Reviewed February 2020

Norethisterone: side effects, risks, and benefits

Norethisterone: side effects, risks, and benefits

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Using norethisterone for menorrhagia (heavy bleeding) | Should I take norethisterone? Women’s experiences | Is it possible to delay your period? Myths vs facts

You may have heard of norethisterone — a synthetic hormone commonly found in contraceptive pills— and wonder whether it is right for you. This article aims to give you some information that may help you make that decision.

What is norethisterone?

Norethisterone is a hormone belonging to a group called progestins, which are artificial forms of progesterone— a hormone that is found naturally within our bodies.

There are different preparations of norethisterone that can be used in different doses, which depend on what you are using it for.

Commonly, norethisterone it is used in the progestogen-only contraceptive pill, which is also known as the ‘mini-pill’. Norethisterone can also be used in combination with oestrogen in the combined oral contraceptive pill. When used in contraception, norethisterone works towards preventing pregnancy, controlling menstruation, helping to manage endometriosis pain, and managing premenstrual symptoms (PMS).

On its own, norethisterone 5mg tablets can be used taken to delay periods, which may be desirable if you are planning a holiday or have a sporting event coming up where you’d rather not have to worry about your period. It is important to remember that when taken as a 5mg tablet, norethisterone is not strong enough to act as a contraceptive, so you will need to use alternative forms of contraception.

How does norethisterone work?

Using norethisterone in contraception

When norethisterone is used in contraceptive pills, one way it works to prevent pregnancy is by suppressing a part of the brain called the pituitary gland where essential sex hormones — follicular stimulating hormone (FSH) and luteinising hormones (LH) — are released. These hormones are required for ovulation, so if they are not released, no egg is available to be fertilised. However, if you take the progesterone-only pill, FSH and LH are not always fully suppressed, and so ovulation can still sometimes happen. It is estimated that around 50% of women who take the mini pill still ovulate.1

Norethisterone may also be used to reduce period pain and to make periods lighter, and in some women, to help manage PMS

Another way that norethisterone works to prevent pregnancy is by thickening the cervical mucus, which makes it difficult for sperm to swim into the womb to be fertilised. The thickened mucus also slows down the movement of the egg as it travels down the Fallopian tubes.

Finally, progestins work to thin the womb lining, making it difficult for the fertilised egg to implant successfully.

Norethisterone for period delay

Period delay is a common reason for using norethisterone, particularly if you’re going on holiday and would rather not experience your monthly bleed while away. It is generally safe to use norethisterone for this purpose, however, be sure to seek advice from your doctor as there are some instances where using norethisterone isn’t advisable.

Norethisterone works to delay periods by keeping the levels of progesterone high. Since the lining of the womb sheds once progesterone levels fall, keeping these levels high can result in lighter or delayed periods.

Other effects of norethisterone on periods

Norethisterone may also be used to reduce period pain and to make periods lighter, and in some women, to help manage PMS.

It is thought that norethisterone helps manage period pain because it thins the lining of the womb but also stabilises it and prevents it from shedding, which has been shown to help with endometrial pain.2 In addition, period pain is worse during ovulation, therefore by preventing ovulation from occurring it follows that norethisterone can lessen period pain. Norethisterone causes the womb lining to be thinner so menstrual bleeding is less heavy, although this effect is variable in different women.

It is uncertain why the pill is useful in alleviating PMS symptoms, but it may be that a steady stream of hormones delivered by the pill can reduce emotional symptoms. Although we don’t know for sure what causes PMS, it has been suggested that it is due the rapid changes in hormone levels (oestrogen and progesterone). Therefore, having a steadier level of progesterone may work to prevent PMS. This does not happen in all women and we not know why.

Who can use norethisterone?

Norethisterone is suitable for most women, however there are some instances in which it wouldn’t be safe to take. For example, it is not advised to take norethisterone if you might be pregnant, however no adverse effects have been shown for either mother or baby when women have conceived while using the mini pill.

Women who are in the active stages of breast cancer (generally within first 5 years of diagnosis) are not advised to use norethisterone due to concerns that it might make the cancer worse, unless progestogens are being used as part of their treatment.3 It is also not advised for women who have a history of breast cancer, however norethisterone can be used if there is no evidence of disease after five years and if using non-hormonal contraceptives is not an option.

