Associations of vitamin D status and vitamin D-related polymorphisms with sex hormones in older men
Highlights
• Vitamin D might influence sex hormone and gonadotropin levels.
• Lower vitamin D status is associated with lower testosterone levels.
• There was no association between gene polymorphisms and sex hormone levels.
https://www.sciencedirect.com/science/article/abs/pii/S0960076015301394
Highlights
• We examined the relationship between vitamin D and sex hormone levels among men and women.
• Low vitamin D was associated with lower sex hormone binding globulin and higher free testosterone levels in men and women.
• Low vitamin D levels was associated with lower estradiol and higher dehydroepiandrosterone levels in women.
• These associations between vitamin D and sex hormones were independent of adiposity and lifestyle.
• Future research is needed to determine whether vitamin D treatment influences sex hormone levels.
https://www.sciencedirect.com/science/article/abs/pii/S0378512216303917
Vitamin D and sex steroid production in men with normal or impaired Leydig cell function
Highlights:
• Young men with vitamin D deficiency have lower testosterone/estradiol ratio
• Men with impaired Leydig cell function and vitamin D deficient are less sensitive to hCG stimulation
• Testicular tissue culture exposed to calcitriol induces a significant increase in testosterone
• Vitamin D may have a stimulatory role on androgen production in men
https://www.sciencedirect.com/science/article/abs/pii/S0960076019305680
I find this one also interesting, as the outcome of HCG treatment in PFS patients varies a lot. I wonder if this has an association to impaired Leydig cells and low vitamin D levles.
This may be a bit off but a little piece of the puzzle. Vitamin D seems to be able to increase the 3β-hydroxysteroid dehydrogenase activity https://www.sciencedirect.com/science/article/abs/pii/S0960076018306435
Also somewhat off: Vitamin D improves vaginal dryness in postmenopausal women. PFS seems to be some male pendant. So maybe this would would also improve the dryness of the glans penis:
We found a trend towards increased risk of hypogonadism in men within the lowest 25(OH)D quintile (≤43.9 nmol/L). In conclusion, our data suggest that men with very high 25(OH)D levels (>102 nmol/L) might be at an increased risk of hypogonadism. Furthermore, we observed a trend towards increased risk of hypogonadism in men with very low vitamin D levels indicating a U-shaped association of vitamin D levels and hypogonadism. With respect to risk of male hypogonadism, our results suggest optimal serum 25(OH)D concentrations of 82-102 nmol/L.
This, in my opinion my explain why some guys do well on vitamin D, but when they overdo it they may in up in a crash. Me myself I felt some overall improvements, but I also had terribly low vitamin D although I try to get as much sun as possible.
" Thus, it can be concluded that vitamin D3 delays testicular senescence by regulating proliferation and apoptosis."
https://www.nature.com/articles/s41598-019-50679-y
“The testes of vit. D-deficient rats showed incomplete spermatogenesis and degenerative changes. Although interpretation is complicated by the intricate communication among testis cell types, these data suggest that the Sertoli cell is a primary site of action of 1,25(OH)2D in the testis. Moreover, these data indicate that 1,25(OH)2D receptor function in the testis relates to germ cell division/maturation, although this may be an indirect effect via the Sertoli cells.”
https://www.sciencedirect.com/science/article/abs/pii/0022473189901052
“Vitamin D may have a stimulatory role on androgen production in men”
https://www.sciencedirect.com/science/article/abs/pii/S0960076019305680
" Epidemiological data have shown that vitamin-D deficiency is also associated with erectile dysfunction. In this review, our aim is to interpret the mechanisms by which vitamin-D might regulate anatomy and physiology of penis. Evidence showed that vitamin-D is needed for an adequate erectile function"
An extra mechanism of VD on erectile function seems to function via binding to T receptors. Computer ( in silico ) modeling shows that besides activating the VDR, 1,25-D displays high affinity for some of the body’s other nuclear receptors. This suggests that when 1,25-D increases above its normal range, it binds the α/β thyroid, the glucocorticoid, and the T receptors, displacing their native ligands [53]. Marshall [54] showed the symmetry with which endogenous ligands exhibited very similar affinities across some members of the type 1 nuclear receptor family [54]. For example, 1,25-D docked into the VDR with a (nanomolar) Kd of 8.48, but also exhibited a Kd of 8.05 into the T receptor.
