Blocking FSH May Reduce Body Fat Levels and Increase Bone Density In Menopause

A new mechanism for treating obesity and bone loss in menopause?

Introduction

I have previously discussed how brown fat and beige fat may actually be important in helping us to control our weight and reduce overall body fat levels.

FSH is a pituitary hormone.

You can read my post on the subject here.

Regular “white” fat cells store energy and aren’t very active.

On the other hand brown and beige fat cells use a lot of energy at rest and can help to use up stored fat.

They seem to be important for thermogenesis (heat production) and certain techniques such as controlled exposure to cold temperatures (e.g. cold showers) may increase levels of these fat types.

A new study in Nature by Liu et al [1] suggests that blocking a hormone (FSH) using an antibody may increase the levels of beige/brown fat (fat browning) and may also increase bone mass.

The Idea Behind this Study

FSH (Follicular Stimulating Hormone) is a pituitary hormone that has a number of functions relating to sexual function. There is a nice summary on the Wikipedia page.

FSH rises around menopause.
Amongst these effects is a relationship to the levels of sex hormones with a feedback loop — so if sex hormone levels fall, FSH levels rise to bring them back up.

It appears that as women enter menopause and their oestrogen levels fall the levels of FSH rise in order to try to stimulate more ovarian production of this type of hormone.

Since the ovaries are no longer active this doesn’t work so the levels of FSH stay high (there is no increase in oestrogen levels to feedback and normalise the FSH).

“Previous human studies and particularly the Study of Women’s Health Across the Nation (SWAN), an observational cohort of pre-, peri- and postmenopausal women followed for a decade, have suggested that a phase of rapid bone loss ensues two to three years before the onset of menopause, when FSH levels are rising and oestrogen levels are relatively stable.
Furthermore, even after the onset of menopause, oestrogen replacement therapy does not always suppress serum FSH levels into the premenopausal range, and women often continue to lose bone and further accrue visceral fat.”
Menopause can result in decreased bone density and increased fat levels.

So, the authors of this study were basically wondering if these effects might in some way be related directly to the raised levels of FSH.

They decided to test this by creating an antibody which blocks it.

They then carried out a number of studies in mice to see what effects the antibody would have.

A number of different methods were used to confirm this and I would suggest reading the paper for the detailed information as there is just too much to cover here.

Unfortunately the paper is not open access and I don’t want to get in trouble for posting too much specific information.

(Lack of open access is a topic I have previously discussed a couple of times and you can read more here.


The Findings

Overall from the multiple experiments that were done, there were 2 main findings.

White fat cells.

Blocking FSH using the antibody:

  1. Reduced fat levels with a corresponding increase in beige fat tissue.
  2. Increased bone mass.
So it does seem that blocking FSH increases browning of white fat (the conversion of white fat into brown/beige fat) and it also seems to increase bone density.

Problems

As always there are problems with this kind of research:

Can these results be replicated in humans?
  1. Tiny sample sizes — this is often the case in studies of this sort and in this case the samples vary from 2–5 mice.
  2. Mice are not humans.
  3. Unforeseen consequences of FSH blockade.
  4. Application to males?
  5. Other Issues.

1) Tiny Sample Sizes

The tiny sample sizes are an obvious problem that we encounter quite regularly in this kind of biological research.

Tiny is not good when it comes to sample sizes.

Unless we get further confirmation with larger sample sizes we cannot be sure that there were not anomalies or oddities in the particular mice that were used here.

2) Mice Are Not Humans

Mice are not humans. Basically just because something works in mice does not necessarily mean it works in humans.

Mice are Not Humans.

This has been especially true with previous research regarding obesity — for example the hormone leptin seemed to initially suggest an effective target for treating obesity in mice studies but it never really seemed to work the same way in humans.

This is a common issue. Over time and in different species the effects and relationships of certain hormones can change and become subtly modified.

It may be that something similar applies to FSH in humans. The only way to know for sure would be to test an FSH antibody in humans.

3) Unforeseen/Unknown Effects

In view of the above there may also be unforeseen consequences of FSH suppression in menopausal woman that we don’t yet understand.

Unforeseen consequences?
This is one of the things that people often lose sight of when there is excitement over a new finding.

4) Application to Males?

In some of the tests here both male and female mice were used and it seems the effects applied to both.

Is this useful for men?

This may be a problem in humans though. Although sex hormone levels in men fall with age too, there is no definite “menopause” such as that which occurs in women.

It is not clear what the actual effect would be of FSH blockade in human male subjects.

I don’t think men would be happy to have their testosterone or other androgen release potentially suppressed as a means to lose weight.

Further the authors themselves cite previous research that suggests that androgens themselves may have a browning affect on white fat.

Suppression of androgen release by FSH blockade may therefore be counterproductive in men.

To be fair the main suggestion in this paper is to use the technique in menopausal women though. As always further understanding of the mechanisms at play here may help to clarify these issues.

5) Other Issues?

Another point I found interesting and which was only briefly covered was that there did not appear to be corresponding changes to other metabolic markers like blood glucose and blood lipids despite the increases in fat browning.

Glucose and lipid levels unaffected?

This is not consistent with previous research I have read but it is hard to say how relevant this is in such a small study.

It could be related to the major issues of small sample size and inability to transfer animal results to humans, or it could be due to some other reason.


Conclusion

This is certainly interesting preliminary research. I think the role of FSH in obesity and metabolic syndromes may well turn out to be greater than had previously been presumed.

Could FSH teach us more about the mechanisms of obesity?

The problem is that we won’t really know more until we get some replication of these results in humans.

That will take time and there are a variety of issues. First of all more animal studies will need to be done.

Tiny sample sizes mean that we can’t read too much into what is presented here without actual replication.

Even then there will be ethical and safety hurdles as we do not know for sure what the effects of FSH blockade would be in otherwise “healthy” post-menopausal women.

The question of whether this could be used in men too is also still up for debate.

If it does pan out the potential for new treatments based on this are great.

As the authors state in their discussion:

“A humanized Hf2 or its equivalent may not only be efficacious in reducing visceral and subcutaneous fat in people, but might also provide benefit for certain medical conditions associated with visceral adiposity, such as metabolic syndrome, cardiovascular disease, cancer, diabetes, and polycystic ovarian syndrome.”

Previous anti-obesity drugs have been pretty lacklustre in their results and in many cases they have major side effects.

A potentially safe drug without long term negative effects would be a huge advancement, even if it could only be used in menopausal women.


References

  1. Liu, Peng, Yaoting Ji, Tony Yuen, Elizabeth Rendina-Ruedy, Victoria E. DeMambro, Samarth Dhawan, Wahid Abu-Amer, et al. 2017. “Blocking FSH Induces Thermogenic Adipose Tissue and Reduces Body Fat.” Nature 546 (7656): 107–12.

Thank you for reading


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