Obstetrics and Gynaecology chapters
Hormonal treatment of menstrual disorders
The drug treatments for heavy bleeding, painful periods, premenstrual syndrome, polycystic ovary syndrome and endometriosis: what each agent does, how much it helps, and where it sits in the treatment ladder.
- For heavy menstrual bleeding the first-line hormonal choice is the levonorgestrel intrauterine system, which cuts blood loss by about 95% at one year.
- Non-hormonal options are tranexamic acid (loss down by about 50%) and mefenamic acid (down by about 25%, and it eases pain).
- GnRH analogues switch the ovaries off but cause a low-oestrogen state, so they are short-term and usually need add-back hormone replacement.
On this page
Overview
Menstrual disorders are among the commonest reasons women attend a clinic. Treatment is usually medical first, surgical later, and the choice turns on two questions: does she want to keep her fertility, and is there a structural cause such as fibroids, polyps or adenomyosis? Hormonal treatment works mainly by thinning the endometrium, by stopping ovulation and cyclical hormone swings, or by switching the ovaries off altogether.
Heavy menstrual bleeding
Counselling before any treatment should cover all the options with their benefits and risks, the wish for future fertility, whether structural disease is present, associated pain or pressure symptoms, other illnesses, contraindications to drugs, suitability for surgery and previous uterine surgery.
Medical treatment, in the recommended order
| Treatment | Mechanism | Effect |
|---|---|---|
| Levonorgestrel intrauterine system (52 mg) | Local progestogen; marked endometrial atrophy | Blood loss down about 95% at 1 year; 7 or 8 of 10 users become amenorrhoeic; considered an alternative to surgery for most women |
| Tranexamic acid | Antifibrinolytic acting in endometrial capillaries; taken during menstruation | Loss down by about 50% |
| Mefenamic acid (NSAID) | Inhibits prostaglandin synthesis; anti-inflammatory and analgesic | Loss down by about 25% and period pain improved |
| Combined oral contraceptive | Suppresses ovulation and thins endometrium | Slightly lighter periods; tricycling (three packets back to back) reduces how often she bleeds |
| Progestogen-only contraceptives | Endometrial suppression | May suppress menstruation in some women |
| Cyclical oral progestogen (norethisterone) | Opposes oestrogen on the endometrium | Taken day 6 to day 26 of the cycle |
| GnRH agonist (depot) | Acts on the pituitary to stop gonadotrophin output, switching the ovaries off | Amenorrhoea; used short term, also to shrink fibroids or thin the endometrium before hysteroscopy, and to let the haemoglobin recover |
| Ulipristal acetate | Progesterone receptor modulator | Use now restricted because of rare serious liver injury; only for moderate to severe fibroid symptoms when surgery including embolisation is unsuitable or has failed |
| Oral GnRH antagonists (elagolix, relugolix, linzagolix) | Direct receptor block, taken by mouth | Effective for fibroid-related bleeding; usually with add-back hormone replacement |
The LNG-IUS is the single most effective medical treatment for heavy menstrual bleeding, better than norethisterone, the combined pill or tranexamic acid, and it also treats dysmenorrhoea, endometriosis and adenomyosis pain and protects against endometrial hyperplasia.
Tranexamic acid and mefenamic acid are not hormones. Tranexamic acid reduces bleeding but does nothing for cramps; mefenamic acid does both, but less for bleeding.
Acute heavy menstrual bleeding
Admission, intravenous access and resuscitation or transfusion, pelvic examination, full blood count, clotting screen and biochemistry, then:
- Tranexamic acid by mouth or intravenously.
- High-dose progestogen to arrest the bleeding (for example oral norethisterone 5 mg three times a day).
- GnRH analogue for medium-term suppression.
- Transvaginal ultrasound, correction of anaemia with iron or blood, immediate surgery for a cause such as a prolapsing fibroid polyp, and a longer-term plan once the diagnosis is known.
When surgery enters
Surgery is for women who no longer want fertility, where drugs have failed, or where there are pressure symptoms or prolapse. Second-generation endometrial ablation should be offered before hysterectomy; ablation suits a uterus no larger than 10 weeks' size with fibroids under 3 cm, and is only for women who have completed their family. Hysterectomy is first-line only with large fibroids plus severe pressure symptoms or associated prolapse.
