥55y 48 (30-73) vs men ≥55y 54 (41-77), p <0.05), and lower alcohol intake than age-matched men (p<0.0001). Similar proportions of postmenopausal women and age-matched men had a baseline fibrosis stage ≥2 (82% vs 78% respectively, p=0.55). Initial prevalence of obesity (p=0.63), type 2 diabetes (p=0.15), cardiovascular disease (p=0.21), as well as use of GLP-1 receptor agonists (p=0.17) and SGLT2 inhibitors (p>0.99) were similar between these two groups. There were insufficient data on reproductive hormone use for this variable to be included in the analyses. Conclusions: Despite presenting to a specialised secondary care clinic with similar co-morbidities, liver fibrosis stage, and receiving similar treatments, being a postmenopausal woman in our diverse cohort is associated with worse outcomes than being a man aged ≥55years. Therefore, tailored and/or personalised management strategies may be required to improve outcomes in postmenopausal women with NAFLD. Presentation: Thursday, June 15, 2023

Targeted reproductive management for lactating Holstein cows: Reducing the reliance on exogenous reproductive hormones

Adoption of automated monitoring devices (AMD) affords the opportunity to tailor reproductive management according to the cow's needs. We hypothesized that a targeted reproductive management (TRM) would reduce the use of reproductive hormones while increasing the percentage of cows pregnant 305 d in milk (DIM). Holstein cows from 2 herds (n = 1,930) were fitted with an AMD at 251.0 ± 0.4 d of gestation. Early-postpartum estrus characteristics (EPEC; intense estrus = heat index ≥70; 0 = minimum, 100 = maximum) of multiparous cows were evaluated at 40 (herd 1) or 41 (herd 2) DIM and EPEC of primiparous cows were evaluated at 54 (herd 1) or 55 (herd 2) DIM. Control cows received the first artificial insemination at fixed time (TAI; primiparous, herd 1 = 82 and herd 2 = 83 DIM; multiparous, herd 1 = 68 and herd 2 = 69 DIM) following the Double-Ovsynch (DOV) protocol. Cows enrolled in the TRM treatment were managed as follows: (1) cows with at least one intense estrus were inseminated upon AMD detected estrus for 42 d and, if not inseminated, were enrolled in the DOV protocol; and (2) cows without an intense estrus were enrolled in the DOV protocol at the same time as cows in the control treatment. Control cows were re-inseminated based on visual or patch aided detection of estrus, whereas TRM cows were re-inseminated as described for control cows with the aid of the AMD. Cows received a GnRH injection 27 ± 3 d after insemination and, if diagnosed as nonpregnant, completed the 5-d Cosynch protocol and received TAI 35 ± 3 d after insemination. Among cows in the TRM treatment, 55.8 and 42.9% of primiparous and multiparous cows, respectively, received the first insemination in spontaneous estrus. The interaction between treatment and parity affected pregnancy 67 d after the first AI (primiparous: control = 37.6%, TRM = 27.4%; multiparous: control = 41.0%, TRM = 44.7%). The TRM treatment increased re-insemination in estrus (control = 48.3%, TRM = 70.5%). Pregnancy 67 d after re-inseminations tended to be affected by the interaction between treatment and EPEC (no intense estrus: control = 25.3%, TRM = 32.0%; intense estrus: control = 32.9%, TRM = 32.2%). The interaction between treatment and EPEC affected pregnancy by 305 DIM (no intense estrus: control = 80.8%, TRM = 88.2%; intense estrus: control = 87.1%, TRM = 86.1%). Treatment did not affect the number of reproductive hormone treatments among cows that had not had an intense estrus (control = 10.5 ± 0.3, TRM = 9.1 ± 0.2 treatments/cow), but cows in the TRM treatment that had an intense estrus received fewer reproductive hormone treatments than cows in the control treatment (2.0 ± 0.1 vs. 9.6 ± 0.2 treatments/cow). Selecting multiparous cows for first AI in estrus based on EPEC reduced the use of reproductive hormones without impairing the likelihood of pregnancy to first AI. The use of AMD for re-insemination expedited the establishment of pregnancy among cows that did not display an intense estrus early postpartum.

