Nicolas Noyola
Member
- Joined
- Apr 5, 2018
- Messages
- 88
if anybody is interested in talking about aromatase inhibitors, i have a bunch of studies ive been meaning to dump. many show positive effects of AIs, some show negative effects also. I don't really know the mechanism behind why the aromatase enzyme is inhibited, and why the overinhibition of the enzyme would be counterproductive to health.
[A study on testicular aromatase activity--spermatogenic damage in high testicular E2 models of rat]. - PubMed - NCBI
A study on testicular aromatase activity
Exp. 1: In the hCG group, the rate of testicular aromatase activity and testicular E2 level were higher and the diameter of seminiferous tubules was smaller than in the control group. However, these changes were not observed in the hCG+A.I. group. Exp. 2: In the Emcs group, testicular E2 level showed an increase without elevation of serum E2 level, and the diameter of seminiferous tubules was atrophic.
Acute inhibition of neurosteroid estrogen synthesis suppresses status epilepticus in an animal model. - PubMed - NCBI
Acute inhibition of neurosteroid estrogen synthesis suppresses status epilepticus in an animal model.
Hippocampal E2 levels were higher in rats experiencing more severe seizures. Consistent with a seizure-promoting effect of hippocampal estrogen synthesis, intra-hippocampal aromatase inhibition also suppressed seizures. These results reveal neurosteroid estrogen synthesis as a previously unknown factor in the escalation of seizures and suggest that acute administration of aromatase inhibitors may be an effective treatment for SE.
Aromatase inhibition abolishes LTP generation in female but not in male mice. - PubMed - NCBI
Aromatase inhibition abolishes LTP generation in female but not in male mice. (According to the study: LTP is an electrophysiological marker of memory.)
(this seems to occur frequently, that inhibition of aromatase exerts far greater negative effects in females than males)
Aromatase inhibition by letrozole attenuates kainic acid-induced seizures but not neurotoxicity in mice. - PubMed - NCBI
Aromatase inhibition by letrozole attenuates kainic acid-induced seizures but not neurotoxicity in mice:
"Reduction of testosterone by aromatase generates proconvulsant 17-β estradiol. Alternatively, testosterone is metabolized into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR) to form anticonvulsant metabolite 3α-androstanediol (3α-Diol), a potent GABAA receptor modulating neurosteroid. The present study evaluated whether inhibition of aromatase inhibitor letrozole protects against seizures and neuronal degeneration induced by kainic acid (KA) (10 mg/kg, i.p.) in Swiss albino mice. Letrozole (1 mg/kg, i.p.) administered one hour prior to KA significantly increased the onset time of seizures and reduced the% incidence of seizures. Pretreatment with finasteride, a selective inhibitor of 5α-reductase and indomethacin, a selective inhibitor of 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR), reversed the protective effects of letrozole in KA-induced seizures in mice. Microscopic examination using cresyl violet staining revealed that letrozole did not modify KA-induced neurotoxicity in the CA1, CA3 and DG region of the hippocampus. Letrozole treatment resulted in the reduced levels of 17-β estradiol and elevated the levels of 5α-dihydrotestosterone (DHT) and 3α-Diol in the hippocampus. Finasteride and indomethacin attenuated letrozole-induced elevations of 5α-DHT and 3α-Diol. Our results indicate the potential anticonvulsant effects of letrozole against KA-induced seizures in mice that might be mediated by inhibiting aromatization of testosterone to 17β-estradiol, a proconvulsant hormone and by redirecting the synthesis to anticonvulsant metabolites, 5α-DHT and 3α-Diol. Acute aromatase inhibition, thus, might be used as an adjuvant in the treatment of status epilepticus and can be pursued further.
Aromatase inhibition in the dog. I. Effect on serum LH, serum testosterone concentrations, testicular secretions and spermatogenesis. - PubMed - NCBI
Aromatase inhibition in dogs
tldr; low estrogen and estrogen metabolites and much higher T, androstenedione, and DHT in dogs given an AI, but no effect on spermatogenesis
Aromatase inhibitor letrozole downregulates steroid receptor coactivator-1 in specific brain regions that primarily related to memory, neuroendocri... - PubMed - NCBI
Aromatase inhibitor letrozole downregulates steroid receptor coactivator-1 in specific brain regions that primarily related to memory, neuroendocrine and integration.
"In the hippocampus, levels of estradiol content, androgen receptor, estrogen receptor α and β also decreased significantly after letrozole injection. The above results demonstrated letrozole downregulation of SRC-1 in specific regions that are primarily related to learning and memory, cognition and mood, neuroendocrine as well as information integration, indicating that SRC-1 may be one important downstream central target of letrozole. Furthermore, these potential central adverse effects of letrozole should be taken into serious considerations."
