Lynestrenol

BRAND NAMES

Common brand names associated with lynestrenol include:

• Exluton (lynestrenol progestogen-only oral contraceptive; historically the most well-known brand) 

• Lynoral (combination product containing ethinylestradiol + lynestrenol; used in some markets for hormonal contraception)

MECHANISM OF ACTION

Lynestrenol is a prodrug synthetic progestogen that is converted in the liver to its active form, norethisterone. It works mainly by suppressing ovulation through inhibition of the hypothalamic–pituitary–ovarian axis, reducing LH and FSH secretion and preventing the LH surge. It also thickens cervical mucus to block sperm penetration and causes endometrial thinning, making implantation less likely.

PHARMACOKINETICS

Absorption

Lynestrenol is rapidly and well absorbed after oral administration and undergoes extensive first-pass metabolism in the liver. It is quickly converted to its active metabolite norethisterone, which is responsible for its pharmacological effects. Peak blood levels are typically reached within a few hours after ingestion.

Distribution 

Lynestrenol, after conversion to norethisterone, is widely distributed in the body and is highly bound to plasma proteins, mainly albumin and sex hormone–binding globulin (about 90–95%). It shows a relatively large volume of distribution, indicating good tissue penetration.

Metabolism

Lynestrenol is rapidly metabolized in the liver to its active form norethisterone. Norethisterone is further metabolized mainly by reduction and conjugation (glucuronidation and sulfation), producing inactive metabolites that are prepared for elimination.

Elimination

Lynestrenol (via its active form norethisterone) is eliminated mainly through the urine and feces after hepatic metabolism. Most of the dose is excreted as inactive glucuronide and sulfate conjugates. The elimination half-life of norethisterone is typically around 8–12 hours, allowing once-daily dosing in most contraceptive regimens.

PHARMACODYNAMICS

Lynestrenol is a progestogen that exerts its pharmacodynamic effects after conversion to norethisterone. It binds to progesterone receptors in target tissues, producing negative feedback on the hypothalamic–pituitary axis to suppress LH and FSH release and inhibit ovulation. It also thickens cervical mucus, making sperm penetration difficult, and induces endometrial atrophy, reducing the likelihood of implantation. These combined effects provide its contraceptive action.

ADMINISTRATION

Lynestrenol is administered orally, usually in tablet form, taken once daily at the same time each day to maintain consistent hormone levels. It is commonly used as a progestogen-only contraceptive or in combination with estrogen in some formulations, depending on the regimen.

DOSAGE AND STRENGTH

Lynestrenol is commonly available in oral tablet strengths of 0.5 mg, 1 mg, and 5 mg, depending on the formulation and indication. For contraception, it is typically given in a low daily dose (around 0.5–1 mg once daily) in progestogen-only regimens, while higher doses (e.g., 5 mg) have been used in some therapeutic indications such as menstrual disorders, though use varies by country and product.

DRUG INTERACTIONS

Lynestrenol may have clinically important interactions with drugs that induce hepatic enzymes, such as rifampicin, phenytoin, carbamazepine, and barbiturates, which can reduce its contraceptive effectiveness by increasing metabolism to inactive compounds. Some antiretroviral drugs and herbal products like St. John’s wort may also decrease its levels. Conversely, drugs that inhibit liver enzymes may increase progestin exposure and side effects.

FOOD INTERACTIONS

Lynestrenol has no significant clinically relevant food interactions. It can be taken with or without food, although taking it with food may help reduce mild gastrointestinal discomfort in some users. Food does not meaningfully affect its absorption or contraceptive efficacy.

CONTRAINDICATIONS

Lynestrenol is contraindicated in conditions such as known or suspected pregnancy, active or history of thromboembolic disorders, severe liver disease or liver tumors, and undiagnosed vaginal bleeding. It should also be avoided in patients with known hypersensitivity to the drug or its components, and in hormone-sensitive cancers such as breast cancer.

SIDE EFFECTS

• Irregular menstrual bleeding (spotting, breakthrough bleeding, amenorrhea)

• Headache

• Nausea

• Breast tenderness

• Mood changes

• Weight changes

• Acne

• Dizziness

• Changes in libido

OVER DOSE

Lynestrenol overdose is usually not serious and may cause nausea, vomiting, dizziness, and irregular bleeding. Treatment is supportive as there is no specific antidote.

TOXICITY

Lynestrenol has low acute toxicity, and serious poisoning is rare. Overdose mainly causes hormonal side effects like nausea, vomiting, dizziness, and abnormal bleeding. It is not usually life-threatening, and treatment is supportive.