Role of aquaporin 3 in reproductive performance of dairy goats after repeated estrus synchronization stimulation.

This study explored the specific molecular mechanisms through which repeated estrus synchronization (ES) treatments reduce the reproductive performance of dairy goats. Ninety-six goats (n=24/group) were randomly assigned to two groups receiving ES treatments thrice every fortnight (3- equine chorionic gonadotropin [eCG] and 3-follicle stimulating hormone [FSH] groups) and two groups receiving one ES treatment (1-eCG and 1-FSH groups). ES treatments of 1- and 3-eCG goats were performed via the intravaginal insertion of a controlled internal drug release (CIDR) device containing 300 mg progesterone (P4), followed by 300 IU eCG injections 48 h before CIDR withdrawal. The 1- and 3-FSH goats received CIDR for 10 d, followed by 50 IU FSH and 100 μg PGF2α within 12 h of CIDR withdrawal. Ovaries of three goats in estrus from both groups were harvested for analysis. Subsequently, all the goats in estrus were artificially inseminated twice. Consequently, 3-eCG and 3-FSH goats showed a considerably reduced estrus rate and litter size than 1-eCG and 1-FSH goats. AQP3 mRNA and protein expression were significantly higher in the 3-eCG and 3-FSH groups than in the 1-eCG and 1-FSH groups. AQP3 overexpression led to cell apoptosis and decreased steroid hormone secretion ability of ovarian granulosa cells. Moreover, it resulted in a decrease in maturation and cleavage rates after parthenogenetic activation and in vitro fertilization, respectively. AQP3 gene was involved in reducing the reproductive performance of repeated ES-treated dairy goats. These findings provide a theoretical foundation for the effective use of reproductive hormones in breeding techniques for livestock.

Reproductive factors and breast cancer risk in Palestine: A case control study

BackgroundEarly age at menarche, late age at menopause, and late age at first full-term pregnancy are linked to a modest increase in the risk of developing breast cancer (breast ca). This study aims to investigate the reproductive determinants of breast cancer among women in the West Bank of Palestine.A structured questionnaire was used to collect data in a case-control study (237 registered cases and 237 controls). A multivariate analysis model was used to adjust for the association between women’s reproductive factors and breast ca risk. This study was approved by Al Quds University Ethical Research Committee and the Ministry of Health research unit. ResultsIn the multivariate analysis, menarche after 13 years of age, use of oral contraceptives for more than two months, and hormonal contraceptives use significantly doubled the risk for breast ca (Adjusted Odds Ratio (AOR) = 2.03, 95 % CI: 1.21–4.37, p < 0.011 and AOR = 2.2, 95 % CI: 1.24–4.01, p = 0.008, respectively). Women who used hormone replacement therapy (HRT) were significantly associated with higher odds (5 folds) of having breast ca versus those who did not use them (AOR 5.02, 95 % CI: 1.93–13.06, p = 0.001). Similarly, nulliparous women showed 6 times the odds of breast ca compared with women with one or more children (p = 0.005). Also, parental consanguinity marriage (AOR 2.59, 95 % CI: 1.53–4.36, p = 0.001) and positive family history (AOR 3.88, 95 % CI: 2.19–6.87, p = 0.001) of the condition can be strong determinants for breast ca in this study. ConclusionThis study provides clear evidence that the use of reproductive hormones, whether as a birth control tool or for therapeutic purposes, must be rationalized worldwide and in Palestine in particular.

