Norethisterone
Norethisterone Uses, Dosage, Side Effects, Food Interaction and all others data.
Norethisterone has typical effects of a progestogen and converts the endometrium from the proliferative to the secretory phase. It may also have some oestrogenic, anabolic and androgenic activities, but these may not be significant. Norethisterone delays onset of periods and controls abnormal uterine bleeding. It also has contraceptive effects due to negative feedback inhibition of pituitary gonadotropin thus preventing ovulation.
Norethisterone is a synthetic oral progestin used for contraception or to treat other hormone-related conditions such as menopausal symptoms and endometriosis. As a synthetic progestin, norethisterone acts similarly to endogenous progesterone but with a much higher potency - it acts at the pelvic level to alter cervical and endometrial function, as well as via the inhibition of pituitary hormones that play a role in follicular maturation and ovulation. A small increase in the risk of developing breast cancer has been observed in patients using combined oral contraceptives, with some evidence also implicating progestin-only pills - patients starting hormonal contraception should be advised of this risk and should employ routine breast self-examinations to check for evidence of any developing masses.
| Trade Name | Norethisterone |
| Generic | Norethisterone |
| Norethisterone Other Names | 19-nor-ethindrone, 19-norethisterone, Norethindrone, Norethisteron, Noréthistérone, Norethisterone, Norethisteronum, Noretisterona |
| Type | |
| Formula | C20H26O2 |
| Weight | Average: 298.4192 Monoisotopic: 298.193280076 |
| Protein binding | Norethisterone is 38% bound to sex hormone-binding globulin and 61% bound to albumin. |
| Groups | Approved |
| Therapeutic Class | Drugs for menopausal symptoms: Hormone replacement therapy, Female Sex hormones, Oral Contraceptive preparations |
| Manufacturer | Wockhardt UK Ltd |
| Available Country | United Kingdom |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Norethisterone is used for:
- Dysfunctional uterine bleeding (DUB)
- Premenstrual syndrome (PMS), Mastopathy
- Timing of menstruation
- Endometriosis
- Menorrhagia
Norethisterone is also used to associated treatment for these conditions: Endometriosis related pain, Moderate to Severe Vasomotor Symptoms, Osteoporosis, Postmenopausal Osteoporosis, Vulvovaginal Atrophy, Hypoestrogenism, Moderate, severe, Vasomotor Symptoms caused by Menopause, Contraception, Hormone Replacement Therapy, Oral Contraceptives
How Norethisterone works
On a molecular level, progestins like norethisterone exert their effects on target cells via binding to progesterone receptors that result in downstream changes to target genes. Target cells are found in the reproductive tract, breast, pituitary, hypothalamus, skeletal tissue, and central nervous system. Contraceptive efficacy is derived mainly from changes to the cervical mucus, wherein norethisterone increases the cell content and viscosity of the mucous to impede sperm transport and migration. Norethisterone also induces a variety of changes to the endometrium - including atrophy, irregular secretion, and suppressed proliferation - that make it inhospitable for implantation. Working via a negative feedback loop, norethisterone also acts on both the hypothalamus and anterior pituitary to suppress the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. Suppression of these hormones prevents follicular development, ovulation, and corpus luteum development.
When used as a component of hormone replacement therapy in menopausal women, norethisterone’s value is mainly in suppressing the growth of the endometrium. As estrogen stimulates endometrial growth, the unopposed use of estrogen in postmenopausal women with an intact uterus can lead to endometrial hyperplasia which can increase the risk of endometrial cancer. The addition of a progestin to a hormone replacement therapy in this population protects against this endometrial hyperplasia and, therefore, lowers the risk associated with the use of hormone replacement therapies.
Norethisterone, along with other progestins and endogenous progesterone, has a low affinity for other steroid receptors, such as the androgen receptor and glucocorticoid receptor. While affinity and agonistic activity at these receptors is minimal, it is thought that androgen receptor agonism is responsible for some of the adverse effects observed with progestin use (e.g. acne, serum lipid changes).
Dosage
Norethisterone dosage
Breast cancer: 40 mg daily increasing to 60 mg daily if no regression is noted.
Contraception: 0.35 mg daily, or 0.5-1 mg daily when combined with oestrogen. As acetate: 0.6 mg daily, or 1-1.5 mg daily when combined with oestrogen.
Premenstrual syndrome: 5 mg tid on days 16-25 of cycle.
Progestogen component of menopausal hormonal replacement therapy: 0.7 mg as a continuous daily dose. As acetate: 1 mg daily for 10-12 days of a 28-day cycle.
Endometriosis: 10-25 mg daily continuously for 4-9 month. As acetate: 5-15 mg daily, start at 5 mg daily and increase by 2.5 mg at 14 day intervals. Take continuously for 4-9 month.
