Hormones and Hypermobility Professor Howard Bird considers what types of hypermobility might be susceptible, what hormones might aggravate the symptoms and, how symptoms might be managed. Which hormones are involved? A 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 mineralo-corticoids, that alter minerals and fluids within the body and probably have no influence on hypermobility those sometimes referred to as metabolic steroids (for example, cortisol), that 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. 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. The predominant sex hormones in males are androgens, and in particular testosterone. A further group of hormones relevant to hypermobility have a specific function in pregnancy. Relaxin relaxes the ligaments just prior to childbirth so the pelvis can open widely to allow the safe passage of the foetal head. However, although it is observed that joint laxity can increase in pregnancy, studies have not demonstrated a clear relationship between the level of relaxin and the degree of laxity. Other factors must be involved. During pregnancy, oestrogens and progestogens climb in concentration; this might also account for loosening of the joints in pregnancy. This normally remits soon after childbirth but may be prolonged if the mother is breastfeeding. What effect can hormones have on hypermobility? In both males and females the 24-hour changes in metabolic steroids may produce cyclical symptoms of pain and stiffness over a 24-hour period in joints but this is normally only a minor problem. In males the predominant androgen hormones 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. This requires assessment by a gynaecologist. Problems with Contraceptives A variety of hormonal contraceptives is available. Many are ‘combined’ contraceptives, either a mixture of oestrogen or a progestogen given at the same time or they contain these two drugs sequentially, the progestogen after the oestrogen to mimic the normal female menstrual cycle. Others contain entirely progestogen. Injected contraceptives are entirely progesterone and recently intra-uterine devices that are impregnated with a reservoir of progesterone (so-called ‘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 (intra muscular injection) 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; they will be well versed in other side effects resulting from hormones, but 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 (blood clots), 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. If such a preparation were introduced deliberately in a patient for whom high oestrogen levels would be dangerous, it might 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. Hormone replacement therapy Similar arguments to those above for contraception 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. Professor Howard Bird MA, MD, FRCP Emeritus Professor of Pharmacological Rheumatology, University of Leeds Updated August 2017. Version 3. Reviewed by Dr A Hakim. Planned Date of Review August 2020. For the medical references this article uses, please contact us using this form.