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Increasing experience with hypermobile patients suggests that, in females, hormonal aspects are important. Adult and pubescent females who present with a history of dislocations should be encouraged to keep a diary in order to see whether the dislocations are linked to their menstrual cycle, or to their choice of contraception.



In pubescent females, if joints, previously hypermobile, only become symptomatic at the time of the onset of their periods, this would suggest a hormonal influence, though growth spurts that might have occurred about the same time could also be contributing. A further clue would be if the symptoms from hypermobile joints become particularly severe in the few days just prior to menstruation in a normal, regular female cycle unaltered by contraceptives. Another clue might be that symptoms suddenly deteriorate or dislocations become more frequently on the introduction of one of the progesterone based contraceptives. Clinical experience suggests that the progesterone-like compound called Drospirenone, which is a component of a preparation marketed as Yasmin, is particularly problematic in hypermobile patients. (Prof. Howard Bird MA MD FRCP)

 

Better understanding the potential for hormonal influence in hypermobile patients may offer the opportunity for a different style of management. For example, if the diary shows that dislocations happen, or increase, around the time of the patient’s monthly period you may suggest that they  brace the affected joints during those most vulnerable days as a preventative measure. Alternatively, the patient may wish to discuss with their GP the option of trialing a combined contraceptive with the highest dose of oestrogen they can tolerate without side effects, just to see if this improves symptoms. If symptoms do improve, then in discussion with their GP, the patient might be willing to accept possible side effects for a better quality of life.

 

 

 

Hormonal Aspects of Hypermobility: Prof. Howard Bird - University of Leeds, UK

 

'Some female patients with hypermobility have been disappointed when symptoms of which they are complaining to their doctor, nurse or friends are summarily, even chauvinistically, dismissed as ‘hormonal’.  There is actually a considerable amount of truth in this though only occasionally will the person making this diagnosis have thought through all the ramifications. This article considers what types of hypermobility might be susceptible, what hormones might aggravate the symptoms and, when this is occurring, how things might be improved.​'

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Hormones involved.

Hormone is sometimes described as a ‘chemical messenger’ that is secreted from a gland circulates through the bloodstream and, finally, reaches the organ at which it is directed where it exerts its effect.

Although there are many types of hormones, all of different structures, two main groups are relevant to hypermobility.
 

Firstly are the corticosteroids, which comprise three families.  The first group, the mineralo-corticoids, alter minerals and fluids within the body and probably have no influence on hypermobility.  The second group, sometimes referred to as metabolic steroids, are secreted from the adrenal gland and control the diurnal (or 24-hourly) variation in body function, which allows organs to rest during sleep but ‘tones them up’ during the day.  This, in turn, may produce cyclical symptoms of pain and stiffness over a 24-hour period in joints but this is normally only a minor problem.  The third group comprises the sex hormones, which are divided into three types, androgens (mainly in males) and oestrogens and progestogens (mainly in females).  The balance between oestrogens and progestogens, which is constantly changing, controls the 28-day menstrual cycle in the female in whom these hormones are almost absent prior to puberty and tail off after the menopause.

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A further group of hormones relevant to hypermobility have a specific function in pregnancy.  Relaxin is considered to relax the ligaments just prior to childbirth so the pelvis can open widely to allow the safe passage of the foetal head.  Prolactin produces milk when the mother is breastfeeding and also has a relaxing effect on the joints.  In addition, during pregnancy, oestrogens and progestogens climb in concentration, all of which accounts for the undoubted loosening of the joints in pregnancy.  This normally remits soon after childbirth but may be prolonged if the mother is breastfeeding.  Some research that we did several years ago suggested that this invariably made joints looser in a first pregnancy, made them slightly looser in a second pregnancy but gave no further additional loosening in third or subsequent pregnancies.

​What types of hypermobility are affected?


In males, in whom hypermobility is often less pronounced than in females of the same age, cortisol may contribute to diurnal variation in symptoms as in females but hormones related to pregnancy, clearly, are not produced.  The predominant sex hormones in males are androgens, which probably have very little effect on collagen though may increase muscle bulk around the joints.  In general this is likely to be helpful, the increased muscle power more than outweighing any effect on the collagen structure.