If you have undiagnosed abnormal periods, it is best that your doctor first investigates the cause of your irregular bleeding before advising on whether norethisterone is a possible course of action

If you have, or you think you may have breast cancer, you doctor will be able to advise on whether norethisterone is suitable for you.

Women with benign or malignant liver tumours, severe cirrhosis, or acute liver disease should avoid norethisterone because the liver will not be able to handle these hormones.

If you have undiagnosed abnormal periods, it is best that your doctor first investigates the cause of your irregular bleeding before advising on whether norethisterone is a possible course of action. This is because irregular bleeding may be due to many causes, and it is best to make sure it is nothing that could contraindicate with norethisterone.

Women who are taking other medications such as drugs used for epilepsy should consult a healthcare professional before starting the progesterone-only pill, as there are some medications that it could interact with.

What are the benefits of norethisterone?

The mini pill can be useful for women who cannot take contraception that contains oestrogen, such as the combined pill. This includes women who:

  • Have a very high risk of blood clots, with multiple risk factors for heart disease such as smoking, being in an older age group, diabetes, and high blood pressure
  • Women with known history of stroke or heart disease, current breast cancer, or migraine with sensory symptoms

Taking oestrogen could make these medical conditions worse or increase the risk of them.

Norethisterone carries a lower risk of blood clots compared with oestrogen, but there is some evidence that the overall risk of blood clots is increased for women using norethisterone versus the general public who are not using norethisterone.4 You should always speak to your doctor to understand any risks particular to you before taking norethisterone.

Another advantage of the mini pill is that once stopped, fertility returns quickly, which is good news if you have come off contraception because you want to get pregnant. Norethisterone is useful for treating other conditions, such as dysmenorrhea (painful periods), abnormal menstrual bleeding, and pain associated with endometriosis (when bits of womb tissue grow elsewhere in the body, other than in the womb).

Side effects of norethisterone

As with all medications, taking norethisterone can be associated with side effects. When taken as contraception, one of the most common side effects is irregular periods, which is a common reason for stopping. Irregular bleeding can vary from stopping completely5 to prolonged bleeding, breakthrough bleeding, or spotting in one or more cycles in up to 70% of women.6 The reason for the irregular bleeding is not completely understood, but early breakdown (atrophy) of the womb lining plays a role.7

Progesterone-only pills containing norethisterone should be taken every day and ideally at the same time each day. This is because the hormone does not last long in the blood stream

The mini pill can cause breast tenderness in some women, which may be due to extra stimulation of the hormones in the breast tissue. Studies have also shown that women who use the mini-pill develop more cysts in their ovaries compared with women who are not taking the pill. In general, these do not lead to any problems unless it causes pain, and if this is the case, then it may be worthwhile to change to a different contraception. It is uncertain why these cysts develop, but it is thought that as the low dose of progesterone in the mini pill doesn’t work to stop the cysts from forming, more cysts are then able to form.8

There have been reports of some women having worse acne flares when they are on the mini pill. This may be related to progesterone stimulating the sweat glands and increasing sebum secretion, therefore causing acne.9 It is not known which women experience certain side effects more than others.

There is no scientific evidence that mini pills will make women gain weight,10 it is uncertain whether it affects depression,11 and it has not been found to increase in frequency of headaches,12 but these symptoms have been reported.

Norethisterone has not been associated with serious complications. Overall, using norethisterone in the mini pill reduces the risk of ectopic pregnancies (pregnancies outside of the womb) because it prevents pregnancy overall. But if pregnancy does occur, then the likelihood of pregnancy being ectopic is higher than if the woman is not taking any contraception.13 At the moment, there is no evidence that using norethisterone in the mini pill increases breast cancer risk.14 The mini pill also does not prevent from sexually transmitted diseases, so it is worth using a condom for this additional protection.

How should I take norethisterone?

