Effect of progestogens on cardiovascular health in women with POF (01)

• Research type

  Research Study

• Full title

  A randomised controlled trial to compare the effect of micronized progesterone and Medroxyprogesterone Acetate on the vascular elasticity, lipid profile and coagulation cascade of women with premature ovarian failure.

• IRAS ID

  103936

• Contact name

  Haitham Hamoda

• Eudract number

  2012-004511-30

• ISRCTN Number

  n.a

• Research summary

  Background: POF is characterised by primary or secondary amenorrhoea, hypoestrogenism and elevated gonadotrophin levels occurring in women under 45. It can have devastating short and long-term effects secondary to sex steroid deficiency, namely, climacteric symptoms, subfertility, osteoporosis and cardiovascular disease. Despite the first case being described in 1942, the optimal treatment is unknown. The aim is to provide physiological hormonal levels, and thus, help minimise the adverse effects. Currently, hormone replacement therapy (HRT) and the combined oral contraceptive pill (COCP) are the most commonly used but, the most effective dose or type is unknown. Studies have looked at the benefits of oestrogen; however, little research has been carried out on the effect of the type of progesterone used on various parameters. Few women are prescribed oestrogen-only, the majority have a combination of oestrogen and progesterone. Research has suggested that progesterone is responsible for some of the adverse effects seen, including coronary heart disease. Despite this, progesterone is essential in women with an intact uterus to reduce the risk of endometrial cancer. It is important to acknowledge that these trials recruited older post-menopausal women and may have used non-physiological preparations, thus, the data may not be correctly extrapolated to include this cohort. Subsequent reports have shown a reduction in the incidence of heart disease with HRT if commenced early, suggesting a role in the prevention of primary disease. Rosano et al. have shown that different combinations can have varied effects on the vascular system and that the type of progestin used is of paramount importance. There are many classes of progestogens, each with different pharmacological properties, and thus, different side effect profiles. In contrast however, oral micronized progesterone is not thought to negatively impact on the oestrogenic benefits on lipoprotein profiles. Furthermore, mode of administration may impact on their vascular properties. Oestrogen patches lead to lower peak plasma concentrations with a more sustained release resembling physiological levels, in contrast to oral preparations. In addition, hormonal therapy has been shown to increase the relative risk of venous thromboembolic (VTE) disease by 2- to 4-fold. Progestogen- and oestrogen-only hormonal contraceptives are thought to have less risk compared to those containing a combination of the two. The Oestrogen and Thromboembolism Risk study group, reported that oral but not transdermal oestrogen is associated with an increased risk of VTE in postmenopausal women. Micronized progesterone has been shown to have a neutral effect on the vasculature and therefore, not to increase the VTE risk compared with non-users. Aim: Randomised controlled un-blinded 2-arm trial comparing the effects of micronized progesterone (Utrogestan©) and MPA, used in combination with transdermal oestradiol patches (Evorel©) on the cardiovascular system, lipid profile and coagulation cascade of women with POF (90 recruits). Objectives: Primary: To assess the effect of micronized progesterone and MPA on vascular elasticity. This will be assessed by examining the changes in pulse wave analysis in women with POF receiving combined oestrogen/progestogen HRT. Secondary: To assess the effect of micronized progesterone and MPA on: 1. Pulse wave velocity. 2. Lipid profiles. 3. Coagulation cascade. 4. Side-effect profile and women??s satisfaction with their HRT regimen.

• REC name

  London - West London & GTAC Research Ethics Committee

• REC reference

  12/LO/1957

• Date of REC Opinion

  16 Jan 2013

• REC opinion

  Further Information Favourable Opinion