Effects of aromatase inhibition in hypogonadal older men: a randomized, double-blind, placebo-controlled trial. - PubMed - NCBI
Effects of aromatase inhibition in hypogonadal older men: a randomized, double-blind, placebo-controlled trial:
Testosterone levels increased from 11.2 +/- 3.3 nmol/L at baseline to 18.2 +/- 4.8 nmol/L at month 3
(p < 0.0001 vs. placebo) while bioavailable testosterone levels increased from 2.7 +/- 0.8 nmol/L at baseline to 5.4 +/- 1.7 nmol/L at month 3 (p < 0.0001 vs. placebo). Testosterone and biotestosterone levels peaked at month 3 and then declined by month 12 (though they remained significantly higher than baseline and greater than placebo). Estradiol levels decreased from 55.8 +/- 15.4 pmol/L at baseline to 42.2 +/- 13.6 pmol/L at month 3 and then remained stable (p < 0.0001). Body composition and strength did not change, nor did PSA, BPH symptoms, hematocrit or lipid levels.
Effects of Aromatase Inhibition on the Physical Activity Levels of Male Mice
Effects of Aromatase Inhibition on the Physical Activity Levels of Male Mice
"Orchidectomy significantly reduced wheel running activity. Steroid replacement recovered wheel running to pre-surgical levels; however, aromatase inhibition did not further affect wheel running levels. The recovery of wheel running in mice with androgen supplementation and the further persistence of wheel running in mice with compromised aromatase function suggests that the androgens—testosterone in particular—may directly affect wheel running patterns in male mice.
....................................stuff that ive omitted for brevity.............................
Currently, it is suggested that testosterone requires conversion to an estrogenic compound before any modulatory interactions to the wheel running response will occur. Roy and Wade [14] administered aromatizable and non-aromatizable forms of androgens to orchidectomized rats. The aromatizable androgen notably increased wheel running, but administration of the non-aromatizable molecule resulted in continued quiescence.
Supporting Roy and Wade’s earlier study, Watai et al. [15] found that wheel running activity was hindered in an estrogen-deficient aromatase knockout mouse model. Conversely, Hill et al. [16], using a similar aromatase knockout model found that the male knockout animals ran nearly twice as far as wild type animals, an observation that was reversed in three weeks with the administration of 17β-estradiol. While the use of knockout animals can lead to difficulties with interpretation due to issues arising during development [17], it is interesting that the two studies using aromatase knockout animals resulted in completely opposite results."
Effects of letrozole on hippocampal and cortical catecholaminergic neurotransmitter levels, neural cell adhesion molecule expression and spatial le... - PubMed - NCBI
Effects of letrozole on hippocampal and cortical catecholaminergic neurotransmitter levels, neural cell adhesion molecule expression and spatial learning and memory in female rats.
this one has a really long abstract so im going to summarize it: tldr; letrozole in female rats(no male rats in this study) decreases dopamine, noradrenaline, and their metabolites in the hippocamus, but improves spatial memory nonetheless.
Impact of aromatase inhibitor therapy on bone turnover, cortical bone growth and vertebral morphology in pre- and peripubertal boys with idiopathic... - PubMed - NCBI
Impact of aromatase inhibitor therapy on bone turnover, cortical bone growth and vertebral morphology in pre- and peripubertal boys with idiopathic short stature.
In letrozole-treated boys, the concentrations of the bone resorption marker urine aminoterminal telopeptide of type I collagen initially increased and thereafter slowly declined while the concentrations of the bone formation markers serum aminoterminal propeptide of type I collagen and serum alkaline phosphatase remained unchanged or slightly increased, respectively. In placebo-treated boys, all markers of bone turnover increased significantly during treatment. Among those who progressed into puberty, metacarpal index (MCI) increased more in the letrozole-treated than in the placebo-treated boys during treatment (25 vs. 9%, p = 0.007). The change in MCI correlated with the testosterone-to-estradiol ratio (r = 0.59, p = 0.02). Vertebral deformities were detected in 6 out of 13 boys receiving letrozole and in 4 out of 11 receiving placebo (p = 0.70). Aromatase inhibition suppresses bone turnover, possibly through an androgen-mediated effect. In pubertal boys, treatment stimulates cortical bone growth by increasing the testosterone-to-estradiol ratio.
Effect of chronic administration of an aromatase inhibitor to adult male rats on pituitary and testicular function and fertility. - PubMed - NCBI
Effect of chronic administration of an aromatase inhibitor to adult male rats on pituitary and testicular function and fertility.