VD is positively associated with T, exhibits a concordant seasonal changeability [47], elevates when T was supplemented in hypogonadism [48]. Surprisingly, the reverse situation is also true, suggesting that VD supplementation might increase T levels [49]. In a clinical randomized controlled trial, which is the first on this topic in literature, Pilz et al [49] investigated the effect of VD supplementation on androgens in men. The results were significant and the researchers observed that overweight men with VDD had a clinically meaningful increase in serum T levels after VD supplementation for 1 year [49]. Recently, it was also demonstrated that VD supplementation improves T levels, metabolic syndrome and erectile function in middle-aged VD deficient men [8]. Canguven
Here’s a thread compiling various users’ Vitamin D levels:
I calculated these:
Here’s an article about what a normal Vitamin D level should be. Different experts have different recommendations:
Vitamin D: What’s the “right” level? from Harvard Health Blog
https://www.health.harvard.edu/blog/vitamin-d-whats-right-level-2016121910893The majority of folks have a level between 20 and 40, in my experience, and this is corroborated by the IOM’s findings in that 2010 report.
Endocrine Society: "Based on all the evidence, at a minimum, we recommend vitamin D levels of 30 ng/mL, and because of the vagaries of some of the assays, to guarantee sufficiency, we recommend between 40 and 60 ng/mL for both children and adults.”
According to a NEJM article, “a more appropriate cutoff for vitamin D deficiency would be much lower, 12.5 ng/mL.”
Based on all the above, it’s not clear those levels reported from Forum users are in fact low.
The papers you posted point to a potential connection of Vitamin D and hypogonadism, but I’m not sure they establish whether Vitamin D is a real cause or risk factor for hypogonadism (I’ve only looked at abstracts).
In aging and hypogonadism (or any systemic disease) we can expect that many chemicals and systems are not at optimal levels/functioning. So when we see just one of them out of range, we don’t know if it has a causal role. Is it a symptom or a cause?
The more I look into the literature, the more it seems the post-finasteride condition could be a breakdown in the system’s ability to maintain equilibrium (‘androgenic system failure’ for short?). For example Vitamin D deficiency could be both a symptom and a cause. (Even the concepts of cause and effect are too simplistic.)
Why do you think the levels in the forum are normal? 40-60 is healthy, 82-102 is optimal for optimal testosterone levels.
The problem with the “normal range” is that it the normal range includes everyone who is 50, 60, 70, 80… as vitamin D levels go down with age they affect the statistics and what is “normal”. I didn’t find age-matched vitamin D levels but I am 99% sure that the mean 22 value of the forum is incredibly low.
And yes, vitamind D affects androgene levels. And yes, it seems that even the testes is involved in the vitamin D production. Vitamin D is important for the production of healthy sperm cells.
And yes, I believe both is affecting each other.
I think you are right, the whole feedback loop system in PFS is broken - there is no equilibrium, some metabolites are missing where they are needed for production of healthy sperm or protection of the brain. The closed comparison I think is the menopause in many ways. Although I think in menopause some tissues like the brain will still produce important neurosteroids and thus women won’t be affected as much as PFS patients.
Here’s another study that finds a Vitamin D <-> hypogonadism link:
Conclusions: Secondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation.
You’re making a few claims that I can’t evaluate:
Vitamin D level of 40-60 is healthy, 82-102 is optimal for optimal testosterone levels.
Most of the authorities quoted in the Harvard Health Blog article do not agree with this range.
Vitamin D levels go down with age.
Do you have a citation on the expected normal range for young men?
Vitamin D affects androgen levels.
Where is the evidence of a causal role? Most of the papers you’ve posted call it an association and don’t claim a causal role.
