This week’s wonder-full paper and light-bulb discovery was prompted by a 34 year old woman with a history of Depo Provera injections over several years to control unruly menstrual bleeding and pain. She was subsequently diagnosed at 28 with osteoporosis. That’s not a mispelling…not -penia, -porosis. Now I may be a bit slower than some on the ol’ synthetic hormone fallout front but when it was pointed out that this is a known possible side effect of this synthetic progestin (even features in the consumer brochure), which is used for a range of indications in both pre and post-menopausal women, I did a double-take. What kind of progesterone replacement impacts your bone health negatively and how? And therein the real trouble started.
So fixated are we (myself included) on the evils of oestrogen, I think we’ve failed to notice the wolf in sheep’s clothing that can be synthetic progestins for some patients. Not just in general terms of concern regarding all synthetic hormones but as a result specifically of their interaction with glucocorticoid receptors (GR). This excellent paper reviews this aspect of the 2 most commonly used ones: medroxyprogesterone acetate (MPA) and norethisterone enanthate.
The bottom-line? MPA (which is Depo provera) is a significant GR agonist. That means it’s behaving like cortisol producing a degree of immune suppression and constituting yet another mechanism, in addition to the low oestrogen state it induces, by which negative bone effects may be mediated. This is not a mild or minor action according to this and other research. This is likely to have significant implications for some women, including this 34 year old female. Some women see reversal of this demineralisation following cessation, but not all and the younger your first exposure, the higher the likelihood it won’t correct. This woman had other osteoporotic risk factors, sure, but never enough on their own to produce such severity so young. Mind. Blown.🎆 Or is that just me?
While none of us are likely to be advocating for replacement sex hormones without very careful consideration, this has really helped me to change channels off my oestrogen obsession and become alert to the potential for broader effects from synthetic progestins. MPA…you’re firmly on my radar now in a whole new way.
As always, our patients teach us the most and thanks to Amanda Mullemeister for bringing hers to our recent mentoring session. The learning is never one-directional and I am so privileged to share in these discoveries with all of my mentees, every week. I just wanted to share some light from this particular light-bulb 💡
If you’ve heard Rachel speak ever (!) you probably know she’s on a mission to stop the late diagnosis of osteoporosis in patients and as part of this reminds us that this is a condition that develops over a lifetime not overnight – so waiting until women are 65yrs and men are 70yrs (which is the standard recommended age for BMD screening) seems a little remiss in terms of identifying our opportunity for preventative medicine. Are there earlier warning signs that we are ignoring or specific tests more sensitive and accessible than DXA scans that we could be ordering to better monitor patients who are at higher risk of bone demineralisation? The answers are of course, yes and yes! This Update in Under 30 outlines the clinical tools we should be using to uncover unhealthy bones earlier in our patients, how to implement them, their limitations and their strengths.