I actually tried using bovine ovaries from Swanson myself for over a year. The idea behind it is to stimulate aromatase activity, enabling the conversion of testosterone into estrogen. Of course, this only works if you still have your testicles. Personally, I didn’t notice any significant changes, but I also wasn’t doing regular blood monitoring. That said, there are people who report noticeable effects, so it seems to work for some—especially at relatively high doses.
Whether the effect is permanent, I can’t say for sure, but according to the manufacturer, it should be. After Brexit, though, it became really difficult to get hold of the product, as it was constantly sold out and quite expensive. That’s ultimately why I stopped using it.
03.05.2025 22:42:04 Zoe Vee via groups.io <stephenie.vee@...>:
Well that's kind of a bummer. Or is there a way to get my brain into producing those neuroestrogens?
Seems there is positive effect of estradiol produced specifically in the brain, not just systemic estradiol in blood. In this case, the effect is on appetite control. For this to work (at least in the mouse model), you need to have aromatase working, and to have feedstock, which is testosterone. This action is not duplicated with just blood estradiol.
Estrogen synthesized in the central nervous system enhances MC4R expression and reduces food intake
Estrogen is synthesized throughout various tissues in the body, and its production is regulated by the rate-limiting enzyme aromatase (encoded by the Cyp19a1 gene). Notably, aromatase is also expressed in central nervous system cells, allowing for localized estrogen synthesis in regions such as the hypothalamus. Estrogens produced within these neurons are referred to as neuroestrogens. In this study, we investigated the role of neuroestrogens in the regulation of appetite through modulation of hypothalamic pathways in OVX, ArKO, and aromatase-restored mice. Estrogen suppresses appetite by influencing the expression of appetite-regulating peptides, including POMC and NPY, via MC4R. We explored the direct effects of neuroestrogens, independent from ovarian estrogen, on appetite suppression and the underlying molecular mechanisms. We monitored body weight and food intake and evaluated the expression of Cyp19a1, Mc4r, and other appetite-related genes. Our findings indicate that OVX and ArKO mice exhibited increased body weight and food consumption, which correlated with altered expression of Mc4r and Cyp19a1. Conversely, restoration of Cyp19a1 expression in a neuron specific manner significantly decreased food intake and increased Mc4r expression in the hypothalamus. Furthermore, neuroestrogens enhanced leptin responsiveness. Our results imply that neuroestrogens likely contribute to appetite regulation and may be relevant for body weight reduction.
Introduction This paper is dedicated with heartfelt gratitude to Dr. Seymour (Si) Reichlin whose mentorship during a fellowship in neuroendocrinology at Tufts (1987–1988) continues to inform my career. For neurologists such as myself, the scope of clinical neuroendocrinology broadens significantly when considering the pervasive influences of circulating gonadal hormones on neurological disease expression. This article examines the diverse range of central and peripheral nervous system disorders affected by reproductive hormone fluctuations. The review focuses predominantly on steroid–neural interactions in women, given that the relatively stable (tonic) pattern of androgen secretion in men makes it more challenging to delineate the roles of testicular hormones in the natural history of neurological disorders.
Hormonal changes associated with specific stages of the menstrual cycle, pregnancy, menopause, and exposure to exogenous sex hormones can impact the release and metabolism of neurotransmitters and neuromodulators, potentially triggering or altering the semiology of various neurological and neuropsychiatric conditions. This review covers the major categories of human neurological disease—vascular, metabolic, inflammatory, degenerative, and others—with emphasis on how these conditions manifest in women. Neurological disorders that respond to specific hormonal and antihormonal therapies are highlighted. The involvement of gonadal hormones in psychiatric conditions such as depression, psychosis, and premenstrual syndrome is covered in other sources (1).
"Ageing impairs the ability of neural stem cells (NSCs) to transition from quiescence to proliferation in the adult mammalian brain. Functional decline of NSCs results in the decreased production of new neurons and defective regeneration following injury during ageing1,2,3,4. Several genetic interventions have been found to ameliorate old brain function5,6,7,8, but systematic functional testing of genes in old NSCs—and more generally in old cells—has not been done. Here we develop in vitro and in vivo high-throughput CRISPR–Cas9 screening platforms to systematically uncover gene knockouts that boost NSC activation in old mice. Our genome-wide screens in primary cultures of young and old NSCs uncovered more than 300 gene knockouts that specifically restore the activation of old NSCs. The top gene knockouts are involved in cilium organization and glucose import. We also establish a scalable CRISPR–Cas9 screening platform in vivo, which identified 24 gene knockouts that boost NSC activation and the production of new neurons in old brains. Notably, the knockout of Slc2a4, which encodes the GLUT4 glucose transporter, is a top intervention that improves the function of old NSCs. Glucose uptake increases in NSCs during ageing, and transient glucose starvation restores the ability of old NSCs to activate. Thus, an increase in glucose uptake may contribute to the decline in NSC activation with age. Our work provides scalable platforms to systematically identify genetic interventions that boost the function of old NSCs, including in vivo, with important implications for countering regenerative decline during ageing."
