Dydrogesterone - Pharmacology

Pharmacology

When administered orally Dydrogesterone has advantageous pharmacological properties compared to endogenous progesterone:

• It is orally active at low dosages.
• It has selective progestogenic properties without any traditional hormonal activity.
• The amount absorbed is more predictable than for progesterone, since it is not broken down as easily when passing through the digestive system.

Dydrogesterone is characterised by progestational and antiestrogenic activity. This is demonstrated by its ability to induce a secretory transformation in the endometrium of immature or ovariectomised animals after they have been primed with estrogens (cf. the Clauberg test). The oral progestogenic potency of dydrogesterone is 20 times higher than that of progesterone.

The progestational efficacy and potency of dydrogesterone was confirmed by standard test (i.e. delay of menses and induction of withdrawal bleeding). The benefits of estrogen or other target organs are not compromised by dydrogesterone.

Unlike other synthetic progestogens, dydrogesterone is not chemically related to testosterone. Its low affinity for the androgen receptor explains why it has no unwanted androgenic effects even at high doses and after prolonged treatment:

• no virilisation (acne, voice changes, hirsutism) of the adult female
• no virilising effects on the genital tract of the female foetus
• no effect on the fertility of the offspring.

Dydrogesterone is not converted into estrogen, and has no adverse estrogenic effects on fertility or sexual development.

At recommended doses, dydrogesterone has no effect on ovulation in healthy women:

• the biphasic pattern of the basal body temperature is maintained
• normal ovulatory rise in estrogen and pregnanediol
• normal premenstrual biopsy
• no modification of vaginal cytology
• cytological evidence of ovulation
• the formation of the corpus luteum has been confirmed by laparotomy

These beneficial results are of particular relevance to the use of dydrogesterone in women who wish to become pregnant.

Dydrogesterone is free from adverse effects on carbohydrate metabolism. It does not cause changes in body weight, blood pressure, glucose tolerance or blood lipid ratios. No significant effects on blood coagulation or liver function tests have been reported. These favourable results are crucial in long-term therapy, e.g. postmenopausal HRT.