Menorrhagia: 10-15 mg daily in a cyclical regimen. Usual dose: 5 mg tid for 10 days as primary treatment, subsequently 5 mg bid on days 19-26 of cycle to prevent recurrence. As acetate: 2.5-10 mg daily in a cyclical regimen, beginning during the assumed latter half of the cycle.
Postponement of menstruation: 5 mg tid starting 3 days before expected onset of menstruation.
Side Effects
Mental depression, cholestatic jaundice, porphyria, epilepsy, migraine, headache, breast discomfort, dizziness, nausea and vomiting, changes in libido, appetite and weight, breakthrough bleeding, changes in menstrual flow, amenorrhoea, oedema, rash, melasma or cholasma, acne, urticaria, abnormal LFTs, moodswings, insomnia, thrombotic and thromoembolic events, optic neuritis, altered lipid profile.
Toxicity
The oral LD50 in mice 6 g/kg and the TDLo in human women is 42 mg/kg. There have been no reports of serious ill effects following overdose of oral contraceptives, including following ingestion by children. Symptoms of overdosage are likely to be consistent with the adverse effect profile of the contraceptive and may, therefore, include significant nausea and/or vomiting.
Precaution
Hypertension; CVS disease; hepatic impairment; epilepsy; lactation; new onset of migraine-type headache; asthma; renal impairment; history of clinical depression.
Interaction
Concentration may be reduced by CYP450 inducers (e.g. phenobarbital, phenytoin, carbamazepine, rifampicin, rifabutin, nevirapine, efavirenz, tetracyclines, ampicillin, oxacillin, co-trimoxazole) and ritonavir, nelfinavir (usually inhibitors of CYP450 but have inducing properties when used with steroid hormones). May cause additive fluid retention with NSAIDs, vasodilators. Adjustment in antidiabetic, thyroid hormone and anticoagulant therapy may be required.
Food Interaction
- Take with or without food. Co-administration with food slightly alters pharmacokinetics, but not to a clinically significant extent.
Volume of Distribution
The volume of distribution of norethisterone is approximately 4 L/kg. Sulfated metabolites of norethisterone, as well as small quantities of parent drug, have been shown to distribute into breast milk.
Elimination Route
The Cmax of norethisterone following oral administration of a single dose ranges from 5.39 to 7.36 ng/mL with a Tmax of 1-2 hours. AUC0-24 values following single oral doses range from approximately 30 to 37 ng*hr/mL. The oral bioavailability of norethisterone is approximately 64%. When applied transdermally, norethisterone is well-absorbed through the skin, reaches steady-state concentrations within 24 hours, and has a Cmax ranging from 617 to 1060 pg/mL at steady state.
Norethisterone is often formulated as norethisterone acetate, which is completely and rapidly deacetylated to norethisterone following oral administration - the disposition of norethisterone acetate is indistinguishable from that of orally administered norethisterone.
Half Life
The half-life of norethisterone has been variably estimated as 8-10 hours.
Clearance
The plasma clearance of norethisterone has been estimated as 0.4 L/hr/kg, and the intrinsic clearance is approximately 73-81 L/h.
Elimination Route
Following administration of radio-labeled norethisterone, slightly more than 50% of the administered dose was eliminated in the urine and 20-40% was eliminated in the feces.
Pregnancy & Breastfeeding use
Pregnancy Category X. Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.
Contraindication
Norethisterone should not be used in the presence of the conditions listed below, which are derived also from information on other progestogen-only products. Should any of the conditions appear during the use of Norethisterone, the use of the preparation must be discontinued immediately.
- Known or suspected pregnancy
- Lactation
- Thromboembolic processes
- Diabetes mellitus with vascular involvement
- Presence or history of severe hepatic disease as long as liver function values have returned to normal
- Presence or history of liver tumors (benign or malignant)
- Known or suspected sex-hormone dependent malignancies
- Hypersensitivity to the active substances or to any of the excipients
Acute Overdose
Acute toxicity studies performed with norethisterone acetate did not indicate a risk of acute adverse effects in case of inadvertent intake of a multiple of the daily therapeutic dose.
Storage Condition
Store in a cool and dry place, protected from light and moisture. Keep out of reach of children
Innovators Monograph
You find simplified version here Norethisterone
FAQ
What does Norethisterone do to the body?
Norethisterone (Norethisterone) is a synthetic and potent progestogen hormone which stops uterine bleeding. It also has some androgenic effects and some weak oestrogenic activity. Naturally occurring progestogens are the hormones that maintain the lining of the uterus.
Will Norethisterone stop my period?