Reproductive hormone use and its association with herd-level factors on Dutch dairy farms

We studied the use of the 3 commonly used reproductive hormones, namely prostaglandins, GnRH, and progesterone, and associated herd-level factors on 760 Dutch dairy farms from 5 veterinary clinics. From 2017 to 2019 we collected data on the sales of reproductive hormones, converted this data into the number of reproductive hormone doses conducted, and expressed this as the annual number of reproductive hormone doses per 100 adult dairy cows. Additional herd-level information was available for 2019. Due to the excess of zeros in the data set (i.e., a substantial number of farms did not use any hormones), we used a zero-inflated negative binomial model to identify related herd-level factors for the use of reproductive hormones. In the entire study period of 2017 to 2019, 5.8% of the dairy farms did not use any reproductive hormones, with the proportion of nonusers varying between 0.0 and 10.3% per veterinary clinic. This proportion was around 13.5% on an annual basis. Prostaglandins were the most frequently used reproductive hormone in Dutch dairy cows (62.9%), followed by GnRH (33.1%) and progesterone (4.0%). Furthermore, participating in a veterinary herd health management program had a significant effect on reproductive hormone use. These farms used more reproductive hormones than farms that did not participate in a herd health management program and were less represented in the group of nonuser farms. Technologies, such as pedometers and automatic milking systems, also had an effect on reproductive hormone use. The presence of pedometers or activity monitors did not reduce the use of the reproductive hormones but was associated with a greater frequency of users. Farms with an automatic milking system used more reproductive hormones than farms with a conventional milking system. With this study, we have made a first step in achieving transparency in the Dutch dairy industry by providing an objective overview of reproductive hormone use on Dutch dairy farms and identifying associations with some herd-level factors.

Exogenous reproductive hormone use in breast cancer survivors and previvors.

Considerable controversy exists regarding the safety of elective exogenous hormonal exposure among breast cancer survivors and women at high risk of developing the disease (referred to herein as 'previvors'). We performed a qualitative analysis focused on four areas of potential exogenous exposure to hormones among previvors and survivors: hormonal contraception; systemic hormone-replacement therapy (HRT); localized HRT; and hormonal manipulation for fertility preservation or enhancement. Herein, we discuss the available data and present clinical recommendations regarding the safety of hormonal exposure for both previvors and survivors. We found these data to be hampered by small cohort sizes, heterogeneous patient populations, and limited study designs, highlighting a great need to conduct further research with the aim of enabling better-informed patient management.

Survey of reproduction management on Canadian dairy farms.

The objectives of this study were to (1) quantify current reproduction management practices, and (2) assess the association between these practices and herd reproductive performance on dairy farms in Canada. A bilingual survey was developed, validated, and administered from March to May 2014 to collect general and reproduction management and performance measures [annual 21-d pregnancy rate (PR), 21-d insemination rate (IR), and conception risk (CR)]. Associations between management practices and reproductive performance measures were tested using linear regression models. A total of 832 questionnaires were completed online and by mail, representing a response rate of 9%. On average, farms had 77 lactating cows (median=50) and 13 dry cows (median=10), and Holstein was the most common breed (92% of herds). Lactating cow housing was tiestall on 61% of the farms, freestall on 37%, and bedded pack on 2%. The average voluntary waiting period was 58 d in milk (DIM). The main reproduction management practice per farm was defined as the means employed for >50% of inseminations. Farms reported their main reproduction management practice for first and subsequent inseminations, respectively, as visual estrus detection (51 and 44% of herds), timed AI (21 and 23% of herds), automated activity monitoring (AAM; 10 and 10% of herds), other management practice (bulls; 2 and 2% of herds), and a combination of management practices (16 and 21% of herds). On farms using visual estrus detection, cows were observed for signs of estrus on average 3.5 times per day, for an average total of 36 min/d. The most common use of reproductive hormones was to synchronize ovulation using Ovsynch (58% of the farms). Average PR, IR, and CR were 17.6, 44.1, and 40.5%, respectively. In linear regression analyses adjusted for confounders, pregnancy rate was significantly associated with geographic region, housing (tiestall: PR=15.4%, freestall: PR=17.6%), herd size (<50 lactating cows: PR=16.2%, 50-100 cows: PR=16.5%, >100 cows: PR=17.8%), voluntary waiting period (≤60 DIM: PR=17.6%, >60 DIM: PR=15.9%), and frequency of insemination per day (once daily: PR=16.6%, twice or more daily: PR=18.1%). The main reproduction management practice at first and subsequent inseminations was divergently associated with IR and CR, but not with PR (visual heat detection: PR=17.4%, timed AI: PR=18.4%, AAM: PR=17.1%, combined practices: PR=18.2%).