The aim of the present study was to evaluate the effects of the administration of a potent non-steroidal aromatase inhibitor, anastrozole, on male reproductive function in adult rats. As anastrozole was to be administered via the drinking water, a preliminary study was undertaken in female rats and showed that this route of administration was effective in causing a major decrease in uterine weight (P<0.02). In an initial study in male adult rats, anastrozole (100 mg/l or 400 mg/l) was administered via the drinking water for a period of 9 weeks. Treatment with either dose resulted in a significant increase ( approximately 10%) in testis weight and increase in plasma FSH concentrations (P<0.01) throughout the 9 weeks. Mating was altered in both groups of anastrozole-treated rats, as they failed to produce copulatory plugs. Histological evaluation of the testes from anastrozole-treated rats revealed that spermatogenesis was grossly normal. In a more detailed study, adult rats were treated with 200 mg/l anastrozole via the drinking water for periods ranging from 2 weeks to 1 year. Plasma FSH and testosterone concentrations were increased significantly (P<0.001) during the first 19 weeks of treatment. However, LH concentrations were increased only at 19 weeks (P<0.001) in anastrozole-treated rats, and this coincided with a further increase in circulating and intratesticular testosterone concentrations (P<0.05). No consistent change in inhibin-B concentrations was observed during the study. Suppression of plasma oestradiol concentrations could not be demonstrated in anastrozole-treated animals, but oestradiol concentrations in testicular interstitial fluid were reduced by 18% (P<0.01). Mating was again inhibited by anastrozole treatment, but could be restored by s.c. injection of oestrogen, enabling demonstration that rats treated for 10 weeks or 9 months were still fertile. Testis weight was increased by 19% and 6% after treatment for 19 weeks and 1 year, respectively. Body weight was significantly decreased (P<0.01) by 19 weeks of anastrozole treatment; after 1 year the animals appeared to have less fat as indicated by a 27% decrease in the weight of the gonadal fat pad . The majority of anastrozole-treated animals had testes with normal spermatogenesis but, occasionally, seminiferous tubules showed abnormal loss of germ cells or contained only Sertoli cells. Ten percent of anastrozole-treated animals had testes that appeared to contain only Sertoli cells, and one rat had 'giant' testes in which the tubule lumens were severely dilated. Morphometric analysis of the normal testes at 19 weeks showed no difference in the number of Sertoli cells or germ cells, or the percentage volumes of the seminiferous epithelium, tubule lumens and interstitium between control and anastrozole-treated rats. On the basis of the present findings, oestrogen appears to be involved in the regulation of FSH secretion and testosterone production, and is also essential for normal mating behaviour in male rats. Furthermore, these data suggest that the brain and the hypothalamo-pituitary axis are considerably more susceptible than is the testis to the effects of an aromatase inhibitor. Anastrozole treatment has resulted in a model of brain oestrogen insufficiency.
if i understand this study correctly the AI increased testis weight by 35%...
https://www.researchgate.net/publication/306368393_Treatment_of_Young_Rats_with_the_Aromatase_Inhibitor_Exemestane_Reduces_Testicular_Weight_and_Sertoli_Cell_Numbers
There were no effects on sexual maturation in either sex or on female
reproductive function. Treatment of juvenile male rats caused increased cohabitation time and decreased copulation
rates; pregnancy rates and litter size were not affected in rats that mated. Decreased testis (10–15%) and epididymis (20–
30%) weights, and decreased Sertoli cell numbers were noted at all doses. This indicates that exemestane can reduce
Sertoli cell proliferation during maturation. The sensitive window for this effect is expected to be limited to the period of
Sertoli cell proliferation, which is completed by around postnatal day 15 in rats and before puberty in humans. Treatment
beginning at a later time relative to the window for Sertoli cell proliferation or for a longer duration is not expected to
have additional adverse effect as the effect was not shown to be degenerative. Birth Defects Res (Part B) 92:304–313,
2011.
Changes induced by treatment with aromatase inhibitors in testicular Leydig cells of rats and dogs. - PubMed - NCBI
Changes induced by treatment with aromatase inhibitors in testicular Leydig cells of rats and dogs.
Treatment of male rats and dogs with CGP 32,349 (formestane), a steroidal aromatase inhibitor, and CGS 20,267 (letrozole), a non-steroidal aromatase inhibitor, induced different alterations in testicular interstitial Leydig cells in the two species. Whereas in dogs Leydig cells were hypertrophic and hyperplastic, in rats either no effect (CGS 20,267) or atrophy of Leydig cells (CGP 32,349) was reported. The different response of the two species can be explained by different regulating mechanisms of gonadotropin secretion by the anterior pituitary.
Testis morphology in rats chronically treated with letrozole, an aromatase inhibitor. - PubMed - NCBI
Testis morphology in rats chronically treated with letrozole, an aromatase inhibitor.
