HISTON TABLETS

Indications

• Amenorrhea
• Irregular menstrual periods
• Dysmenorrhea
• Infertility
• Premenstrual syndrome
• Endometriosis

Dosage

Adults: The typical dosage for adults is 10 mg taken orally, three times a day, from day 5 to day 25

Mechanism of action

Dydrogesterone acts on progesterone receptors in the uterus, regulating the healthy growth and normal shedding of the womb lining. By doing so, it reduces the risk of endometrial hyperplasia and cancer in non-hysterectomised women. Its action helps create a complete secretory endometrium in an estrogen-primed uterus, without affecting ovulation or corpus luteum function.

Pharmacodynamics

As an orally active progestogen, dydrogesterone does not exhibit contraceptive effects at therapeutic levels, as it does not inhibit ovulation. It is characterized by its non-androgenic, non-estrogenic, and non-corticoid properties, making it distinct from other progestins. Dydrogesterone is effective in treating menstrual disorders, including absent, irregular, or painful menstrual periods, infertility, premenstrual syndrome, and endometriosis. Its unique profile supports its therapeutic use in conditions where progesterone is lacking or needs to be supplemented.

Pharmacokinetics

Dydrogesterone is well absorbed after oral administration, with peak plasma concentrations occurring within 1 to 3 hours. It has a half-life of approximately 5 to 7 hours, allowing for convenient dosing schedules. The drug is metabolized primarily in the liver and is excreted mainly via urine, with a minimal percentage eliminated unchanged. Its pharmacokinetic properties support its use as a safe and effective treatment option for various menstrual and reproductive health issues.

Contra-indications

• Known hypersensitivity to dydrogesterone or any excipients
• Active liver disease
• History of hormone-dependent malignancies, such as breast cancer
• Undiagnosed vaginal bleeding
• Thromboembolic disorders

Adverse effects

• Headache
• Nausea
• Breast tenderness
• Mood changes
• Weight gain
• Abdominal pain
• Dizziness
• Menstrual irregularities

Interactions

• Anticonvulsants may decrease the effectiveness of dydrogesterone
• Rifampicin may reduce plasma concentrations of dydrogesterone
• St. John's Wort may reduce the efficacy of dydrogesterone
• CYP3A4 inducers may affect dydrogesterone metabolism

Precautions

• Monitor for signs of thromboembolic events in patients with a history of such conditions
• Use with caution in patients with cardiovascular disease
• Consider the risk of endometrial hyperplasia in women with irregular menstruation
• Evaluate the benefits versus risks in patients with liver impairment

Pregnancy

Dydrogesterone is used during pregnancy to support the luteal phase and prevent miscarriage in women with progesterone deficiency. It should be prescribed cautiously and under medical supervision.

Breast-feeding

Dydrogesterone is considered safe during breastfeeding, but monitoring for any possible effects on the infant is advised.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Oral tablets

Mechanism of action

Dydrogesterone is a progestogen that works by regulating the healthy growth and normal shedding of the womb lining by acting on progesterone receptors in the uterus. Dydrogesterone is an orally-active progestagen. The addition of a progestagen greatly reduces the estrogen-induced risk of endometrial hyperplasia and cancer in non-hysterectomised women, by reducing the growth of the endometrium. Progestins cannot be equated as group with progesterone because some are inherently estrogenic, some slightly androgenic, and some purely progestational; correspondingly, their ovulation-inhibiting potentialities may be mediated in somewhat different ways. /Progestins/ The 17-hydroxy or acetoxy compounds, on the other hand, elicit responses more nearly resembling those of progesterone. They have little or no estrogenic or androgenic activity and may produce catabolic and slight diuretic effects. The 19-nor derivatives are more effective in postponing the normal menstrual period. /Progestins/ Accumulating evidence indicates that the neuropeptide substance P (SP) is predominantly involved in neurogenic inflammation and pain perception via its high-affinity neurokinin 1 receptor (NK-1R). Intriguingly, decreased pain sensitivity is found to be associated with high plasma progesterone levels. We hypothesize that progesterone may attenuate nociception and associated inflammatory response via NK-1R-dependent pathways. To address our hypothesis, we incubated splenic lymphocytes from CBA/J female mice with different concentrations of the progesterone derivative dydrogesterone. Subsequently, the expressions of NK-1R and T helper (Th1)-type cytokines were analyzed by flow cytometry. Next, we subcutaneously injected CBA/J mice with 1.25 mg of dydrogesterone in 200-microl sesame oil; control mice were sham-injected. Tail flick test to detect the nociceptive threshold was performed in 30-min intervals upon injection. Lymphocytes were isolated from blood and uterus and analyzed for NK-1R surface expression. Immunohistochemical analyses were performed to investigate the uterine tissue distribution of NK-1R. Dydrogesterone induced a decrease in the percentage of NK-1R+ lymphocytes in vitro and in vivo. Additionally, an increase in Th2-type and a decrease in Th1-type cytokines could be detected in vitro after incubation with dydrogesterone. An increased tail flick latency following dydrogesterone injection supported the concept that decreased expression of the NK-1R on lymphocytes is associated with an increased pain threshold. Taken together, these results clearly reveal a pathway by which dydrogesterone or progesterone respectively modulates the cross talk of the nervous, endocrine and immune systems in inflammation and pain. For more Mechanism of Action (Complete) data for DYDROGESTERONE (6 total), please visit the HSDB record page.

Pharmacodynamics

Dydrogesterone is an orally active progestogen which acts directly on the uterus, producing a complete secretory endometrium in an estrogen-primed uterus. At therapeutic levels, dydrogesterone has no contraceptive effect as it does not inhibit or interfere with ovulation or the corpus luteum. Furthermore, dydrogesterone is non-androgenic, non-estrogenic, non-corticoid, non-anabolic and is not excreted as pregnanediol. Dydrogesterone helps to regulate the healthy growth and normal shedding of the uterus lining. Therefore, it may be useful in the treatment of menstrual disorders such as absent, irregular or painful menstrual periods, infertility, premenstrual syndrome and endometriosis.