Fecal microbiota profile of ovariohysterectomized cats submitted to estrogen replacement / Perfil da microbiota fecal de gatas ovariohisterectomizadas submetidas à reposição estrogênica

This study aimed to observe the effects of 17 ß-estradiol replacements on the fecal microbiota in spayed cats. Individual samples of fresh feces were collected and stored at -80° C. Sequencing of the V3/V4 regions of the 16S rRNA gene was used, and bioinformatic analysis was performed. Firmicutes/Bacteriodetes ratio was lower in the group receiving estrogen replacement compared to the SHAM group (P = 0,005). Jaccard index (P = 0.123) and Yue & Clayton index (P = 0.094) did not reveal alpha and beta diversity differences. The linear discriminant analysis effect size (LefSe) identified Firmicutes and MegasPhaera as the biomarkers for the SHAM group, and Burkholderiales, Betaproteobacteria, Sutterellaceae, Suterella, Proteobacteria, Proteobacteria unclassified and Collinsella for the group receiving estrogen replacement.(AU)

O objetivo deste estudo foi observar os efeitos da reposição de 17 ß-estradiol na microbiota fecal de gatas castradas. Amostras individuais de fezes frescas foram colhidas e armazenadas a -80°C. Foi realizado o sequenciamento das regiões V3/V4 do gene 16S rRNA e a análise bioinformática. A razão Firmicutes/Bacteriodetes foi menor no grupo que recebeu reposição estrogênica em comparação ao grupo SHAM (P = 0,005). O índice de Jaccard (P = 0,123) e o índice de Yue & Clayton (P = 0,094) não revelaram diferenças na alfa e beta diversidade. A análise discriminatória linear de tamanho do efeito (LefSe) identificou Firmicutes e Megasphaera como biomarcadores para o grupo SHAM, e Burkholderiales, Betaproteobacteria, Sutterellaceae, Suterella, Proteobacteria, Proteobacteria não classificada e Collinsella para o grupo que recebeu reposição estrogênica.(AU)

Spaying-related urinary incontinence and oestrogen therapy in the bitch.

Some aspects of spaying-related urinary incontinence in the bitch still remain incompletely clarified. Therefore, the aims of the present study were to evaluate the prevalence of the disease among spayed dogs, to detect differences in risk related to the type of surgery, to describe the characteristics of incontinent bitches, to assess the influence of age at surgery on the onset of incontinence occurrence, and to assess the effectiveness and long-term side effects of oestrogen therapy in affected bitches. Among 750 bitches submitted to ovariectomy or ovariohysterectomy, those showing spaying-related urinary incontinence were evaluated. Oestrogen replacement therapy consisted of administering an effective dose followed by an individual maintenance dose. The results showed that the disease occurred in 5% of neutered bitches, the type of surgery did not affect the disease occurrence, affected bitches frequently represented large or giant breeds or large-size mongrels, the body weight of the affected bitches at surgery was often > 20 kg, the disease seems to be associated with tail docking, the age at surgery influences the onset ofincontinence, with earlier occurrence in older bitches, and that a strong co-operation between owners and veterinarians is necessary to achieve successful response to oestrogen replacement therapy. Long-term administration seems to be unrelated to oestrogenic side effects.

Profile of serum IL-1beta and IL-10 shortly after ovariectomy and estradiol replacement in rats.

Ovariectomy leads to progressive and significant increases in body weight gain and osteoporosis and is related to changes in serum and tissue cytokine profiles, such as observed in other models of overweight. We aimed to evaluate serum interleukin-1beta and interleukin-10 shortly after ovariectomy, before the establishment of overweight in rats. Female Wistar rats were submitted to ovariectomy, ovariectomy and estradiol replacement, or sham operation and compared with intact controls. Rats were killed 3, 6, 9, or 13 d after ovariectomy. Body mass and retroperitoneal fats were significant higher only 13 d after ovariectomy, and estradiol replacement to ovariectomized rats impaired both body mass and retroperitoneal fat gain. Shortly after ovariectomy (at 3 d) serum interleukin-1beta levels significantly increased in ovariectomized rats, treated or not with estradiol, while serum interleukin-10 levels increased only 9 d after ovariectomy. Our results suggest the existence of an important interplay between the immune system and ovarian function. This interplay occurs regardless of significant changes in adipose tissue compartment, as ovarian excision leads to short-term changes in the pattern of interleukin-1beta and interleukin-10 cytokine production that precede body weight gain and are not reverted by estradiol replacement.

