Dydrogesterone

Uses and Administration

Dydrogesterone is a progestogen structurally related to progesterone ( Refer to ). It does not have oestrogenic or androgenic properties.

Dydrogesterone has been given orally in the treatment of menstrual disorders such as menorrhagia ( Refer to ), usually in a dose of 10 mg twice daily in a cyclical regimen, and for the treatment of endometriosis ( Refer to ) in a dose of 10 mg two or three times daily cyclically or continuously. It has also been given cyclically in doses of 10 mg once or twice daily, or continuously in doses of 5 mg daily, for endometrial protection during menopausal HRT ( Refer to ).

In threatened miscarriage suggested doses have been 40 mg initially followed by 10 mg or more every 8 hours, continued for a week after symptoms cease then gradually reduced unless symptoms return. In recurrent miscarriage suggested doses have been 10 mg twice daily given cyclically until conception then continuously until week 20 of pregnancy, the dose may then be gradually reduced. However, such use is not recommended unless there is proven progesterone deficiency. Cyclical dydrogesterone has also been used in infertility ( Refer to ) in doses of 10 mg twice daily.

(last reviewed 2010-06-30; last modified 2008-06-25)

Adverse Effects, Treatment and Precautions

Adverse Effects and Precautions

As for progestogens in general (see Progesterone, Refer to and Refer to ). See also under Hormone Replacement Therapy, Refer to and Refer to .

(last reviewed 2010-06-30; last modified 2008-06-20)

Porphyria

The Drug Database for Acute Porphyria, compiled by the Norwegian Porphyria Centre (NAPOS) and the Porphyria Centre Sweden, classifies dydrogesterone as porphyrinogenic; it should be prescribed only for compelling reasons and precautions should be taken in all patients.1

(last reviewed 2010-06-30; last modified 2011-11-15)

References

1. The Drug Database for Acute Porphyria. Available at: Link (accessed 04/10/11)

Pregnancy

Anomalies (non-virilising) of the genito-urinary tract were found in a 4-month-old baby whose mother had taken dydrogesterone 20 mg daily from the eighth to twentieth week of pregnancy and 10 mg daily from then until term.1 She had also been given hydroxyprogesterone caproate 250 mg by intramuscular injection weekly from the eighth to the twentieth week.

(last reviewed 2010-06-30; last modified 2008-06-20)

References

1. Roberts IF, West RJ. Teratogenesis and maternal progesterone.Lancet. 1977; ii: 982. PubMed

Interactions

As for progestogens in general (see Progesterone, Refer to ).

(last reviewed 2010-06-30; last modified 1998-10-23)

Therapeutic Use

• Sex Hormones and their Modulators

Last Updated 1/21/20

Interactions of Progesterone

Interactions

Enzyme-inducing drugs such as carbamazepine, phenobarbital, phenytoin, and rifampicin may enhance the clearance of progesterone and the progestogens. These interactions are likely to reduce the efficacy of progestogen-only contraceptives (see Refer to ), and additional or alternative contraceptive measures are recommended.

Aminoglutethimide markedly reduces the plasma concentrations of medroxyprogesterone acetate and megestrol, possibly through a hepatic enzyme-inducing effect; an increase in progestogen dose is likely to be required.

Since progesterone and other progestogens can influence diabetic control an adjustment in antidiabetic dosage could be required. Progestogens may inhibit ciclosporin metabolism leading to increased plasma-ciclosporin concentrations and a risk of toxicity (see Refer to ).

(last reviewed 2015-04-14; last modified 2011-05-04)

Pharmacokinetics

Progesterone has a short elimination half-life and undergoes extensive first-pass hepatic metabolism when given orally; oral bioavailability is very low although it may be increased somewhat by an oily vehicle and by micronisation. Progesterone is absorbed when given buccally, rectally, or vaginally, and rapidly absorbed from the site of an oily intramuscular injection.

Various derivatives have been produced to extend the duration of action and to improve oral activity. Esters of progesterone derivatives such as hydroxyprogesterone caproate are used intramuscularly, and megestrol acetate is orally active. The ester medroxyprogesterone acetate is used orally and parenterally. 19-Nortestosterone progestogens have good oral activity because the 17-ethinyl substituent slows hepatic metabolism.

Progesterone and the progestogens are highly protein bound; progesterone is bound to albumin and corticosteroid binding globulin; esters such as medroxyprogesterone acetate are mainly bound to albumin; and 19-nortestosterone analogues are bound to sex-steroid binding globulin and albumin. Progesterone is metabolised in the liver to various metabolites including pregnanediol , which are excreted in the urine as sulfate and glucuronide conjugates. Similarly, progestogens undergo hepatic metabolism to various conjugates, which are excreted in the urine. Progesterone is distributed into breast milk.

(last reviewed 2015-04-14; last modified 2010-06-04)

Reviews.

(last reviewed 2015-04-14; last modified 2008-06-20)

References

1. Kuhl H. Comparative pharmacology of newer progestogens.Drugs. 1996; 51: 188–215. PubMed

2. Stanczyk FZ. Structure-function relationships, metabolism, pharmacokinetics and potency of progestins.Drugs Today. 1996; 32 1–14.

3. Schindler AE, et al.. Classification and pharmacology of progestins.Maturitas. 2003; 46 7–S16. PubMed