"Estradiol is the most potent and ubiquitous member of a class of steroid hormones called estrogens. Fetuses and newborns are exposed to estradiol derived from their mother, their own gonads, and synthesized locally in their brains. Receptors for estradiol are nuclear transcription factors that regulate gene expression but also have actions at the membrane, including activation of signal transduction pathways. The developing brain expresses high levels of receptors for estradiol. The actions of estradiol on developing brain are generally permanent and range from establishment of sex differences to pervasive trophic and neuroprotective effects. Cellular end points mediated by estradiol include the following: 1) apoptosis, with estradiol preventing it in some regions but promoting it in others; 2) synaptogenesis, again estradiol promotes in some regions and inhibits in others; and 3) morphometry of neurons and astrocytes. Estradiol also impacts cellular physiology by modulating calcium handling, immediate-early-gene expression, and kinase activity. The specific mechanisms of estradiol action permanently impacting the brain are regionally specific and often involve neuronal/glial cross-talk. The introduction of endocrine disrupting compounds into the environment that mimic or alter the actions of estradiol has generated considerable concern, and the developing brain is a particularly sensitive target. Prostaglandins, glutamate, GABA, granulin, and focal adhesion kinase are among the signaling molecules co-opted by estradiol to differentiate male from female brains, but much remains to be learned. Only by understanding completely the mechanisms and impact of estradiol action on the developing brain can we also understand when these processes go awry."
Yes. This paper further supports that not E2's, and in small doses, are useless for the brain. At least here the evidence is for preparing, which is E1 and E1S primarily, and so you do get E2 out of that, but in very small quantities. I'm still curious about the effect of small dose "female normal" levels of testosterone on the brain. The theory of course is that estradiol is the primary brain sex hormone, and T is just a link in the chain. But there still is no conclusive study on the subject. If it makes a difference, and for who. The brain does have AR receptors, and they do do something. I'd be curious to know what.
"...Further, more than 80% of females who underwent PBO at all ages used ERT; adjusting for ERT use did not affect the associations. Notably, the females in the current cohort would have been prescribed conjugated equine estrogens based on the years of PBO and transition through menopause for referents. It is not known whether other hormone regimens such as transdermal 17?-estradiol would have affected white matter integrity differently..."
Besides differences between Premarin and estradol, doctors' gospels preach about ERT: "dosage the less the better, stop as soon as possible".
Sufficiently advanced incompetence is indistinguishable from malice.
INTRODUCTION Premenopausal bilateral oophorectomy (PBO) is associated with later-life cognition, but the underlying brain changes remain unclear. We assessed the impact of PBO and PBO age on white matter integrity.
METHODS Female participants with regional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA) and mean diffusivity (MD) were included (22 with PBO < 40 years; 43 with PBO 40-45 years; 39 with PBO 46-49 years; 907 referents without PBO < 50 years). Linear regression models adjusted for age and apolipoprotein E (APOE) genotype.
RESULTS Females with PBO < 40 years, compared to referents, had lower FA and higher MD in the anterior corona radiata, genu of the corpus collosum, inferior fronto-occipital fasciculus, superior occipital, and superior temporal white matter. Females who underwent PBO between 45 and 49 also had some changes in white matter integrity.
DISCUSSION Females who underwent PBO < 40 years had reduced white matter integrity across multiple regions in later-life. These results are important for females considering PBO for noncancerous conditions.
Highlights Females with premenopausal bilateral oophorectomy (PBO) < 40 years had lower FA versus referents. Females with PBO < 40 years had higher MD in many regions versus referents. Adjusting for estrogen replacement therapy use did not attenuate results. Females with PBO 45-49 years also had some white matter changes versus referents.
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My takeaway key point here is:
"...Further, more than 80% of females who underwent PBO at all ages used ERT; adjusting for ERT use did not affect the associations. Notably, the females in the current cohort would have been prescribed conjugated equine estrogens based on the years of PBO and transition through menopause for referents. It is not known whether other hormone regimens such as transdermal 17β-estradiol would have affected white matter integrity differently..."