Dysmenorrhoea
- Primary dysmenorrhoea is period pain with no identifiable disease, usually from menarche. Pain comes from prostaglandins and inflammatory mediators making the uterus contract strongly.
- First-line: NSAIDs (mefenamic acid, naproxen, ibuprofen), because they block the prostaglandins that cause the pain. Taking them from the start of bleeding works best.
- Hormonal contraceptives: the combined pill is widely used, though a systematic review found little evidence that it helps primary dysmenorrhoea or endometriosis pain. Progestogens given orally (desogestrel), as a depot injection (medroxyprogesterone) or as a subdermal implant (etonogestrel) can produce amenorrhoea and so relieve pain.
- LNG-IUS helps dysmenorrhoea and treats the underlying endometriosis or adenomyosis; it is often fitted at the time of laparoscopy.
- GnRH analogues are not first-line and not for long-term use in primary dysmenorrhoea because of hypo-oestrogenic effects, but there is strong evidence they relieve endometriosis pain. If pain does not settle on a GnRH analogue, hysterectomy is less likely to help either, so the drug doubles as a test.
- Heat, transcutaneous nerve stimulation, exercise and a low-fat vegetarian diet may help. Avoid codeine and opiates where possible, since they worsen coexisting bowel symptoms.
- Secondary dysmenorrhoea develops later and suggests endometriosis, adenomyosis, pelvic inflammatory disease, cervical stenosis or haematometra; treat the cause.
Premenstrual syndrome
Cyclical physical and psychological symptoms in the luteal phase that resolve as menstruation ends. Cause is unknown, but cyclical ovarian activity with the effects of oestradiol and progesterone on serotonin and GABA appears to matter. Diagnosis needs symptoms recorded prospectively over at least two cycles. Hormonal treatment works by stopping ovulation and the cyclical hormone swings.
| Line | Treatment |
|---|---|
| First | Exercise, vitamin B6 and cognitive behavioural therapy; a newer-generation combined pill, cyclically or continuously; low-dose SSRI either continuously or over days 15-28 |
| Second | Oestradiol patches with micronised progesterone or an LNG-IUS for endometrial protection; higher-dose SSRI |
| Third | GnRH analogue with add-back continuous combined hormone replacement, or tibolone |
| Fourth | Surgery (bilateral salpingo-oophorectomy with hysterectomy), with hormone replacement; a last resort, preceded by a GnRH analogue to test the expected benefit |
Progestogens alone do not treat premenstrual syndrome. The old idea that a fall in progesterone causes it is wrong, and using them may delay effective treatment.
Polycystic ovary syndrome
| Aim | Drug treatment |
|---|---|
| Protect the endometrium from unopposed oestrogen | Combined pill, cyclical oral progesterone to produce withdrawal bleeds, or the LNG-IUS |
| Hirsutism | Topical eflornithine; cyproterone acetate (an antiandrogen) |
| Insulin resistance, androgen excess, anovulation, acne, weight | Metformin, alone or added to other treatment |
| Subfertility | Letrozole first-line; clomiphene, metformin and gonadotrophins are alternatives; then laparoscopic ovarian surgery, with IVF third |
In anovulatory PCOS the endometrium is exposed to unopposed oestrogen, which is why progestogen cover or a combined pill is given: the point is endometrial protection, not just cycle control.
Endometriosis and adenomyosis
- NSAIDs for pain; they do not alter the disease.
- Combined pill, continuously or tricycled, reduces dyspareunia, dysmenorrhoea and non-menstrual pain and gives cycle control and contraception. If it works, it may be continued for years until pregnancy is wanted.
- Progestogens where the combined pill is unsuitable: depot medroxyprogesterone and the LNG-IUS give long-term benefit, especially after surgery, partly because compliance is guaranteed.
- GnRH agonists relieve symptoms well; available as a nasal spray but usually a slow-release depot injection monthly or longer. Use beyond 6 months is precluded by drug-induced osteoporosis, and symptoms return quickly after stopping. Add-back hormone replacement reduces the hypo-oestrogenic effects.
- Oral GnRH antagonists also relieve endometriosis pain and are licensed for it in some countries.
- Aromatase inhibitors block conversion of androgen to oestrogen, and aromatase is over-expressed in endometriotic tissue; still under study for resistant cases.