Long-term ovarian hormone deprivation alters the ability of subsequent oestradiol replacement to regulate choline acetyltransferase protein levels in the hippocampus and prefrontal cortex of middle-aged rats.

The role of oestrogen replacement therapy in preventing or delaying age-associated cognitive decline is controversial. Therapy success may critically depend on the time of treatment initiation following cessation of ovarian function. The present study aimed to assess, in middle-aged rats, whether the ability of oestradiol to modulate the cholinergic system depends on the timing of treatment initiation following ovariectomy. Using western blotting, protein levels of choline acetyltransferase (ChAT) were measured in the hippocampus and prefrontal cortex (PFC), which are both important areas with respect to cognitive function. In an initial experiment, we established the effects of oestradiol delivered via implanted capsules on ChAT levels in the hippocampus and PFC of young adult animals. In a second experiment, we tested the ability of the same oestradiol treatment paradigm to affect ChAT protein in 15-month-old middle-aged rats that had been ovariectomised either at the age of 10 months or at 15 months. In both experiments, rats were sacrificed 10 days after receiving implants and ChAT protein levels were measured. In both young adult and middle-aged animals, oestradiol treatment initiated immediately after ovariectomy significantly increased ChAT levels in the hippocampus but not in the PFC compared to cholesterol control treatment. However, when oestradiol treatment was initiated 5 months after ovariectomy, it failed to significantly increase ChAT levels in the hippocampus, but did so in the PFC. These data indicate that, after prolonged ovarian hormone deprivation, the ability of subsequent oestradiol treatment to modulate ChAT protein levels is altered in a site-specific manner.

Hormone therapy effects on social behavior and activity levels of surgically postmenopausal cynomolgus monkeys.

The purpose of the experiments reported here was to investigate central nervous system effects of commonly prescribed postmenopausal hormone therapies in a primate model, the cynomolgus monkey (Macaca fascicularis). The results of two experiments are reported. In the first, ovariectomized adult cynomolgus monkeys were treated for eight weeks each with oral micronized 17beta-estradiol (E2) (n=23), E2+medroxyprogesterone acetate (MPA) (n=23), E2+progesterone (P4) (n=23), and placebo (n=23) using a crossover design. In the second, ovariectomized adult cynomolgus monkeys were treated for eight weeks with oral micronized E2+oral micronized P4 (n=10), or E2+intravaginal micronized P4 delivered via a Silastic ring (n=8), or oral placebo and intravaginal placebo (n=5), using a parallel arm design. Behavior was recorded during weeks two through four. Cerebrospinal fluid (CSF) and blood were sampled, and 24h heart rate recorded by telemetry during weeks five through seven. Monoaminergic metabolites were assayed in CSF, and cortisol was assayed in serum. There were no significant effects of treatment on CSF monoaminergic metabolites or heart rate. E2+MPA increased cortisol concentrations. While there were some differences in effects between experiments, both progestogens and both routes of administration increased time spent resting, particularly resting in body contact, resulting in increased passive affiliative interaction. Thus, synthetic progestogens appear to be as sedating as progesterone, and the ring delivery system does not appear to protect the central nervous system from effects of progestogens. Further research is needed to explore social context as an important feature of behavioral response to steroid hormone regimens and to verify and extend knowledge of systemic effects of vaginal ring-delivered progestogens.