Venous thromboembolism in women: a specific reproductive health risk

BACKGROUND Venous thromboembolism (VTE) is a specific reproductive health risk for women. METHODS Searches were performed in Medline and other databases. The selection criteria were high-quality studies and studies relevant to clinical reproductive medicine. Summaries were presented and discussed by the European Society of Human Reproduction and Embryology Workshop Group. RESULTS VTE is a multifactorial disease with a baseline annual incidence around 50 per 100 000 at 25 years and 120 per 100 000 at age 50. Its major complication is pulmonary embolism, causing death in 1-2% of patients. Higher VTE risk is associated with an inherited thrombophilia in men and women. Changes in the coagulation system and in the risk of clinical VTE in women also occur during pregnancy, with the use of reproductive hormones and as a consequence of ovarian stimulation when hyperstimulation syndrome and conception occur together. In pregnancy, the risk of VTE is increased ~5-fold, while the use of combined hormonal contraception (CHC) doubles the risk and this relative risk is higher with the more recent pills containing desogestrel, gestodene and drospirenone when compared with those with levonorgestrel. Similarly, hormone replacement therapy (HRT) increases the VTE risk 2- to 4-fold. There is a synergistic effect between thrombophilia and the various reproductive risks. Prevention of VTE during pregnancy should be offered to women with specific risk factors. In women who are at high risk, CHC and HRT should be avoided. CONCLUSIONS Clinicians managing pregnancy or treating women for infertility or prescribing CHC and HRT should be aware of the increased risks of VTE and the need to take a careful medical history to identify additional co-existing risks, and should be able to diagnose VTE and know how to approach its prevention.

Sociodemographic, Family History, and Lifestyle Risk Factors for Open-angle Glaucoma and Ocular Hypertension: The Los Angeles Latino Eye Study

To evaluate the relationship between sociodemographic, family history, and lifestyle risk factors and open-angle glaucoma (OAG) and ocular hypertension (OHT) in Latinos. Population-based cohort study. Latinos 40 years and older from 6 census tracts in La Puente, California. Participants underwent an in-home interview and in-clinic examination. Demographic, lifestyle, and family history variables were analyzed as risk factors using multivariable regression models to identify independent associations with OAG or OHT. Open-angle glaucoma and OHT. Two hundred eighty-nine participants were diagnosed as having OAG, 219 were found to have OHT, and 5624 persons had no evidence of either OAG or OHT. After adjustment for intraocular pressure, stepwise logistic regression analyses revealed that older age, male gender, unmarried marital status, and being a first-degree relative were independent risk factors for OAG. For age, the relative risk doubled with each decade. Males and unmarried participants had a higher risk of having glaucoma than females and those who were married (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.30-2.30, and OR, 1.39; 95% CI, 1.03-1.87, respectively). A positive family history of glaucoma in first-degree relatives was a risk factor for OAG (OR, 1.92; 95% CI, 1.25-2.94). Smoking, alcohol use, and female reproductive hormone use were not associated with OAG. Additionally, increasing age, Native American ancestry, unemployed status, and family history of glaucoma were found to be independent factors for increased risk of OHT. Although the mechanisms whereby age and family history lead to increased risk are partly understood, further study is needed to understand the biological significance of the other demographic risk factors identified such as male gender and unmarried status.

Infertility Drugs Do Not Cause Breast Cancer

The widespread use of reproductive hormones has prompted much research on possible associations between these drugs and cancer, but studies have