HRT: Developments in therapy

Abstract

Various forms of oestrogen have been available for use as Hormone Replacement Therapy (HRT) for approximately 50 years. However, there has been little change in the mode of administration until the last 10-15 years. Although the oral route has remained the mainstay of therapy, non-oral routes of administration have been developed. During the 1970s it became clear that use of unopposed oestrogens in women with an intact uterus resulted in an increase in risk of endometrial carcinoma and thus the current practice of adding a sequential progestogen each month, to prevent endometrial hyperplasia, was introduced. However, certain progestogens can cause side-effects and some of the metabolic changes which they induce are potentially undesirable. Thus the search continues for new oral progestogens which are more 'metabolically friendly' than those in current use. Additionally, non-oral delivery systems for progestogens have been studied, such as the transdermal route (patches) and local administration within the uterine cavity (progestogen-containing intra-uterine devices). Both these strategies may minimise their symptomatic, psychological and metabolic effects. Continuous (every day) administration of progestogens in combination with the oestrogen, or the use of new compounds (e.g. tibolone) may overcome the problem of regular withdrawal bleeding which some women find unacceptable. However, it remains to be determined whether such therapies are as efficacious as conventional oestrogen/sequential progesterone regimens.

Utilisation of hormone replacement therapy in the United Kingdom

“…Our results show that these are becoming increasingly favoured by physicians in the UK, over those containing CEEs, which are structurally less similar to the oestrogens produced by the human ovary. 27 Our study also demonstrates the differences between the UK and the US in the progestogens prescribed in combined HRT. In our study, only 4.3% of the prescriptions for combined HRT preparations contained MPA as the progestogen while in the US, MPA is by far the most frequently prescribed progestogen in combined HRT.…”

“…Oestradiol is an endogenous female oestrogen, which is currently a component of several HRT preparations. Our results show that these are becoming increasingly favoured by physicians in the UK, over those containing CEEs, which are structurally less similar to the oestrogens produced by the human ovary 27 . Our study also demonstrates the differences between the UK and the US in the progestogens prescribed in combined HRT.…”

Estradiol and progesterone bioavailability for moderate to severe vasomotor symptom treatment and endometrial protection with the continuous-combined regimen of TX-001HR (oral estradiol and progesterone capsules)

“…TX-001HR is the first oral formulation that combines bioidentical E2 and P4 in a single softgel capsule being evaluated for the treatment of moderate to severe VMS in postmenopausal women with a uterus. Combining both E2 and P4 in a single capsule may facilitate compliance and convenience to the patient, 30 but may also increase efficacy and safety while reducing the incidence of withdrawal bleeding. 15,31,32 Additionally, various studies have suggested that bioidentical P4 may have a better side effect profile than synthetic progestogens regarding breast cancer 33,34 and venous thromboembolism.…”

The Clinical Biochemistry of the Menopause and Hormone Replacement Therapy

“…There are limited data on its long-term effects. 77 Use of the OCP until the menopause: In the UK the upper age limit for prescription of the combined OCP is 45 years. In America, an expert committee have advised the Food and Drugs Administration (FDA) to remove this upper age limit for healthy, non smoking women."…”