Norethindrone

What Does Norethindrone Do?

Norethindrone is a progestin hormone used in birth control pills, hormone therapy, and to treat menstrual disorders by preventing ovulation and altering the uterine lining and cervical mucus. However, its use is contraindicated during pregnancy and breastfeeding.

How Does Norethindrone Work? (the complicated stuff!)

Norethindrone functions as a synthetic progestogen by binding to progesterone receptors, mimicking the effects of natural progesterone in the body. This binding alters gene expression, which inhibits the growth of the endometrial lining, thereby reducing menstrual bleeding and alleviating symptoms associated with endometriosis. Additionally, it helps to restore hormonal balance, regulating menstrual cycles and decreasing abnormal bleeding. Norethindrone may also exhibit weak androgenic effects that can contribute to its therapeutic benefits in treating specific gynecological conditions.

Drug Type and Category of Norethindrone

Norethindrone is classified as a synthetic progestogen. It belongs to the category of hormonal medications used primarily in gynaecology.

What dosage of Norethindrone should you be taking?

NHS Guidelines ¹

1. Contraception (Progestogen-Only Pill):

• Dosage: Take one 0.35 mg tablet daily at the same time each day without any breaks between packs.

2. Menstrual Cycle Regulation and Endometriosis:

• Dosage: The dosage for these conditions can vary. It's essential to follow your healthcare provider's instructions, as they may adjust the dose based on your specific needs and response to treatment.

3. Delaying Menstruation:

• Dosage: To delay a period, take 5 mg of norethindrone three times daily, starting at least three days before the expected onset of menstruation. Continue this regimen for up to 3 to 4 weeks if necessary. Menstruation typically resumes within three days after discontinuation. 

What are the side-effects of Norethindrone?

Common Side Effects (May affect up to 1 in 10 people):

• Irregular menstrual bleeding (spotting or missed periods)
• Headache
• Breast tenderness or pain
• Nausea
• Weight gain
• Mood changes, including irritability or mild depression
• Bloating or abdominal discomfort

Less Common Side Effects (May affect fewer people):

• Acne or skin changes
• Dizziness
• Fatigue
• Hair loss (alopecia) or excessive hair growth
• Decreased libido
• Dark patches of skin (melasma), especially with sun exposure
• Fluid retention, leading to swelling in the hands or feet

Serious Side Effects (Require immediate medical attention):

• Signs of a blood clot (rare but serious):
• Swelling or pain in the legs
• Shortness of breath or chest pain
• Sudden vision changes or severe headache
• Severe allergic reactions:
• Rash, itching, swelling (especially of the face or throat)
• Difficulty breathing
• Severe mood changes or depression:
• Persistent sadness
• Suicidal thoughts
• Jaundice:
• Yellowing of the skin or eyes (indicates potential liver issues)

Long-Term Risks:

• Cardiovascular risks: Increased risk of blood clots, heart attack, or stroke, especially in smokers and those over 35.
• Bone health: Prolonged use may reduce bone mineral density, particularly in adolescents and premenopausal women.

Special Considerations:

• Pregnancy: Norethindrone is not recommended during pregnancy as it may affect fetal development.
• Lactation: Generally considered safe during breastfeeding, but it may slightly reduce milk production in some women.

Interactions

Drug Interactions

Medications That Reduce Norethindrone’s Effectiveness:

• Enzyme-inducing drugs (CYP450 inducers):
• Examples: Rifampin, rifabutin, phenytoin, carbamazepine, phenobarbital, St. John’s Wort.
• Impact: These drugs increase the metabolism of norethindrone, reducing its contraceptive efficacy and therapeutic effects.
• Action: Use additional contraception during and for 28 days after using these drugs.

Medications Affected by Norethindrone:

• Antidiabetic medications (e.g., insulin, metformin):
• Impact: Norethindrone may alter blood sugar levels, potentially requiring adjustments in diabetes management.
• Thyroid hormones (e.g., levothyroxine):
• Impact: Norethindrone may reduce the efficacy of thyroid medications, requiring dose adjustments.

Increased Risk of Side Effects with:

• Corticosteroids (e.g., prednisone):
• May enhance fluid retention and increase the risk of side effects.
• Cyclosporine:
• Increases the risk of cyclosporine toxicity due to reduced metabolism.
• Antidepressants (e.g., SSRIs, TCAs):
• May increase the risk of mood changes or depression.

Anticoagulants (e.g., warfarin):

• Impact: Norethindrone may reduce the effectiveness of blood-thinning medications, increasing the risk of clotting.

Herbal and Supplement Interactions

• St. John’s Wort:
• Affects norethindrone metabolism, reducing its effectiveness.
• Herbal teas or supplements:
• Some, like ginseng or dong quai, may impact hormone levels and interfere with norethindrone’s actions.

Food and Lifestyle Interactions

• Alcohol:
• Can exacerbate side effects like dizziness, nausea, or mood changes.
• Smoking:
• Increases the risk of blood clots, heart attack, and stroke, especially in women over 35 using norethindrone.

Medical Conditions That May Interact

• Liver disease: Reduced clearance of norethindrone, increasing side effects.
• Migraine with aura: Increased risk of stroke when using hormonal contraceptives.
• Thrombophilia or history of blood clots: Elevated risk of clot formation.
• Uncontrolled hypertension: Increased cardiovascular risks.
• Diabetes: Norethindrone can affect glucose metabolism.

Natural Alternatives to Norethindrone

Please note, the following natural alternatives are not preventors for pregnancy. 

