Absent periods (secondary amenorrhea): causes and step-by-step work-up

This definition has practical significance: a woman who has always had irregular cycles (say every 45-60 days) may have periods less often and still not have amenorrhea by definition. Conversely, a woman with regular cycles whose period has not come for three months should be examined. It is also worth remembering that withdrawal bleeding after hormonal drugs (for example after contraceptive pills) is not proof that her own hormonal axis is working properly.

The commonest cause of secondary amenorrhea in a woman of reproductive age is pregnancy, so the first test is a urine pregnancy test or a blood beta-hCG. This step applies to every woman, including one using contraception, because no method gives a hundred percent certainty. Only after pregnancy has been excluded are other causes sought.

Physiological causes also include breastfeeding (especially exclusive breastfeeding, which suppresses ovulation) and menopause. Induced causes include the use of certain medicines: hormonal contraception (for example the levonorgestrel intrauterine system, injections, an implant), antipsychotics that raise prolactin, and chemotherapy or pelvic radiotherapy. With hormonal drugs, absent bleeding is often an intended or acceptable effect, but it needs discussing with a doctor if it causes worry.

This division organises the causes by level of the hormonal axis: hypothalamus, pituitary, ovaries, and uterus with outflow tract. In practice several causes can coexist, for example PCOS and an energy deficit in a woman who trains hard. That is why the result of a single test does not end the work-up: it must always be combined with the history.

The mechanism of FHA is that the hypothalamus, receiving signals of energy deficit or stress, reduces GnRH secretion, and consequently the pulsatile secretion of LH and FSH falls, the ovaries stop maturing follicles, and the estradiol level declines. It is a kind of saving of resources: fertility is switched off when the body judges conditions unfavourable. Risk factors include restrictive diets, eating disorders, intense sport (especially weight-class and endurance disciplines), great psychological stress, chronic illness and rapid weight loss. It should be remembered that FHA can also occur in women of normal body weight.

Both excess prolactin and thyroid disease are among those causes of absent periods that are easy to detect with a simple blood test and are often reversible. Prolactin inhibits GnRH secretion, so a raised level can halt ovulation and menstruation. The Endocrine Society guideline on hyperprolactinaemia covers assessing the cause (including drugs, hypothyroidism, pituitary tumours), treatment of drug-induced hyperprolactinaemia and management of prolactinomas. Some causes of a slight rise in prolactin without a tumour are discussed in our article on raised prolactin without a tumour.

Thyroid disease, both underactive and overactive, disturbs ovulation and cycle regularity. That is why TSH belongs to the initial set of tests in amenorrhea, as in other cycle disorders, which we also mention in the articles on spotting and heavy periods. The interpretation of TSH and thyroid hormones is described in our entry on TSH, and prolactin in the entry on the prolactin test.

POI means loss of normal ovarian function before the age of 40. It presents with irregular cycles or absent periods, often with symptoms of oestrogen deficiency (hot flushes, vaginal dryness, sleep and mood disturbances) and raised FSH. Unlike menopause, it does not always mean complete and irreversible loss of ovarian function: Klein et al. note that women with POI can have unpredictable ovarian function and may therefore require contraception or infertility services. Because of the consequences for bones and the circulation, the diagnosis of POI requires specialist care and consideration of hormone replacement therapy. Other markers of ovarian reserve are discussed in our article on low AMH.

Adhesions in the uterine cavity (Asherman syndrome) can arise after curettage of the uterine cavity, uterine surgery or severe infections and cause scanty periods or complete absence of periods despite normal hormones. A clue is a period that disappeared after a procedure, and normal hormone levels, including FSH and estradiol, in the absence of bleeding. Diagnosis rests on imaging and hysteroscopy. In the meta-analysis the adhesions were mostly mild and the authors considered their clinical significance unknown, but this cause needs a different work-up from the hormonal one, so it is worth remembering after any uterine procedure.

Outflow tract causes also include narrowing of the cervix after procedures. Cyclical lower abdominal pain without bleeding suggests retention of menstrual blood and needs urgent gynaecological assessment. Many of these causes can be treated surgically.

This scheme is consistent with the recommendations described in the review by Klein et al. and with the ASRM committee, which in 2024 published an updated opinion on the evaluation of amenorrhea, replacing the 2008 document. The practical rule is: simple, inexpensive tests first, and imaging and genetic tests only when symptoms or results point to them.

Chronic oestrogen deficiency, whatever its cause, weakens the bones. In FHA the Endocrine Society guideline points to bone loss as one of the main complications, and in POI the guideline lists bone and the cardiovascular system among the main sequelae. This applies especially to young women, because peak bone mass is reached in the teenage years and young adulthood. Bone lost in that period may not fully recover, so early diagnosis matters. We write about osteoporosis in our entry on osteoporosis.

As for fertility: in many causes (FHA, hyperprolactinaemia, PCOS, thyroid disease) ovulation can be restored after treating the cause, so absent periods do not mean permanent infertility. Women with POI can have unpredictable ovarian function; the guideline and the practical review recommend a discussion of contraception and fertility. If you are planning a pregnancy, do not wait for periods to return by themselves without a diagnosis.

Absent periods for longer than three months are information, not a convenience. We recommend starting with a pregnancy test, then doing the basic hormone set (TSH, prolactin, FSH, LH) and supplementing it with a history of body weight, exercise and stress. The guidelines agree that many causes can be treated and that protecting the bones and discussing fertility are important. The worst thing to do is to wait in the hope that the period will return by itself, especially when an energy deficit stands behind the absence.