The aim of this study was to investigate the influence of the long-term treatment of rats with letrozole on the testis morphology. The pharmacologically induced estrogen deficiency caused statistically significant decreases of both intratesticular and serum levels of estradiol, and morphological changes in the seminiferous epithelium and in the interstitial tissue of the testes. Six months of treatment resulted in the sloughing of premature germ cells of the seminiferous epithelium into the tubular lumen and in intraepithelial vacuolization. Multinucleated giant cells composed of premature germ cells, conglomerates of various cell nuclei and cell debris as well as irregularities and infoldings of the tubular basement membrane were also seen. Moreover, deep invaginations of the lamina propria with myoid cells were observed. Cells in the interstitial tissue showed changes similar to that observed in aging processes. The cytoplasm of LH-R-positive Leydig cells was loaded with lipofuscin granule( so aged testis essentially ? ?). The number of lipofuscin-loaded cells was significantly increased in the interstitial tissue of testis in letrozole-treated rats. The results indicate the direct influence of estrogens on seminiferous tubules and the interstitial tissue morphology.
https://onlinelibrary.wiley.com/doi/pdf/10.2164/jandrol.05195
Reducing Estrogen Synthesis in Developing Boars Increases Testis Size and Total Sperm Production
"Testes of aromatase-inhibited boars initially exhibited delayed lumen formation, lower testicular weight, fewer detergentresistant spermatids, and fewer Sertoli cells, but by 7 to 8 months, these boars had recovered and had larger testes, more detergentresistant spermatids per testis, and more Sertoli cells. Total Leydig cell volume increased in proportion to testis size. Reducing endogenous estrogen is consistent with a delay in testicular maturation/puberty that allows for a longer window for the proliferation of Sertoli cells and maturation of Leydig cells, resulting in larger testes and higher spermatid production."
P450-aromatase activity and expression in human testicular tissues with severe spermatogenic failure. - PubMed - NCBI
P450-aromatase activity and expression in human testicular tissues with severe spermatogenic failure.
There is evidence that impaired spermatogenesis is associated with an imbalance in the oestradiol/testosterone ratio and with Leydig cell (LC) dysfunction. In testis, P450-aromatase, encoded by CYP19, is responsible for the conversion of testosterone to oestradiol. The aims of this study were to quantify CYP19 mRNA expression, aromatase activity and protein localization, and to measure the oestradiol to testosterone ratio in testicular tissues of men with spermatogenic impairment. Twenty-four men with complete Sertoli cell-only syndrome (SCOS), 14 with focal SCOS, 14 with maturation arrest (MA), 8 with mixed atrophy and 30 controls with normal spermatogenesis were subjected to testicular biopsy. All subjects underwent a physical examination, cytogenetic and serum hormonal studies. Testicular CYP19 mRNA was quantified using real time RT-PCR. Testicular aromatase activity was measured using the (3)H(2)0 assay and protein expression was evaluated using immunohistochemistry. In cases, serum testosterone and oestradiol were normal, but the testosterone/LH ratio was lower compared with controls (p < 0.05). Aromatase was localized in the Leydig, Sertoli and germ cells of all tissues, although stronger intensity was observed in LC. Aromatase mRNA and activity were not altered in cases and correlated positively with LC number (r = 0.516 and r = 0.369; p < 0.008). The intratesticular oestradiol/testosterone ratio was elevated (p = 0.005) in complete SCOS patients compared with controls. In conclusion, testicular aromatase seems to be normal in most subjects with impaired spermatogenesis. However, an altered intratesticular oestradiol/testosterone ratio in some patients with complete SCOS suggests that aromatase is increased, which might contribute to Leydig cell dysfunction.
https://academic.oup.com/biolreprod/article/81/Suppl_1/19/2955088
Sertoli Cell Numbers Increase Rapidly After Aromatase Inhibition in Young Boars.
tldr; AI-treated young boars have bigger testis and more sertoli cells
https://www.researchgate.net/publication/7599892_Reducing_Estrogen_Synthesis_Does_Not_Affect_Gonadotropin_Secretion_in_the_Developing_Boar
tldr; Treatment with the aromatase inhibitor reduced testicular aromatase activity by 90% and decreased E2 and ECs without changing acute, long-term, or postcastration LH and FSH. Plasma T, testicular T, and circulating INH concentrations did not change. Testicular INH was elevated in treated boars compared with controls. In conclusion, estrogen does not appear to play a regulatory role on gonadotropin secretion in the developing boar. This is in direct contrast to findings in males of several other species (maybe this explains different results on different animals w/ AI treatment thinking_emoji)
https://www.sciencedirect.com/science/article/pii/S0016648016300442
Effect of Letrozole, a selective aromatase inhibitor, on testicular activities in adult mice: Both in vivo and in vitro study
Letrozole suppresses spermatogenesis by reducing insulin sensitivity and glucosetransport in the testis. Decreased insulin sensitivity inhibits the glucose transport in the testis by suppressing GLUT8.
ill limit the studies to these ones for now. i wish i had more negative studies but this is what i have so far.
in actual human trials, the effects of AIs seem mostly positive in males. females idk so much.
