Progestogens

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oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Progesterone is the naturally occurring progestogen and a subclass of the sex hormones. It is secreted by the ovary as part of the menstrual cycle. It was first isolated in 1934 by Butenandt. Progestogens are synthetic forms of progesterone.

Progestogens were developed because progesterone could not be absorbed orally, although a novel method of processing progesterone via micro-ionising is available.[1]

They provide an alternative form of hormonal contraception for patients deemed unsuitable for the combined oral contraceptive pill (COCP). This makes it suitable for the following patients:

  • Heavy smokers
  • Women with hypertension
  • Women with diabetes mellitus
  • Past history of deep vein thrombosis
  • Migraine

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There are two main groups of progestogen:

  • Progesterone and its analogues: dydrogesterone and medroxyprogesterone.
  • Testosterone analogues: norethisterone and norgestrel. Desogestrel, norgestimate and gestodene are derivatives of norgestrel.

Progesterone and its analogues are less androgenic than the testosterone analogues. Dienogest is a hybrid progestogen.[2] 

Division according to generation

Based on time since market introduction:

  • First generation: norethindrone, norgestrel and medroxyprogesterone.
  • Second generation: levonorgestrel (active component of norgestrel).
  • Third generation: desogestrel.[3]
  • Tablets.
  • Depot:
    • Requires full counselling and warning regarding menstrual disturbances and delay in return to full fertility. Use beyond two years of Depo-Provera® needs to be evaluated carefully. Depo-Provera® provides contraception for twelve weeks.
    • Noristerat® provides contraception for eight weeks, which may be useful in certain scenarios.
  • Implants - Nexplanon® provides contraception for up to three years when implanted subdermally.
  • Levonorgestrel-releasing intrauterine system.
  • Vaginal gel, suppositories and injections of progesterone may be used for a variety of indications, including infertilitydysfunctional uterine bleeding and recurrent miscarriage.

Progestogens should be avoided in patients with a history of liver tumours, those with genital or breast cancer (unless being used to treat these conditions), severe arterial disease, undiagnosed vaginal bleeding and acute porphyria, or if there is a history of idiopathic jaundice, severe pruritus or pemphigoid gestationis occurring during pregnancy.

Menstrual disorders

Regulation of abnormal bleeding or induction of menstruation.[2][3]

  • Progestogens lead to withdrawal bleeding in oligomenorrhoea and secondary amenorrhoea states.
  • Medroxyprogesterone acetate is the most widely used.
  • Progestogens are also used in dysfunctional uterine bleeding, with or without oestrogens.
  • It is necessary to ensure that the patient does not have atypical endometrial hyperplasia prior to treating dysfunctional uterine bleeding (this applies more to older patients).
  • Using progestogens does not treat the underlying cause of the menstrual disorder.
  • Progestogens have been widely used for menorrhagia but are ineffective compared with tranexamic acid or mefenamic acid.
  • Progesterones can be used to delay menses: norethisterone can be taken three days before the expected start date and continued. Normal menstruation will occur 2-3 days after stopping.

Contraception

Either alone for oral contraception, in the levonorgestrel-releasing intrauterine system (see below), long-acting contraception injections as in Depo-Provera® or Noristerat®, or the progestogen implant Nexplanon®, or in combination with oestrogens in the COCP. Also used for emergency contraception.

  • The progestogen component leads to anovulation which is enhanced by oestrogens.
  • Progestogens also lead to thickened cervical mucus which is hostile to sperm.
  • Prolonged progestogen exposure leads to an atrophic endometrium which reduces the chance of implantation of a fertilised ovum.
  • The progestogen-only contraceptive pill is useful for postpartum contraception, as it does not interfere with breast-feeding.

Intrauterine systems

  • Progesterone or progestogen can be delivered directly into the uterus, using a coil. See the separate article Intrauterine System.

Hormone replacement therapy (HRT)

See also the separate article on Hormone Replacement Therapy.

  • Postmenopausal women who have a uterus and take oestrogens for HRT require progestogen, either on a cyclical or a continuous basis, to prevent cystic hyperplasia of the endometrium and the possible development of endometrial cancer.
  • Postmenopausal women have unopposed oestrogens which can lead to endometrial hyperplasia and carcinoma. Use of progestogens for twelve or more days in each cycle can reduce this risk.
  • Continuous progestogens have been used to prevent unwanted uterine bleeding. This usually needs to be combined with oestrogens to prevent endometrial atrophy.