Most women find that Norethisterone prevents their period from starting until they choose to stop taking the tablets. However, some women find that they have spotting or breakthrough bleeding while they are taking Norethisterone.
Do I get a period on Norethisterone?
Your periods may be irregular, or heavier/lighter than usual. You may also have vaginal bleeding (spotting) between periods. Do not stop taking your pills if this happens.
How does Norethisterone work as a contraceptive?
Norethisterone causes changes to the mucus of the cervix and the lining of the womb and affects the hormonal control system of the body, which may all contribute to the birth control (contraceptive) action. The effectiveness of the “progestogen-only” pill is lower than that of other birth control pills.
What happens when I stop Norethisterone?
Your periods are likely to stop during treatment and after you stop taking Norethisterone the patches of endometrial tissue may have shrunk.
How quickly does Norethisterone work?
You need to start taking the tablets 3 days before your period is due to start. Your period will usually start within 3 days of finishing the tablets. If you do not have a period after you finish a course of Norethisterone Tablets, check with your doctor in case you are pregnant.
Is Norethisterone safe?
Norethisterone is safe for most women to use on an occasional basis, but it is not recommended to use this to delay your period regularly. There are also some side effects associated with taking the medication.
Can Norethisterone cause weight gain?
Side effects including weight gain, hirsutism, acne, headache, nausea, and vomiting all did not appear to increase in incidence and no "disturbing side effects" were noted in any of the women.
What are the side effects of taking Norethisterone?
- Menstrual irregularities e.g. irregular bleeding, heavy menstruation, spotting between menstrual cycles, delayed or not having a menstrual cycle.
- Inform your doctor if.
- Stomach discomfort e.g. nausea, vomiting.
- Breast tenderness.
- Headache and dizziness.
How long will I bleed after taking Norethisterone?
Bleeding usually stops within 48 hours. Withdrawal bleeding resembling true menstruation occurs a few days after the end of treatment.
Can I get pregnant while taking Norethisterone?
If you delay your period by taking period delay medication, you will not be protected against pregnancy. If you have unprotected sex whilst taking norethisterone, you could become pregnant.
What happens if I miss a day of Norethisterone?
Every time you miss a dose or take a dose late your chance of pregnancy increases. When 1 pill is missed (even if only 3 hours late), take the missed pill as soon as possible and continue taking a pill each day at the regular time (use a back up method of birth control for the next 48 hours).
How long does it take for Norethisterone to stop period?
Vaginal bleeding of various amounts may occur between your regular menstrual periods during the first 3 months of use. This is sometimes called spotting when slight, or breakthrough bleeding when heavier. If this should occur, continue with your regular dosing schedule. The bleeding usually stops within 1 week.
How do I use Norethisterone to delay my period?
Doctor will advise you when to take Norethisterone and for how long. You'll usually be prescribed 3 Norethisterone tablets a day, starting 3 to 4 days before you expect your period to begin. Your period should arrive 2 to 3 days after you stop taking the medication.
Can I take Norethisterone on first day of period?
Norethisterone is given to take on days 5-26 of your menstrual cycle (day 1 is the first day of your period). Taking Norethisterone in this way does not act as a contraceptive.
How many days can I take Norethisterone?
Norethisterone should be taken for no longer than 20 days. you my take it for less if do not wish to delay your period for the 17 days. Once you stop taking Norethisterone your period should occur within 2 to 3 days and your cycles should continue as usual after this.
Is delaying your period bad?
It's fine to skip your "period" on the combined hormonal birth control pill. If you choose to skip your "period" continually, side effects can include breakthrough bleeding. Your uterus won't get “backed up” Make sure you know which kind of pill you have—monophasic or multiphasic—before skipping.
Does Norethisterone cause facial hair?
Side effects are Nausea, vomiting, headache, dizziness, mood swings, trouble sleeping, weight gain/loss, acne, breast swelling/tenderness, change in sexual interest, unwanted hair growth, or hair loss may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.
Can Norethisterone make you depressed?
Norethisterone can cause some side effects in some women, that include depressive symptoms, a rise in blood pressure, and migraine-type headaches.
What causes periods to delay?
Missed or late periods happen for many reasons other than pregnancy. Common causes can range from hormonal imbalances to serious medical conditions. There are also two times in a woman's life when it's totally normal for her period to be irregular: when it first begins, and when menopause starts.
How long should I take Norethisterone?
If you take Norethisterone for menstrual disorders or abnormal vaginal bleeding: You will most likely take the medicine for only 5 to 10 days. Vaginal bleeding will occur 3 to 7 days after your last dose. If you take Norethisterone for endometriosis: Norethisterone is usually taken daily long-term for several months.
