FEMOSTON 1/10 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

Indications

• Menopausal symptoms
• Hormone replacement therapy
• Osteoporosis prevention

Mechanism of action

Oestradiol functions by binding to estrogen receptors, specifically estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), as well as the G Protein-coupled estrogen receptor (GPER). Upon binding, the receptor-ligand complex translocates to the nucleus, where it regulates gene transcription and the formation of messenger RNA. This process leads to the synthesis of specific proteins that mediate the effects of estradiol, including relief from vasomotor symptoms and urogenital atrophy, as well as beneficial impacts on bone density and lipid profiles.

Pharmacodynamics

Oestradiol alleviates vasomotor symptoms such as hot flashes and urogenital symptoms like vaginal dryness and dyspareunia. It positively influences bone density by inhibiting bone resorption, and it can enhance the plasma lipid profile. Additionally, estradiol stimulates hepatic synthesis of proteins like sex hormone-binding globulin (SHBG) and thyroid-binding globulin (TBG), while also suppressing follicle-stimulating hormone (FSH) production in the anterior pituitary gland. However, oestradiol can induce a hyper-coagulable state, increasing the risk of cardiovascular events, deep vein thrombosis (DVT), and stroke, especially in high-risk patients.

Pharmacokinetics

Oestradiol is rapidly absorbed after oral administration, with peak plasma concentrations reached within a few hours. It undergoes extensive first-pass metabolism in the liver, leading to a shorter half-life. Oestradiol is primarily metabolized via the cytochrome P450 enzyme system. It is excreted primarily in the urine as conjugated metabolites. The pharmacokinetics may vary based on the route of administration and the formulation used.

Contra-indications

• Known hypersensitivity to estradiol or any excipients in the formulation
• Current or history of thromboembolic disorders
• Severe liver disease
• Estrogen-dependent tumors
• Undiagnosed abnormal genital bleeding
• Pregnancy

Adverse effects

• Nausea
• Vomiting
• Headache
• Breast tenderness
• Mood changes
• Weight gain
• Vaginal bleeding
• Increased risk of thromboembolic events
• Hypertension

Interactions

• CYP450 enzyme inducers (e.g., rifampicin, carbamazepine) may decrease estradiol levels
• Anticonvulsants may affect estrogen metabolism
• Certain antibiotics may alter the efficacy of estrogen therapy
• Other hormone therapies may interact with estradiol

Precautions

• Monitor patients for signs of thromboembolic events
• Caution in patients with a history of hormone-dependent cancers
• Regular monitoring of blood pressure is recommended
• Consideration of risks in patients with cardiovascular disease

Pregnancy

Estradiol should not be used during pregnancy due to potential harm to the fetus.

Breast-feeding

Estradiol may pass into breast milk; caution is advised when administered to nursing mothers.

Storage

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

Formulations

• Tablets
• Transdermal patches
• Injectable forms
• Topical gels

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.

Mechanism of action

Estrogen is found in the the breast, uterine, ovarian, skin, prostate, bone, fat, and brain tissues. The main source of estrogen in adult women during the reproductive period of life is the ovarian follicle, which secretes 70 to 500 mcg of estradiol each day. After menopause, however, the majority of endogenous estrogen is produced by transformation of androstenedione (which is secreted by the adrenal cortex) to estrone in the peripheral tissues. Both estrone and its sulphate conjugated form, estrone sulphate, represent the most abundant estrogens found in postmenopausal women. Estradiol, however, is considerably more potent than estrone and estriol at the estrogen receptor (ER). As a result, the higher estrone concentration in postmenopausal population, can cause various undesirable effects. These effects may include hot flashes, chills, vaginal dryness, mood swings, irregular menstruation, and chills, in addition to sleep problems. Estradiol workings by binding to subtypes of the estrogen receptor: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). It also exerts potent agonism of G Protein-coupled estrogen receptor (GPER), which is recognized an important regulator of this drug's rapid effects. Once the estrogen receptor has bound to its ligand, it enters the nucleus of the target cell, regulating gene transcription and formation of of messenger RNA. This mRNA makes contact with ribosomes producing specific proteins that express the effect of estradiol upon the target cell. Agonism of estrogen receptors increases pro-estrogenic effects, leading to the relief of vasomotor and urogenital symptoms of a postmenopausal or low estradiol state. Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol at the receptor level. ... After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women. Estrogens have an important role in the reproductive, skeletal, cardiovascular, and central nervous systems in women, and act principally by regulating gene expression. Biologic response is initiated when estrogen binds to a ligand-binding domain of the estrogen receptor resulting in a conformational change that leads to gene transcription through specific estrogen response elements (ERE) of target gene promoters; subsequent activation or repression of the target gene is mediated through 2 distinct transactivation domains (ie, AF-1 and AF-2) of the receptor. The estrogen receptor also mediates gene transcription using different response elements (ie, AP-1) and other signal pathways. Recent advances in the molecular pharmacology of estrogen and estrogen receptors have resulted in the development of selective estrogen receptor modulators (eg, clomiphene, raloxifene, tamoxifen, toremifene), agents that bind and activate the estrogen receptor but that exhibit tissue-specific effects distinct from estrogen. Tissue-specific estrogen-agonist or -antagonist activity of these drugs appears to be related to structural differences in their estrogen receptor

Pharmacodynamics

Estradiol acts on the on the estrogen receptors to relieve vasomotor systems (such as hot flashes) and urogenital symptoms (such as vaginal dryness and dyspareunia). Estradiol has also been shown to exert favorable effects on bone density by inhibiting bone resorption. Estrogen appears to inhibit bone resorption and may have beneficial effects on the plasma lipid profile. Estrogens cause an increase in hepatic synthesis of various proteins, which include sex hormone binding globulin (SHBG), and thyroid-binding globulin (TBG). Estrogens are known to suppress the formation of follicle-stimulating hormone (FSH) in the anterior pituitary gland. **A note on hyper-coagulable state, cardiovascular health, and blood pressure** Estradiol may cause an increased risk of cardiovascular disease, DVT, and stroke, and its use should be avoided in patients at high risk of these conditions. Estrogen induces a hyper-coagulable state, which is also associated with both estrogen-containing oral contraceptive (OC) use and pregnancy. Although estrogen causes an increase in levels of plasma renin and angiotensin. Estrogen-induced increases in angiotensin, causing sodium retention, which is likely to be the mechanism causing hypertension after oral contraceptive treatment.