~comments welcome~
[A study on testicular aromatase activity--spermatogenic damage in high testicular E2 models of rat]. - PubMed - NCBI
A study on testicular aromatase activity
Exp. 1: In the hCG group, the rate of testicular aromatase activity and testicular E2 level were higher and the diameter of seminiferous tubules was smaller than in the control group. However, these changes were not observed in the hCG+A.I. group. Exp. 2: In the Emcs group, testicular E2 level showed an increase without elevation of serum E2 level, and the diameter of seminiferous tubules was atrophic.
Acute inhibition of neurosteroid estrogen synthesis suppresses status epilepticus in an animal model. - PubMed - NCBI
Acute inhibition of neurosteroid estrogen synthesis suppresses status epilepticus in an animal model.
Hippocampal E2 levels were higher in rats experiencing more severe seizures. Consistent with a seizure-promoting effect of hippocampal estrogen synthesis, intra-hippocampal aromatase inhibition also suppressed seizures. These results reveal neurosteroid estrogen synthesis as a previously unknown factor in the escalation of seizures and suggest that acute administration of aromatase inhibitors may be an effective treatment for SE.
Aromatase inhibition abolishes LTP generation in female but not in male mice. - PubMed - NCBI
Aromatase inhibition abolishes LTP generation in female but not in male mice. (According to the study: LTP is an electrophysiological marker of memory.)
(this seems to occur frequently, that inhibition of aromatase exerts far greater negative effects in females than males)
Aromatase inhibition by letrozole attenuates kainic acid-induced seizures but not neurotoxicity in mice. - PubMed - NCBI
Aromatase inhibition by letrozole attenuates kainic acid-induced seizures but not neurotoxicity in mice:
"Reduction of testosterone by aromatase generates proconvulsant 17-β estradiol. Alternatively, testosterone is metabolized into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR) to form anticonvulsant metabolite 3α-androstanediol (3α-Diol), a potent GABAA receptor modulating neurosteroid. The present study evaluated whether inhibition of aromatase inhibitor letrozole protects against seizures and neuronal degeneration induced by kainic acid (KA) (10 mg/kg, i.p.) in Swiss albino mice. Letrozole (1 mg/kg, i.p.) administered one hour prior to KA significantly increased the onset time of seizures and reduced the% incidence of seizures. Pretreatment with finasteride, a selective inhibitor of 5α-reductase and indomethacin, a selective inhibitor of 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR), reversed the protective effects of letrozole in KA-induced seizures in mice. Microscopic examination using cresyl violet staining revealed that letrozole did not modify KA-induced neurotoxicity in the CA1, CA3 and DG region of the hippocampus. Letrozole treatment resulted in the reduced levels of 17-β estradiol and elevated the levels of 5α-dihydrotestosterone (DHT) and 3α-Diol in the hippocampus. Finasteride and indomethacin attenuated letrozole-induced elevations of 5α-DHT and 3α-Diol. Our results indicate the potential anticonvulsant effects of letrozole against KA-induced seizures in mice that might be mediated by inhibiting aromatization of testosterone to 17β-estradiol, a proconvulsant hormone and by redirecting the synthesis to anticonvulsant metabolites, 5α-DHT and 3α-Diol. Acute aromatase inhibition, thus, might be used as an adjuvant in the treatment of status epilepticus and can be pursued further.
Aromatase inhibition in the dog. I. Effect on serum LH, serum testosterone concentrations, testicular secretions and spermatogenesis. - PubMed - NCBI
Aromatase inhibition in dogs
tldr; low estrogen and estrogen metabolites and much higher T, androstenedione, and DHT in dogs given an AI, but no effect on spermatogenesis
Aromatase inhibitor letrozole downregulates steroid receptor coactivator-1 in specific brain regions that primarily related to memory, neuroendocri... - PubMed - NCBI
Aromatase inhibitor letrozole downregulates steroid receptor coactivator-1 in specific brain regions that primarily related to memory, neuroendocrine and integration.
"In the hippocampus, levels of estradiol content, androgen receptor, estrogen receptor α and β also decreased significantly after letrozole injection. The above results demonstrated letrozole downregulation of SRC-1 in specific regions that are primarily related to learning and memory, cognition and mood, neuroendocrine as well as information integration, indicating that SRC-1 may be one important downstream central target of letrozole. Furthermore, these potential central adverse effects of letrozole should be taken into serious considerations."