A chemical signal in human female tears lowers aggression in males
"Mammals use various bodily media to convey social chemical signals. For example, human social chemosignaling research has focused on sweat [1], and rodent research has focused on urine [2]. Social chemosignaling, however, also extends to media such as feces [3], milk [4], and tears [5–12]. Rodent tear signaling has been studied in 2 contexts: reproduction and aggression. In reproduction, a male-specific peptide secreted from the extraorbital lacrimal gland, named exocrine gland-secreting peptide 1 (ESP1), is transduced by female V2Rp5-expressing vomeronasal sensory neurons [5]. This triggers signals from the accessory olfactory bulb to hypothalamic and amygdaloid nuclei, which enhance female sexual receptive behavior [6]. The tear-bound signal ESP1 is also the primary signal in the Bruce effect, where a pregnant mouse will miscarry upon perceiving an ESP1 signal from a male who did not father the pregnancy [7]. These tear-bound signals function not only within species but also across species: Like ESP1 in mice, rat cystatin-related protein 1 (ratCRP1) is released from male rat tears and alters behavior in female rats. This same rat signal, however, also triggers predator avoidance in mice [9]. Beyond reproductive signaling, a primary domain for rodent tear signaling is aggression. The above noted tear signal ESP1 that promotes sexual behavior in females also increases aggressive behavior in males smelling their own ESP1 secretions [8]. However, most aggression-related tear signaling appears to block rather than promote aggression. This was first identified in blind mole rats, where subordinate males cover themselves in tears to reduce dominant male aggression toward them [10]. Similarly, mice pups emit in their tears exocrine gland-secreting peptide 22, which through a vomeronasal accessory olfactory pathway, reduces male sexual aggression toward them [11]. Finally, female mouse tear liquid contains signals that abolish intermale aggression by modulation of activity in aggression brain networks [12]. In contrast to this extensive body of research into rodent tear chemosignaling, there is only limited evidence for human tear chemosignaling. Human female tears contain a perceptually odorless chemical signal that when sniffed, lowers testosterone in human males [13,14], but the behavioral significance of this effect remains poorly understood. More specifically, one study found that sniffing tears drove a small but significant reduction in ratings of sexual arousal attributed to pictures [13], and the second study observed that despite significantly lowering testosterone, sniffing tears did not affect appetite [14]. Given that reduced male testosterone is associated with reduced male aggression [15], here, we set out to test the hypothesis that like in rodents, human tears contain a chemical signal that blocks aggression. Notably, there are indeed several instances of chemical signals altering hormonal-dependent behavior in humans [16]. Examples include maternal behavior [17,18], ingestive behavior [19,20], social behavior in general [21,22], and sociosexual behavior in particular [23–25]. In other words, that a chemical signal can alter human behavior is not unusual. Moreover, particularly emotional behaviors are a prime candidate for modulation by chemical signals [26], possibly a reflection of their shared neural substrates in the amygdaloid complex [27,28] and an extensive associated brain network spanning ventral temporal cortex, frontal cortex, anterior cingulate cortex, and insula striatum [29]. Given this neural link, and that human aggression can be measured behaviorally using various standardized tasks [30], we set out to measure the aggressive behavioral and brain response following sniffing emotional tears."
"Few"... so there are differences, it's just semantics. Eliot didn't disprove anything, just doesn't like the idea that women might be biologically different - "inferior" - than men. What about she eats a cookie with a lethal dose of poison in it? It wouldn't matter, it's practically all just a cookie, what can be the contribution of the poison...
"Generally, a negative feedback relationship exists between testosterone and LH. However, this relationship may not be accurate in aging men. Several studies, including this study, consistently show LH increasing as a function of age in elderly men. Furthermore, increasing evidence indicates that LH may not be correlated with testosterone in aging men, which is consistent with our findings."
I think that this article authors' interpretation of their statistics is stupid. If you give (inject) those old men enough testosterone, LH will not be high. Different men have different sensitivity to testosterone, different thresholds of testosterone level when pituitary produces LH trying to increase testosterone production by testicles. When testosterone level and as a consequence level of estradiol produced by aromatase from testosterone is not enough high for hypothalamus and pituitary, likely these levels are not enough for the rest of the brain too, resulting in cognitive impairment / dementia.
If an old man has high LH, that's a sign that his testosterone level is not enough for him (because his testicles cannot produce enough testosterone). Or rather not enough (for him) estradiol produced by aromatase from testosterone.
I fully agree with this, have had the same happen although have noticed my stress has gone up in recent times and my drinking has followed up as well even though I'd totally given it up a year prior and restarted due to stress as well, whereas pre HRT I was drinking due to my hormone imbalance (the want for alcohol, pot or tobacco hasn't come back since starting hrt but it seems that stress does trigger my use of things, do have a vape but don't buy tobacco any more and not constantly tied to it either),