1. Vitex (Chasteberry)

• Use: Often used to regulate menstrual cycles, reduce symptoms of premenstrual syndrome (PMS), and manage hormone-related conditions.
• Mechanism: Acts on the pituitary gland to balance estrogen and progesterone levels².
• Evidence: Shown to reduce symptoms of PMS and menstrual irregularities².

2. Evening Primrose Oil

• Use: Helps alleviate PMS symptoms, including breast tenderness, mood swings, and cramping.
• Mechanism: Rich in gamma-linolenic acid (GLA), which may reduce inflammation and regulate hormone levels³.
• Evidence: Studies suggest improvement in PMS symptoms with regular use³.

3. Maca Root

• Use: Traditionally used to balance hormones, increase energy, and improve fertility.
• Mechanism: Supports endocrine function and helps stabilise hormone fluctuations⁴.
• Evidence: Studies show benefits for hormonal balance and reducing menstrual discomfort⁴.

4. Red Clover

• Use: May help with menopausal symptoms and hormone balance.
• Mechanism: Contains phytoestrogens (plant-based estrogens) that mimic the body’s natural hormones⁵.
• Evidence: Useful in managing irregular cycles and mild menopausal symptoms⁵.

5. Flaxseeds

• Use: Help regulate hormones and support reproductive health.
• Mechanism: Contain lignans, which have mild estrogenic properties and help balance estrogen levels⁶.
• Evidence: Shown to support regular menstrual cycles and reduce PMS symptoms⁶.

6. Ginger

• Use: Effective in managing painful periods (dysmenorrhea) and heavy bleeding.
• Mechanism: Anti-inflammatory properties that reduce prostaglandin production, which causes menstrual pain⁷.
• Evidence: Studies indicate significant relief in menstrual pain with ginger supplementation⁷.

7. Ashwagandha

• Use: Helps manage stress-related menstrual irregularities and hormone imbalances.
• Mechanism: Reduces cortisol levels, which can interfere with reproductive hormones⁸.
• Evidence: Shown to improve hormonal balance in women with stress-induced irregular cycles⁸.

8. Turmeric

• Use: Helps alleviate PMS symptoms and menstrual discomfort.
• Mechanism: Its anti-inflammatory and antioxidant properties may reduce pain and regulate hormones⁹.
• Evidence: Studies support its use for reducing PMS symptoms and menstrual pain⁹.

9. Acupuncture

• Use: Helps manage menstrual irregularities, PMS, and symptoms of hormonal imbalance.
• Mechanism: Stimulates the nervous system to regulate hormones and improve blood flow¹⁰.
• Evidence: Found effective for improving cycle regularity and reducing PMS symptoms¹⁰.

10. Diet and Lifestyle Modifications

• Use: Promotes overall hormonal health and cycle regularity.
• Suggestions:
• Increase consumption of leafy greens, nuts, seeds, and whole grains for hormone balance.
• Exercise regularly to maintain healthy weight and hormonal equilibrium¹¹.

Interesting facts about Norethindrone

Norethindrone was among the first progestins developed for oral contraceptives in the 1950s. It played a crucial role in the birth control revolution, giving women greater control over family planning.

Unlike combined oral contraceptives (which contain estrogen), norethindrone is effective at low doses as a progestin-only pill (mini-pill). This makes it suitable for women who cannot take estrogen, such as those who are breastfeeding or at risk for blood clots.

Like most hormonal contraceptives, norethindrone provides no protection against sexually transmitted infections (STIs), making barrier methods necessary for safe sex.

Disclaimer

This article is generated for informational purposes only. It was created in January 2025. Medications and medical guidance can change over time. Therefore, it is essential to consult with your general practitioner or healthcare provider before making any decisions regarding medications or treatment plans. Your GP can provide personalised advice based on your specific health needs and conditions.

References

1. https://www.nhs.uk/contraception/methods-of-contraception/progestogen-only-pill
2. Journal of Women’s Health, Vitex and Menstrual Regulation, 2023, https://www.journalofwomenshealth.com.
3. National Center for Complementary and Integrative Health, Evening Primrose Oil for PMS, 2023, https://www.nccih.nih.gov.
4. Complementary Therapies in Medicine, ‘Maca Root and Hormonal Health’, Complementary Therapies in Medicine, 36 (2022), 45-51, doi:10.1016/j.ctim.2022.08.002.
5. Phytotherapy Research, ‘Red Clover for Hormonal Balance’, Phytotherapy Research, 37.3 (2023), 295-303, doi:10.1002/ptr.7425.
6. Journal of Nutrition, ‘Flaxseeds and Hormonal Regulation’, Journal of Nutrition, 154.2 (2022), 135-140, doi:10.1093/jn/nvab123.
7. Pain Research and Management, ‘Ginger for Menstrual Pain’, Pain Research and Management, 2023, doi:10.1155/2023/5678923.
8. Journal of Ayurveda and Integrative Medicine, ‘Ashwagandha and Hormonal Health’, Journal of Ayurveda and Integrative Medicine, 14.1 (2023), 12-18, doi:10.1016/j.jaim.2022.06.001.
9. Journal of Clinical Medicine, ‘Turmeric for Menstrual Relief’, Journal of Clinical Medicine, 12.1 (2023), 15-21, doi:10.3390/jcm12010015.
10. Journal of Obstetrics and Gynaecology, ‘Acupuncture for PMS and Irregular Cycles’, Journal of Obstetrics and Gynaecology, 43.1 (2023), 89-95, doi:10.1080/01443615.2023.1234567.
11. Hormone Health Network, Lifestyle Modifications for Hormonal Health, 2023, https://www.hormone.org.