Effects of aromatase inhibition in hypogonadal older men: a randomized, double-blind, placebo-controlled trial. - PubMed - NCBI
Effects of aromatase inhibition in hypogonadal older men: a randomized, double-blind, placebo-controlled trial:
Testosterone levels increased from 11.2 +/- 3.3 nmol/L at baseline to 18.2 +/- 4.8 nmol/L at month 3
(p < 0.0001 vs. placebo) while bioavailable testosterone levels increased from 2.7 +/- 0.8 nmol/L at baseline to 5.4 +/- 1.7 nmol/L at month 3 (p < 0.0001 vs. placebo). Testosterone and biotestosterone levels peaked at month 3 and then declined by month 12 (though they remained significantly higher than baseline and greater than placebo). Estradiol levels decreased from 55.8 +/- 15.4 pmol/L at baseline to 42.2 +/- 13.6 pmol/L at month 3 and then remained stable (p < 0.0001). Body composition and strength did not change, nor did PSA, BPH symptoms, hematocrit or lipid levels.Effects of Aromatase Inhibition on the Physical Activity Levels of Male Mice
Effects of Aromatase Inhibition on the Physical Activity Levels of Male Mice
"Orchidectomy significantly reduced wheel running activity. Steroid replacement recovered wheel running to pre-surgical levels; however, aromatase inhibition did not further affect wheel running levels. The recovery of wheel running in mice with androgen supplementation and the further persistence of wheel running in mice with compromised aromatase function suggests that the androgens—testosterone in particular—may directly affect wheel running patterns in male mice.
....................................stuff that ive omitted for brevity.............................
Currently, it is suggested that testosterone requires conversion to an estrogenic compound before any modulatory interactions to the wheel running response will occur. Roy and Wade [14] administered aromatizable and non-aromatizable forms of androgens to orchidectomized rats. The aromatizable androgen notably increased wheel running, but administration of the non-aromatizable molecule resulted in continued quiescence.
Supporting Roy and Wade’s earlier study, Watai et al. [15] found that wheel running activity was hindered in an estrogen-deficient aromatase knockout mouse model. Conversely, Hill et al. [16], using a similar aromatase knockout model found that the male knockout animals ran nearly twice as far as wild type animals, an observation that was reversed in three weeks with the administration of 17β-estradiol. While the use of knockout animals can lead to difficulties with interpretation due to issues arising during development [17], it is interesting that the two studies using aromatase knockout animals resulted in completely opposite results."
Effects of letrozole on hippocampal and cortical catecholaminergic neurotransmitter levels, neural cell adhesion molecule expression and spatial le... - PubMed - NCBI
Effects of letrozole on hippocampal and cortical catecholaminergic neurotransmitter levels, neural cell adhesion molecule expression and spatial learning and memory in female rats.
this one has a really long abstract so im going to summarize it: tldr; letrozole in female rats(no male rats in this study) decreases dopamine, noradrenaline, and their metabolites in the hippocamus, but improves spatial memory nonetheless.
Impact of aromatase inhibitor therapy on bone turnover, cortical bone growth and vertebral morphology in pre- and peripubertal boys with idiopathic... - PubMed - NCBI
Impact of aromatase inhibitor therapy on bone turnover, cortical bone growth and vertebral morphology in pre- and peripubertal boys with idiopathic short stature.
In letrozole-treated boys, the concentrations of the bone resorption marker urine aminoterminal telopeptide of type I collagen initially increased and thereafter slowly declined while the concentrations of the bone formation markers serum aminoterminal propeptide of type I collagen and serum alkaline phosphatase remained unchanged or slightly increased, respectively. In placebo-treated boys, all markers of bone turnover increased significantly during treatment. Among those who progressed into puberty, metacarpal index (MCI) increased more in the letrozole-treated than in the placebo-treated boys during treatment (25 vs. 9%, p = 0.007). The change in MCI correlated with the testosterone-to-estradiol ratio (r = 0.59, p = 0.02). Vertebral deformities were detected in 6 out of 13 boys receiving letrozole and in 4 out of 11 receiving placebo (p = 0.70). Aromatase inhibition suppresses bone turnover, possibly through an androgen-mediated effect. In pubertal boys, treatment stimulates cortical bone growth by increasing the testosterone-to-estradiol ratio.
Effect of chronic administration of an aromatase inhibitor to adult male rats on pituitary and testicular function and fertility. - PubMed - NCBI
Effect of chronic administration of an aromatase inhibitor to adult male rats on pituitary and testicular function and fertility.
