Progestogens suppress endometrial proliferation and produce secretory endometrium in the second half of the menstrual cycle if there has been prior oestrogenic stimulation. Accepted medical indications for progestogen use are as a component of the Pill or Hormone Replacement Therapy; in the management of endometriosis; for the treatment of dysfunctional uterine bleeding, and to prevent or treat endometrial hyperplasia. Different types of progestogens are prescribed according to the type of complaint. Other factors may need to be taken into account, such as the androgenic capacity of a particular progestogen.
Cyproterone acetate is a progestogenic anti-androgen and is used when acne and excess hair growth are considerations. It can be used with oestrogen in the Pill (Diane, Brenda) as a contraceptive, and is also available for menopausal women in some types of Hormone Replacement Therapy preparations (Climen) to prevent hirsutism. Dydrogesterone, hydroxyprogesterone and medroxyprogesterone (Provera) are progestogens that have few androgenic effects and also have less effect on lipids than the more androgenic progestogens. This makes them suitable for contraceptive purposes, especially where there is evidence of increased risk of thromboembolic events (such as among smokers), and for women using Hormone Replacement Therapy post-menopause. The progestogens with the most pronounced androgenic effects are levonorgestrel, norgestrel and norethisterone.
The third-generation progestogens, gestodene, desogestrel and etonorgestrel, are included in some combined oral contraceptives. These progestogens have less androgenic activity and are less likely to cause acne, weight gain and hirsutism. Gestodene and desogestrel have approximately double the tendency to cause venous thromboembolism than levonorgestrel, perhaps because they are often prescribed to older women. They are rarely used as the first choice of oral contraceptive for this reason.
Progestogens can cause symptoms of nausea, bloating, acne, breast tenderness, weight gain and mood changes which may be related to the androgenising (male hormone) effects of the drugs.
Progestogens are commonly prescribed for heavy periods and dysfunctional uterine bleeding, even though many women who have these problems do not have irregularities in progesterone production. The progestogens cause complete shedding of the endometrium when the medication is stopped. This often corrects the abnormal bleeding.
These drugs need to be given for about 21 days — usually from day five to day 25 of the menstrual cycle. They are usually prescribed for between one and three menstrual cycles, but sometimes longer administration is needed. The androgen-like side-effects and blood lipid abnormalities associated with Primolut N and the norethisterones restrict their use to no more than 6-12 months.
An alternative treatment for menorrhagia is the levonorgestrel-releasing IUD (Mirena). This type of direct delivery of a progestogen causes the endometrium to shrink after about three months’ use, and many women report very light periods, spotting or amenorrhoea. The IUD is also a contraceptive device and is sometimes suggested as the progestogen component of Hormone Replacement Therapy when women have difficulties with oral progestogens.
Provera can be used to treat premenstrual breast pain. It is usually prescribed between day five to 25 to modulate the effects of oestrogen on breast tissue and to suppress pituitary-ovarian function. Although up to 80 per cent of women improve on Provera, many experience an initial worsening of their symptoms and up to 40 per cent will relapse after stopping the drug.
Provera and Duphaston (dydrogesterone) are the common progestogens used for endometriosis. These preparations can be given in the last part of the cycle, but are ususally given continuously to create a pregnancy-like state with no period. About 30 per cent of women are troubled by spotting and breakthrough bleeding until the drug starts to work or the dose is adjusted. These drugs are relatively inexpensive (compared to some of the others used for endometriosis) and can give significant pain relief without serious long-term side effects.
On the downside, Duphaston can cause unpleasant side-effects including increased hirsutism, mood changes and a deeper voice. Fertility is not improved after using either of the progestogens. The return to a regular cycle may be delayed for many months and endometriosis may return after progestogen therapy.
Progestogens are necessary for menopausal women taking oestrogens who have not had a hysterectomy. They are given continuously at a low dose to cause endomentrial thinning, or intermittently at higher doses to induce endometrial shedding. Provera (medroxyprogesterone acetate) 10 mg is commonly used and is prescribed for ten to twelve days each month. Alternatively, lower doses of between 2.5-5 mg are given continually to shrink the endometrium and protect it from the over-stimulatory effects of oestrogen.
When side-effects from progestogens are a problem, the B vitamins, herbal diuretics or evening primrose oil can sometimes reduce symptoms. Some women using progestogen as a component of Hormone Replacement Therapy stop the drug if they develop symptoms, or alternatively use wild yam creams as a substitute. This is an extremely risky practice and will substantially increase the risk of oestrogen-induced endometrial cancer. Wild yam cream is not progesterogenic and will not protect the endometrium against these adverse effects. These women would be advised to either stop the Hormone Replacement Therapy entirely or to speak to their doctor about a suitable alternative.