[deleted]
This is goofy. I was under the impression medicine quit using elderly and ill people to establish “healthy” reference ranges after the similar controversy surrounding testosterone levels? I hope this is corrected in the future.
25(OH)Vitamin D3 (Calcidiol) is degraded by an enzyme called 24-hydroxylase (CYP24A1). Stolzt and others have found that CYP24A1 is under control of androgen signaling:
To summarize, our results demonstrate that androgen (DHT) signaling controls 24-hydroxylase degradation by regulating Pgr expression at the transcriptional and translational levels (Fig. 6B).
We have demonstrated that DHT [negatively] regulates the induction of 24-hydroxylase mRNA levels. (Stolzt, 2006)
androgen deficiency within renal function acts to enhance 24-hydroxylase expression and suppresses the actions of vitamin D
These findings uncover an important role for androgen in vitamin D homeostasis
These papers have clearly laid out that Vitamin D3 levels are positively driven by AR signaling through negative regulation of CYP24A1. In other words, low AR signaling will result in low Vitamin D3 levels.
It is well documented in this forum that PFS patients often present with low Vitamin D3 levels. This is one of many smoking guns which point to a deregulated AR signal in PFS patients, as do low 3a-diol-G, deregulated T, LH, FSH and estradiol, for the same reason.
If it increasingly becomes recognized that PSSD and PAS patients are presenting with similar hormonal abnormalities, this alone should be enough proof imo that we have a likely common denominator here at the AR level.
Any thinking on the fact that autoimmune patients also have low vitamin D?
Autoimmune disease represents a class comprised of over 80 different disorders. Which one specifically are you referring to? I can only assume that you are talking about what @anon5006275 stated above:
I am not clear on what the basis of this statement and diagnosis is.
To answer your question, maybe you need to take a different angle. AR deregulation has been shown to play a key role in modulating immune response and auto-immune disorders:
Altogether, androgen/AR plays distinct roles in individual immune cells, and targeting androgen/AR may help in treatment and management of immune-related diseases.
So given that AR deregulation seems to be key in immune-related diseases, it would make a lot of sense that Vit D3 will also will be deregulated, given what I cited in my previous post. Imo it makes more sense that changes in immune response with PFS patients are a manifestation of AR deregulation rather than have any role at the root cause level.
https://www.sciencedirect.com/science/article/pii/S0002944012005731
@awor if it’s dependent on androgen signaling why did I have near 0 levels of vitamin D before I even took propecia and I still had an above average sex drive and no symptoms of low androgens?
Maybe another survey might work here…I have used SP+ accutane never had low vitD test results…
The AR mediated pathway I cited is involved in degradation, as mentioned. The other side of the story is the production and metabolism one. Enzymes such as CYP2R1 and CYP27B1 are involved there. Furthermore, skin and organs such as kidneys are also involved in the supply side of Vitamin D forms. The whole process frankly is quite complex, and I cannot tell you why you had low Vit D3 levels pre PFS. Have you ever asked a doctor? Having said this, Vitamin D deficiency is quite common, due to lifestyle (i.e. lack of sun exposure) and for other reasons. As I said, Vit D3 deregulation is just one of many smoking guns, there are many more:
Source please! Thanks.
In addition to what’s been written: Recently we published a document which included a detailed and fully cited outline of how overexpression of the AR mechanistically recapitulates the effects of polyglutamine expanded AR, which underlies the broad symptoms of SBMA.
In SBMA, serum low vitamin D is also a very frequent finding (Querin et al., 2015). During our work, the staff collated all existing PFS patient reports of serum vitamin D levels. The reported values in our cohort are often also low. Given this is an observed effect in a disease state recapitulated by WT-AR amplification, this would support that vitamin D levels would frequently be low in PFS.
It is of note that other frequently reported serum findings in SBMA, including elevated metabolic markers (total cholesterol, triglycerides, fasting glucose and insulin etc) and creatine kinase are also well reported in PFS patient anecdotes. Like in SBMA, these are heterogeneous and not frequent to the extent of a determinable biomarker.