The aim of the present study was to evaluate the effects of the administration of a potent non-steroidal aromatase inhibitor, anastrozole, on male reproductive function in adult rats. As anastrozole was to be administered via the drinking water, a preliminary study was undertaken in female rats and showed that this route of administration was effective in causing a major decrease in uterine weight (P<0.02). In an initial study in male adult rats, anastrozole (100 mg/l or 400 mg/l) was administered via the drinking water for a period of 9 weeks. Treatment with either dose resulted in a significant increase ( approximately 10%) in testis weight and increase in plasma FSH concentrations (P<0.01) throughout the 9 weeks. Mating was altered in both groups of anastrozole-treated rats, as they failed to produce copulatory plugs. Histological evaluation of the testes from anastrozole-treated rats revealed that spermatogenesis was grossly normal. In a more detailed study, adult rats were treated with 200 mg/l anastrozole via the drinking water for periods ranging from 2 weeks to 1 year. Plasma FSH and testosterone concentrations were increased significantly (P<0.001) during the first 19 weeks of treatment. However, LH concentrations were increased only at 19 weeks (P<0.001) in anastrozole-treated rats, and this coincided with a further increase in circulating and intratesticular testosterone concentrations (P<0.05). No consistent change in inhibin-B concentrations was observed during the study. Suppression of plasma oestradiol concentrations could not be demonstrated in anastrozole-treated animals, but oestradiol concentrations in testicular interstitial fluid were reduced by 18% (P<0.01). Mating was again inhibited by anastrozole treatment, but could be restored by s.c. injection of oestrogen, enabling demonstration that rats treated for 10 weeks or 9 months were still fertile. Testis weight was increased by 19% and 6%
after treatment for 19 weeks and 1 year, respectively. Body weight was significantly decreased (P<0.01) by 19 weeks of anastrozole treatment; after 1 year the animals appeared to have less fat as indicated by a 27% decrease in the weight of the gonadal fat pad . The majority of anastrozole-treated animals had testes with normal spermatogenesis but, occasionally, seminiferous tubules showed abnormal loss of germ cells or contained only Sertoli cells. Ten percent of anastrozole-treated animals had testes that appeared to contain only Sertoli cells, and one rat had 'giant' testes in which the tubule lumens were severely dilated. Morphometric analysis of the normal testes at 19 weeks showed no difference in the number of Sertoli cells or germ cells, or the percentage volumes of the seminiferous epithelium, tubule lumens and interstitium between control and anastrozole-treated rats. On the basis of the present findings, oestrogen appears to be involved in the regulation of FSH secretion and testosterone production, and is also essential for normal mating behaviour in male rats. Furthermore, these data suggest that the brain and the hypothalamo-pituitary axis are considerably more susceptible than is the testis to the effects of an aromatase inhibitor. Anastrozole treatment has resulted in a model of brain oestrogen insufficiency.if i understand this study correctly the AI increased testis weight by 35%...
https://www.researchgate.net/publication/306368393_Treatment_of_Young_Rats_with_the_Aromatase_Inhibitor_Exemestane_Reduces_Testicular_Weight_and_Sertoli_Cell_Numbers
There were no effects on sexual maturation in either sex or on female
reproductive function. Treatment of juvenile male rats caused increased cohabitation time and decreased copulation
rates; pregnancy rates and litter size were not affected in rats that mated. Decreased testis (10–15%) and epididymis (20–
30%) weights, and decreased Sertoli cell numbers were noted at all doses. This indicates that exemestane can reduce
Sertoli cell proliferation during maturation. The sensitive window for this effect is expected to be limited to the period of
Sertoli cell proliferation, which is completed by around postnatal day 15 in rats and before puberty in humans. Treatment
beginning at a later time relative to the window for Sertoli cell proliferation or for a longer duration is not expected to
have additional adverse effect as the effect was not shown to be degenerative. Birth Defects Res (Part B) 92:304–313,
2011.
Changes induced by treatment with aromatase inhibitors in testicular Leydig cells of rats and dogs. - PubMed - NCBI
Changes induced by treatment with aromatase inhibitors in testicular Leydig cells of rats and dogs.
Treatment of male rats and dogs with CGP 32,349 (formestane), a steroidal aromatase inhibitor, and CGS 20,267 (letrozole), a non-steroidal aromatase inhibitor, induced different alterations in testicular interstitial Leydig cells in the two species. Whereas in dogs Leydig cells were hypertrophic and hyperplastic, in rats either no effect (CGS 20,267) or atrophy of Leydig cells (CGP 32,349) was reported. The different response of the two species can be explained by different regulating mechanisms of gonadotropin secretion by the anterior pituitary.
Testis morphology in rats chronically treated with letrozole, an aromatase inhibitor. - PubMed - NCBI
Testis morphology in rats chronically treated with letrozole, an aromatase inhibitor.
