Tibolone is an analogue of the progestin, norethynodrel. After ingestion it is converted to three metabolites, namely 3-alpha- and 3-beta-hydroxytibolone, which have oestrogenic effects, and delta-4-isomerase, which has progestogenic and androgenic properties. Both the oestrogenic metabolites bind to the alpha-oestrogen receptor but not the beta-oestrogen receptor, while the delta-4 isomer binds to the alpha- and beta-oestrogen, progestogen and androgen receptors.
Tibolone is also a sulphatase inhibitor, blocking conversion of oestrone sulphate to oestrone, as well as stimulating local sulphotransferase activity. In contrast to other forms of postmenopausal hormonal therapy, it decreases sex hormone binding globulin and so increases circulating free testosterone, thereby further adding to its androgenicity. Tibolone significantly decreases vasomotor symptoms, mood disorders, insomnia, bone loss and vaginal atrophy. It has a favourable impact on the cardiovascular system and minimal impact on the endometrium and on mammary tissue. It has been classified as a selective tissue oestrogenic activity regulator.
Tibolone has a favourable impact on the ‘feeling of wellbeing’. This may be attributed to the increase of betaendorphin levels in the pituitary gland and plasma that occurs with its use, the androgenic impact of the delta-4- isomer metabolite on the brain, or the greater availability of testosterone because of lowered sex hormone binding globulin. All these specific features not only have a positive effect on mood, including fatigue and malaise, but have a beneficial effect on sexual wellbeing, including sexual desire, frequency of orgasm, sexual responsiveness, arousability and fantasies. It also improves vaginal pulse amplitude (a measure of vaginal blood flow) in postmenopausal women, normalises the vaginal maturation index, increases vaginal lubrication, and generally decreases the symptoms of vaginal atrophy.
In women who have a history of increased breast density, tibolone should be the drug of choice to start postmenopausal hormone therapy.
There was consensus that tibolone is an important treatment option in the management of the menopause. In addition, there are specific groups of postmenopausal women who will benefit significantly from use of tibolone after the menopause – postmenopausal women with:
- Vasomotor symptoms or significant mood swings, or who are taking psychoactive medication at the time of the menopause
- Those with poor sexual function, whether due to poor libido and/or dyspareunia
- Those in premature menopause because of a bilateral salpingo-oophorectomy at a young age, including women who have had surgery for endometriosis
- Those with a history of breast tenderness or increased mammographic density, or who were on other conventional hormonal therapy when their increased mammographic density was noted and who wish to continue with hormonal therapy
- Those with spontaneous premature ovarian failure
- Those with an increased risk for fracture or who have had a fracture because of osteoporosis, and are in the age group 50-60 years
- Pre-, peri- and postmenopausal women on gonadotrophin-releasing hormone analogues who require ‘add-back therapy’.
Source: Guidozzi F, et al. Guideline for the use of tibolone in South Africa. SAJOG 2011;17;2:31-35.