In females, it is quite a different story.  Although oestrogen tends to stabilise collagen, progestogens loosen it.  Many hypermobile patients, though not all, noticed a worsening in symptoms, more pain in the joints, clumsiness or a greater tendency to dislocate in the five days leading up to menstruation and in the few days after menstruation.  This is exactly the time when the progesterone compounds far exceed the stabilising oestrogen compounds.  This effect is most pronounced when the joint hypermobility is due mainly to collagen structure (the clue here is that all joints are almost equally lax throughout the body).  Where the hypermobility is a marker of unusually shaped bony surfaces at the joint (typically these individuals have very pronounced hypermobility at only a small number of joints), the effect of hormones is much less pronounced.

Those females whose joints become worse at the time of menstruation often note that if the periods become irregular, for whatever reason, joints not only become worse but are worse for longer.  This may be because in these patients progesterone is present in high concentrations at times when it would not normally be present.

Sometimes irregularity of periods suggests gynaecological conditions such as a cyst on the ovary or a condition called endometriosis.  In a few patients we have suspected this diagnosis on the basis of joint deterioration alone, even before symptoms have become severe enough to attract the attention of a gynaecologist!

​Problems with contraceptives


A variety of hormonal contraceptives are available.  Many are ‘combined’ contraceptives, either a mixture of oestrogen or a progestogen given at the same time or contain these two drugs sequentially, the progestogen after the oestrogen to mimic the normal female menstrual cycle. Others are entirely progestogen containing.  Injected contraceptives (the most common is called Provera) are entirely progesterone and recently intra-uterine devices that are impregnated with a reservoir of progesterone (e.g. the Mirena coil) have become popular.

When careful gynaecological and rheumatological histories are taken together, it is surprising how frequently hypermobility, which was only slightly worse at the time of normal unmodified menstruation, becomes significantly worse with certain contraceptive pills, especially those containing progesterone alone or with progesterone depo contraception preparations or with mechanical devices impregnated with progesterone.

If you have hypermobile joints and have been taking hormones to modify menstruation or as contraceptives, you should discuss this further with your doctor, perhaps showing him/her this article, since doctors tend to be well versed in other side effects resulting from hormones, though not necessarily with the effect these have on your ligaments.  Oestrogens, like progestogens, have their own side effects, one of the principal ones being a slight tendency to cause venous thrombosis, a feature much less frequently seen with progestogens.  Therefore a progestogen-only preparation may have been prescribed for good and well-intentioned reasons, even though the downside is it will have made the joints worse.  In general, however, patients with hypermobility are safer avoiding injectable progesterone and progesterone impregnated devices.  They might also be better avoiding contraceptive pills that contain progesterone derivatives alone.  However, if such a preparation was introduced deliberately in a patient for whom high oestrogen levels would be dangerous, it may be worth trying a different progesterone contraceptive.  Newer progestogens (such as Desogestrel) are derivatives of nor-ethisterone, which is more closely related to testosterone than the early progesterone analogues such as didrogesterone and medroxyprogesterone.  There does seem to be individual variation in response within this group so it may be worth trying one or two such hormones in turn.

The hormonal content of all contraceptives is clearly listed in the British National Formulary, allowing general practitioners a wide and informed choice.

If there are increased joint symptoms associated with menstrual irregularities in a patient not taking a contraceptive pill, it may also be worth trying an oestrogen-only preparation for a trial period in the first instance to see if this improves things.  If it does, the choice of whether any slight risk in using such a preparation is worth taking for the significant improvement in the joints might ultimately be a decision for the patient though should be taken in conjunction with the General practitioner, if necessary with expert gynaecological advice.

Similar arguments apply to hormone replacement therapy after the menopause.  This normally involves a small amount of oestrogen to which a progestogen is added in women with an intact uterus.  Since the oestrogen amount is very small (deliberately so in view of the slight increased risk of breast cancer when oestrogens are given to the elderly as well as the risk of thrombosis), the amount of oestrogen is often not enough to provide a protective effect for the joints.

(Prof. Howard Bird - amended March 2008)

 

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