The aim of this study was to investigate the influence of the long-term treatment of rats with letrozole on the testis morphology. The pharmacologically induced estrogen deficiency caused statistically significant decreases of both intratesticular and serum levels of estradiol, and morphological changes in the seminiferous epithelium and in the interstitial tissue of the testes. Six months of treatment resulted in the sloughing of premature germ cells of the seminiferous epithelium into the tubular lumen and in intraepithelial vacuolization. Multinucleated giant cells composed of premature germ cells, conglomerates of various cell nuclei and cell debris as well as irregularities and infoldings of the tubular basement membrane were also seen. Moreover, deep invaginations of the lamina propria with myoid cells were observed. Cells in the interstitial tissue showed changes similar to that observed in aging processes. The cytoplasm of LH-R-positive Leydig cells was loaded with lipofuscin granule( so aged testis essentially ? ?
). The number of lipofuscin-loaded cells was significantly increased in the interstitial tissue of testis in letrozole-treated rats. The results indicate the direct influence of estrogens on seminiferous tubules and the interstitial tissue morphology.https://onlinelibrary.wiley.com/doi/pdf/10.2164/jandrol.05195
Reducing Estrogen Synthesis in Developing Boars Increases Testis Size and Total Sperm Production
"Testes of aromatase-inhibited boars initially exhibited delayed lumen formation, lower testicular weight, fewer detergentresistant spermatids, and fewer Sertoli cells, but by 7 to 8 months, these boars had recovered and had larger testes, more detergentresistant spermatids per testis, and more Sertoli cells. Total Leydig cell volume increased in proportion to testis size. Reducing endogenous estrogen is consistent with a delay in testicular maturation/puberty that allows for a longer window for the proliferation of Sertoli cells and maturation of Leydig cells, resulting in larger testes and higher spermatid production."
P450-aromatase activity and expression in human testicular tissues with severe spermatogenic failure. - PubMed - NCBI
P450-aromatase activity and expression in human testicular tissues with severe spermatogenic failure.
There is evidence that impaired spermatogenesis is associated with an imbalance in the oestradiol/testosterone ratio and with Leydig cell (LC) dysfunction. In testis, P450-aromatase, encoded by CYP19, is responsible for the conversion of testosterone to oestradiol. The aims of this study were to quantify CYP19 mRNA expression, aromatase activity and protein localization, and to measure the oestradiol to testosterone ratio in testicular tissues of men with spermatogenic impairment. Twenty-four men with complete Sertoli cell-only syndrome (SCOS), 14 with focal SCOS, 14 with maturation arrest (MA), 8 with mixed atrophy and 30 controls with normal spermatogenesis were subjected to testicular biopsy. All subjects underwent a physical examination, cytogenetic and serum hormonal studies. Testicular CYP19 mRNA was quantified using real time RT-PCR. Testicular aromatase activity was measured using the (3)H(2)0 assay and protein expression was evaluated using immunohistochemistry. In cases, serum testosterone and oestradiol were normal, but the testosterone/LH ratio was lower compared with controls (p < 0.05). Aromatase was localized in the Leydig, Sertoli and germ cells of all tissues, although stronger intensity was observed in LC. Aromatase mRNA and activity were not altered in cases and correlated positively with LC number (r = 0.516 and r = 0.369; p < 0.008). The intratesticular oestradiol/testosterone ratio was elevated (p = 0.005) in complete SCOS patients compared with controls. In conclusion, testicular aromatase seems to be normal in most subjects with impaired spermatogenesis. However, an altered intratesticular oestradiol/testosterone ratio in some patients with complete SCOS suggests that aromatase is increased, which might contribute to Leydig cell dysfunction.
https://academic.oup.com/biolreprod/article/81/Suppl_1/19/2955088
Sertoli Cell Numbers Increase Rapidly After Aromatase Inhibition in Young Boars.
tldr; AI-treated young boars have bigger testis and more sertoli cells
https://www.researchgate.net/publication/7599892_Reducing_Estrogen_Synthesis_Does_Not_Affect_Gonadotropin_Secretion_in_the_Developing_Boar
tldr; Treatment with the aromatase inhibitor reduced testicular aromatase activity by 90% and decreased E2 and ECs without changing acute, long-term, or postcastration LH and FSH. Plasma T, testicular T, and circulating INH concentrations did not change. Testicular INH was elevated in treated boars compared with controls. In conclusion, estrogen does not appear to play a regulatory role on gonadotropin secretion in the developing boar. This is in direct contrast to findings in males of several other species (maybe this explains different results on different animals w/ AI treatment thinking_emoji)
https://www.sciencedirect.com/science/article/pii/S0016648016300442
Effect of Letrozole, a selective aromatase inhibitor, on testicular activities in adult mice: Both in vivo and in vitro study
Letrozole suppresses spermatogenesis by reducing insulin sensitivity and glucosetransport in the testis. Decreased insulin sensitivity inhibits the glucose transport in the testis by suppressing GLUT8.
ill limit the studies to these ones for now. i wish i had more negative studies but this is what i have so far.
in actual human trials, the effects of AIs seem mostly positive in males. females idk so much.
~comments welcome~
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