- Danazol suppresses ovarian function: it blocks the mid-cycle LH and FSH surge and binds androgen, progesterone and glucocorticoid receptors. It is effective in endometriosis but causes weight gain, oedema, acne with oily skin, more body hair, a deeper voice, hot flushes, headache and altered libido, and needs caution in liver disease. Its androgenic effects have pushed it out of first-line use.
Other hormonal agents to recognise
| Agent | Action | Typical use |
|---|---|---|
| Synthetic oestrogen (ethinyl oestradiol) | Inhibits the pituitary feedback loop, stopping ovulation | In most combined pills |
| Natural oestrogen (oestradiol) | Acts on bone, endometrium, skin | Hormone replacement; low-dose vaginally for urogenital atrophy |
| Progestogens | Suppress the endometrium, and ovulation in some preparations | Heavy bleeding, contraception, hormone replacement; levonorgestrel by intrauterine system |
| Tibolone | Synthetic steroid with oestrogenic, progestogenic and androgenic activity after conversion | Hormone replacement, or with long-term GnRH suppression to protect bone; improves libido |
| Clomiphene citrate | Antioestrogen at the hypothalamus and pituitary, so FSH and LH release rises and follicles grow | Ovulation induction |
| Dopamine agonists (cabergoline, bromocriptine) | Inhibit prolactin | Hyperprolactinaemia and prolactinoma causing amenorrhoea |
"Thin it, stop it, or switch it off": progestogen thins the endometrium, the pill stops ovulation, a GnRH analogue switches the ovary off.
Expect: the LNG-IUS as the most effective medical treatment for heavy bleeding with its 95% reduction and high amenorrhoea rate; the numbers for tranexamic acid (about 50%) and mefenamic acid (about 25%); the mechanism of each drug (antifibrinolytic, prostaglandin inhibition, local progestogen, pituitary suppression); cyclical norethisterone from day 6 to day 26; the 6-month limit on GnRH analogues because of bone loss and the purpose of add-back therapy; NSAIDs as first-line for primary dysmenorrhoea with the prostaglandin reason; progestogen alone being wrong for premenstrual syndrome; endometrial protection as the aim in PCOS; letrozole first-line for ovulation induction; clomiphene acting as an antioestrogen; and the androgenic side effects of danazol.
Quick revision
- Heavy bleeding: LNG-IUS first among hormonal options, about 95% less loss.
- Tranexamic acid, an antifibrinolytic, cuts loss by about half.
- Mefenamic acid blocks prostaglandins: about a quarter less loss, plus pain relief.
- Cyclical norethisterone runs day 6 to day 26.
- GnRH analogues: amenorrhoea, 6-month limit, bone loss, add-back therapy.
- Offer second-generation ablation before hysterectomy; ablation only once family is complete.
- Acute heavy bleed: tranexamic acid, high-dose progestogen, then GnRH suppression.
- Primary dysmenorrhoea: NSAIDs first, prostaglandin-driven pain.
- Premenstrual syndrome: lifestyle, cognitive therapy, vitamin B6, combined pill, SSRI; not progestogen alone.
- PCOS: protect the endometrium; letrozole for ovulation induction; metformin for metabolic features.
- Danazol works in endometriosis but is androgenic; clomiphene is an antioestrogen.
Written by The House Job from standard references (Gynaecology by Ten Teachers; Basic and Clinical Pharmacology by Katzung).
FAQ
Why is a progestogen-releasing intrauterine system so much better than tablets for heavy bleeding?
It delivers progestogen straight to the endometrium, producing marked atrophy with few systemic effects, and compliance is automatic once it is fitted.
What is add-back therapy?
Low-dose oestrogen with progestogen, or tibolone, given alongside a GnRH analogue to prevent hot flushes and bone loss from the induced low-oestrogen state.
Why are NSAIDs first-line for period pain rather than painkillers such as paracetamol?
Period pain is driven by endometrial prostaglandins, and NSAIDs block their synthesis, so they treat the mechanism rather than just the pain.
Which menstrual problems does the combined pill genuinely help?
It lightens periods, regulates irregular cycles, helps acne and hirsutism and premenstrual symptoms, and lowers the risk of ovarian and endometrial cancer; its benefit in primary dysmenorrhoea is less well supported.