Endometriosis

See also the separate article on Endometriosis. A commonly used progestogen in endometriosis is medroxyprogesterone acetate.[2]

  • Progestogens are thought to prevent implantation and growth of regurgitated endometrium.
  • Some theories suggest that progestogens have an anti-inflammatory effect on ectopic endometrium.
  • Progestogens have been shown in several studies to reduce pain from endometriosis, with minimal side-effects.
  • Progestogens have no effect on fertility rates in endometriosis.
  • Progestogens have been previously used in the prevention of recurrent miscarriages - this is no longer recommended.

Acne[5]

Progestogens such as dienogest are also anti-androgenic.

  • They block androgen receptors and 5-alpha reductase which converts testosterone to the more potent dihydrotestosterone.
  • This also occurs in the sebaceous glands of the skin, leading to reduction in seborrhoea and improvement in acne.
  • They can also reduce hirsutism.

Premenstrual syndrome

No definite evidence to support the role of progestogens in the premenstrual syndrome.[6]

  • The premenstrual syndrome consists of mental and physical symptoms which are related to the menstrual cycle.
  • The aetiology is unclear.
  • Some theories suggest it is related to sex steroids, as it is not seen in anovulatory cycles.
  • It is thought to relate more to oestrogens.
  • Some investigators theorised that a lack of progestogens is the cause, leading to the use of progestogens in this condition.
  • There is no clear evidence to support the use of progestogens.

Anticancer hormonal therapy

Treatment is not curative but can induce remission in 15-30% of patients.[7]

Palliative role in neoplastic disease

Progestogens stimulate appetite and weight gain, especially in breast neoplasm (longer duration compared with corticosteroids). Effect can be enhanced with concomitant use of NSAIDs - eg, ibuprofen.[8]

  • Women's age - using depot progesterones as contraception after the age of 40 may contribute to bone density loss.
  • Previous breast cancer.[9]
    • There is a small increase in the risk of breast cancer in women who are on or have recently used the progestogen-only contraceptive pill.
    • However, the progestogen-only contraceptive pill can be used in women with a previous history of breast cancer if there has been no evidence of recurrence for five years and non-hormonal contraceptive methods are unacceptable.[4]
  • Examine: breasts, blood pressure.
  • Investigations: HDL in high cardiovascular risk group.
  • Educate the patient to self-examine breasts.
  • Urticaria, acne, weight gain
  • Fluid retention
  • Hypertension
  • Nausea, constipation
  • HDL cholesterol can be suppressed - this is seen more with first- and second-generation progestogens.
  • Hypertension.
  • Decreased glucose tolerance.
  • Depressed mood.
  • Cardiovascular disease - risk is higher with older forms of COCP and greater in females with concomitant risk factors.
  • Hirsutism (rare).
  • Jaundice (rare - thus, contra-indicated in hepatic impairment).

Further reading & references

  1. Apgar BS, Greenberg G; Using progestins in clinical practice. Am Fam Physician. 2000 Oct 15;62(8):1839-46, 1849-50.
  2. Vercellini P, Fedele L, Pietropaolo G, et al; Progestogens for endometriosis: forward to the past. Hum Reprod Update. 2003 Jul-Aug;9(4):387-96.
  3. Fraser IS, Kovacs GT; The efficacy of non-contraceptive uses for hormonal contraceptives. Med J Aust. 2003 Jun 16;178(12):621-3.
  4. British National Formulary
  5. Raudrant D, Rabe T; Progestogens with antiandrogenic properties. Drugs. 2003;63(5):463-92.
  6. Backstrom T, Andreen L, Birzniece V, et al; The role of hormones and hormonal treatments in premenstrual syndrome. CNS Drugs. 2003;17(5):325-42.
  7. Pascual Lopez A, Roque i Figuls M, Urrutia Cuchi G, et al; Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. J Pain Symptom Manage. 2004 Apr;27(4):360-9.
  8. Yavuzsen T, Davis MP, Walsh D, et al; Systematic review of the treatment of cancer-associated anorexia and weight loss. J Clin Oncol. 2005 Nov 20;23(33):8500-11.
  9. Colditz GA; Estrogen, estrogen plus progestin therapy, and risk of breast cancer. Clin Cancer Res. 2005 Jan 15;11(2 Pt 2):909s-17s.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Gurvinder Rull
Current Version:
Peer Reviewer:
Prof Cathy Jackson
Document ID:
400 (v4)
Last Checked:
06/09/2013
Next Review:
05/09/2018