Densidade mineral óssea em cadelas submetidas à ovarioisterectomia com e sem reposição estrogênica oral / Mineral density in bones of ovariohysterectomized bitches, with or without oral estrogen replacement / Mineral density in bones of ovariohysterectomized bitches, with or without oral estrogen replacement

Estudaram-se os efeitos da ovarioisterectomia na densidade mineral óssea de cadelas e da reposição de estrógenos após a cirurgia. Foram utilizadas 12 cadelas, sem raça definida, entre dois e seis anos de idade e pesos entre 5 e 15kg. Os animais, submetidos à ovarioisterectomia, foram separados em dois grupos de seis. Um grupo serviu como controle, e o outro recebeu estrógenos naturais conjugados na dose de 0,01mg/kg via oral a cada 48 horas, durante 12 meses. No dia da cirurgia e após 12 meses, foram feitas radiografias com vistas à densitometria óptica em imagem radiográfica. A ovarioisterectomia diminuiu a densidade óssea, e a reposição estrogênica, na dose utilizada, foi capaz de preservá-la.

Effects on bone density of ovariohysterectomy and post-operative estrogen replacement were studied in bitches. Twelve mixed-breed bitches, ranging from 2 to 6 years of age and weighing between 5 and 15kg were submitted to ovariohysterectomy and separated in two groups of six, after a period of adaptation of 60 days. Bitches from the first group were an un-innoculated control; whereas treated bitches received 0.01mg/kg per os of natural estrogen every 48 hours for 12 months. Radiographs were taken on the day of surgery and 12 months later. Variation in bone density was quantified by optic densitometry in radiographic images. Ovariohysterectomy decreased bone density, whereas estrogen replacement moderated the effect.

Estrogen replacement therapy induces telomerase RNA expression in the macaque endometrium.

OBJECTIVE: To evaluate the effects of hormonal therapies on the expression of telomerase RNA (TRNA) in the endometrium of ovariectomized female cynomolgus macaques (Macaca fascicularis). DESIGN: Randomized long-term experimental trial. SETTING: Animal study at an academic research institution. PATIENT(S): Surgically postmenopausal cynomolgus macaques. INTERVENTION(S): Treatments were given in the diet for three years and included conjugated equine estrogens (CEE), CEE + medroxyprogesterone acetate (MPA), and tamoxifen, at clinically relevant doses. MAIN OUTCOME MEASURE(S): Expression of TRNA within the basal glands, basal stroma, superficial glands, and superficial stroma of the endometrium by radiolabeled in situ hybridization. RESULT(S): Conjugated equine estrogens increased glandular TRNA expression, and the addition of MPA decreased this effect. Tamoxifen induced glandular TRNA expression to a lesser degree. Both CEE + MPA and tamoxifen increased stromal TRNA expression. The expression of TRNA in the endometrial glands was always greater than TRNA expression in the stroma. Treatment groups with greater proliferation and progesterone receptor expression also had elevated TRNA; within-group correlations were not significant. No statistically significant difference occurred between the basal and superficial endometrial layers. CONCLUSION(S): These results show for the first time a cell-specific hormonal regulation of TRNA in the primate endometrium, with up-regulation of TRNA by treatments associated with increased risk of endometrial cancer in women.

Associations between age, parity, hormonal therapy and breed, and pyometra in Finnish dogs.

A case-control study of 953 dogs with pyometra and 10,660 unmatched control dogs was used to investigate the relationships between age, parity, hormonal therapy and breed, and pyometra in Finnish dogs. Cases were reported in animals between nine months and 18 years of age, with a median age at diagnosis of nine years. Nulliparous bitches had a moderately higher risk of developing pyometra than primiparous and multiparous animals (adjusted odds ratio point estimate, 6.63). The administration of oestrogen increased the risk of pyometra in bitches up to four years of age (odds ratio point estimate > 6). No significant risk-enhancing effect of progestin treatment was detected and it is unlikely that such a risk, if present, is high (likelihood of the odds ratio exceeding 2 < 0.18). Seventeen breeds had an increased risk, and the wire-haired dachshund and mongrels had a decreased risk of developing the condition.