Progesterone-only pills containing norethisterone should be taken every day and ideally at the same time each day. This is because the hormone does not last long in the blood stream. It needs to be taken daily to stop any hormone-free days. If you miss the pill by more than 3 hours, it is advised that extra contraception such as use of condom is used in the meantime for the next 2 days whilst the routine is re-started.

If norethisterone 5mg tablets are used period delay, then it should be taken three times a day, and you should start taking it three days before the expected start of your period. When norethisterone is stopped, periods will occur generally 2-3 days after.

It is important to remember that there are different preparations of norethisterone and the dose used may be different, so norethisterone used to delay periods or used to prevent bleeding may not have an effective contraceptive effect. If you actively do not want to be pregnant whilst taking norethisterone, then it is important to use additional alternative forms of contraception.

Featured image is of a handful of scattered white pills, against a gradient purple-to-pink background

Last updated February 2020
Next update due 2022

Dr. Diana Chiu, MBChB (Hons) MRCP PGCERT (Med Ed) PhD

Diana received her medical degree, with honours, from the University of Manchester. She then went on to receive basic and specialist medical training within the north west of England. She carried out in-depth research in medicine and was awarded a PhD in 2016. Currently, she is finishing her medical training at a large teaching hospital, and one of her greatest interests is medical education. She is an advanced life support instructor and writes regularly for post-graduate examination websites, and also holds a PGCERT in medical education with distinction.

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References

  1. Milsom, I., and Korver, T., Ovulation incidence with oral contraceptives: a literature review, Journal of Family Planning and Reproductive Health Care, October 2008, vol 34, issue 4, pp 237-246
  2. Zito, G., et al., Medical treatments for endometriosis-associated pelvic pain, Biomed Res Int, August 2014, article ID: 191967 [online] https://doi.org/10.1155/2014/191967 (accessed 5 February 2020)
  3. BNF, ‘Norethisterone’, National Institute for Health and Care Excellence (NICE), 2020, [online], https://bnf.nice.org.uk/drug/norethisterone.html#cautions (accessed 5 February 2020)
  4. Ibid
  5. Maybin, J.A., and Critchley, H.O.D., Medical management of heavy menstrual bleeding, Women’s Health, January 2015, vol 12, issue 1, pp 27-34
  6. FSRH, Progestogen-only pills, Clinical Guidance, Clinical Effectiveness Unit, Faculty for Sexual and Reproductive Health, March 2015 (amended April 2019), [online], https://www.fsrh.org/standards-and-guidance/documents/cec-ceu-guidance-pop-mar-2015/ (accessed 5 February 2020)
  7. Fraser, I.S., A survey of different approaches to management of menstrual disturbances in women using injectable contraceptives, Contraception, October 1983, vol 28, issue 4, pp 385-397
  8. Speroff L, Darney PD. A Clinical Guide For Contraception, 5th ed, Lippincott Williams & Wilkins, Philadelphia 2011, p 105
  9. Ebede, T.L., et al. Hormonal Treatment of Acne in Women, The Journal of Clinical and Aesthetic Dermatology, December 2009, vol 2, issue 12, pp 16-22
  10. Lopez, L.M., Progestin-only contraceptives: effects on weight, Cochrane Database Systematic Reviews, August 2016, vol 28, no. 8, article number CD008815
  11. Worly, B.L., et al., The relationship between progestin hormonal contraception and depression: a systemic review, Contraception, June 2018, vol 97, issue 6, pp 478-489
  12. FSRH, Progestogen-only pills, Clinical Guidance, Clinical Effectiveness Unit, Faculty for Sexual and Reproductive Health, March 2015 (amended April 2019), [online], https://www.fsrh.org/standards-and-guidance/documents/cec-ceu-guidance-pop-mar-2015/ (accessed 5 February 2020)
  13. Furlong, L.A., Ectopic pregnancy risk when contraception fails. A review,Journal of Reproductive Medicine, November 2002, vol 47, issue 11, pp 881-885
  14. FSRH, Progestogen-only pills, Clinical Guidance, Clinical Effectiveness Unit, Faculty for Sexual and Reproductive Health, March 2015 (amended April 2019), [online], https://www.fsrh.org/standards-and-guidance/documents/cec-ceu-guidance-pop-mar-2015/ (accessed 5 February 2020)