Dr John C Stevenson, MB BS, FRCP, FESC

Abstract | CV

Abstract

Progestins – are they all the same?

John C Stevenson
Endocrinology & Metabolic Medicine, Faculty of Medicine, Imperial College London, London UK

Progestins are added to oestrogen in hormone replacement therapy (HRT) for endometrial protection. However, they have different potencies, different side-effect profiles and different metabolic effects, depending on the type of progestin. In general terms, progestins are classified according to whether they are derivatives of testosterone or progesterone. Classically, the 19 nor-testosterone derivatives such as levo-norgestrel and norethisterone acetate, are regarded as being androgenic, yet certain C-21 steroids, such as medroxyprogesterone acetate, may also have androgenic activity. It is now realised that, within the broad groups, progestins may differ considerably; they have differing affinities for various steroid receptors, including oestrogen, androgen and glucocorticoid receptors, and also varying agonist and antagonist effects.

The side-effect profile of progestins varies according to their androgenic or progestogenic properties, but there is considerable overlap of these side-effects between individuals. Of more importance, the metabolic effects of various progestins may differ quite substantially, with important consequences for certain disease risks. Metabolic effects mainly impact on cardiovascular disease risk, and thus the choice of progestin in HRT regimens may be quite crucial in this respect. Although recent randomised clinical trials have suggested that there is no beneficial effect of HRT with respect to coronary heart disease (CHD), this is probably due to inappropriate doses of the hormones used, rather than to the types of hormones. Nevertheless, there is clearly potential benefit to be obtained for CHD risk when considering the choice of hormones, oestrogens and progestins, if appropriate does are used. This makes the different metabolic effects between progestins very important when considering CHD benefits and risks.

Oestrogen lowers cholesterol, by lowering levels of LDL. They also increase levels of HDL, and overall this is a beneficial effect. These effects vary according to the type of oestrogen used and their route of administration. Reductions in LDL cholesterol are achieved with all forms of HRT. Oral oestrogen increases HDL cholesterol more than transdermal oestradiol. The addition of an androgenic progestogen, such as norgestrel, prevents this increase, whilst non-androgenic progestogens such as dydrogesterone have little impact. Oral oestrogens result in increases in triglycerides, whilst transdermal oestradiol decreases them. The addition of androgenic progestogens decreases triglycerides, whilst the non-androgenic do not prevent an increase. 

Oestrogens also affect glucose and insulin metabolism. Insulin resistance is a pivotal metabolic disturbance underlying CHD development. Oestradiol increases pancreatic insulin secretion, insulin sensitivity and insulin elimination. Androgenic progestogens may oppose these effects but non-androgenic progestogens do not.

We now have an increasing number of progestins that can be used in HRT, and also in oral contraceptives. The metabolic effects of these progestins need to be considered, particularly in terms of their impact on cardiovascular risk.

CV

Dr John Stevenson is a Reader in Endocrinology and Metabolic Medicine, Faculty of Medicine, Imperial College, London. He is an Honorary Consultant Physician at the Royal Brompton Hospital where he jointly runs the UK’s first Female Heart Disease Clinic, and at St Mary’s Hospital, London. He has over 300 publications in journals and books.

Dr Stevenson is currently Chairman of the charity Women’s Health Concern, Executive Committee Member of the European Menopause and Andropause Society and of the British Menopause Society, Fellow of the European Society of Cardiology, and Member of the Scientific Advisory Board of the National Osteoporosis Society (UK). He is a past Chairman of the British Menopause Society, past Treasurer of the UK Bone and Tooth Society, and past Executive Committee Member of the International Menopause Society.