PCOS / PMOS
PCOS and functional hypothalamic amenorrhea
The diagnosis that can hide
Female athletes often have cycle disorders, and polycystic ovary syndrome (PCOS/PMOS) is not the only reason. The cycle can also be disturbed by a lack of energy, not only in athletes but in any woman on a strict diet or under strong stress. After pregnancy, functional hypothalamic amenorrhea and PCOS are the two most common causes of secondary amenorrhea.
The two conditions have opposite mechanisms and need different treatment. In tests, however, they often look alike, they can exist together, and a woman can move from one to the other. For this reason, the diagnosis needs particular care.
What is functional hypothalamic amenorrhea?
The hypothalamus, a small area of the brain, controls the cycle with pulses of the hormone GnRH. When the body does not have enough energy or is under strong stress, the hypothalamus slows these pulses down. LH and FSH fall, the ovaries do not produce enough estrogen, and ovulation stops. The three most common causes are restrictive eating or dieting, intense physical exercise and psychological stress. Often all three come together. More in the article “Eating disorders”.
The condition covers a wide spectrum. It starts with changes that are not noticed, such as a short luteal phase or cycles without ovulation that have a normal length. It continues with mild cycle disorders and goes as far as the complete loss of periods. In a study of women who exercise, 50% of the cycles showed such changes: 29% had a luteal phase defect, and 21% had no ovulation. In women who did not exercise, the figure was 4%. In some women, periods stop for six months, a year or even longer.
Since 2023, the International Olympic Committee has described energy deficiency in sport as a syndrome of its own (Relative Energy Deficiency in Sport, REDs). A lack of energy does not always mean an eating disorder. It often happens unintentionally, when food intake does not rise as much as training does. Depending on the study, signs of energy deficiency are found in 23-80% of female athletes. The effects are not limited to the cycle. They also affect the bones, metabolism, the heart, digestion, sleep, mental health and performance.
Amenorrhea is therefore not a normal “price” of training. It is a sign that the body is saving energy at the expense of health. According to the 2017 Endocrine Society guideline, the doctor should assess every woman with cycles longer than 45 days or with amenorrhea of three months or more.
How do the two mechanisms differ?
In the syndrome, the hypothalamus sends fast pulses. LH is often raised, estrogen is normal, and androgens are raised. In functional hypothalamic amenorrhea, the pulses are slow. LH is low or normal, estrogen is low, and androgens are low or normal. In the syndrome, periods are usually rare, while in functional hypothalamic amenorrhea they often stop completely.
Two causes, opposite mechanisms
Polycystic ovary syndrome
Functional hypothalamic amenorrhea
How can the two be told apart?
On ultrasound, the two conditions often look alike. A 2024 review in Human Reproduction Update summarized the available studies. About 42-47% of women with functional hypothalamic amenorrhea have polycystic ovaries, compared with about 30% in the general population. AMH does not help to tell them apart. In functional hypothalamic amenorrhea, it can be raised, normal or low, depending on how much the body compensates and how FSH works.
In women with functional hypothalamic amenorrhea and polycystic ovaries, the criteria of the fourth phenotype of PCOS (phenotype D) are met at the same time: rare or absent ovulation and polycystic ovaries, without raised androgens. For this reason the diagnosis needs care, because many women diagnosed with PCOS in fact have functional hypothalamic amenorrhea. The Endocrine Society points out that this may apply to up to 50% of the women diagnosed with PCOS without raised androgens. PCOS is a diagnosis of exclusion.
The distinction is based on several findings together. The first is the history: diet, hours of training, recent weight loss, stress and the way the cycle has changed. The second is the hormones. Low estradiol and a low or normal LH point to functional hypothalamic amenorrhea. The ratio of LH to FSH is below 1 in about 82% of women with functional hypothalamic amenorrhea, while a ratio above 2 is typical of the syndrome. Raised androgens and extra hair growth point to the syndrome. The progestin challenge test is not enough to tell them apart, because even women with functional hypothalamic amenorrhea can bleed after the test.
Hormonal contraception hides both conditions. An athlete who takes the pill has regular bleeding. This bleeding, however, shows neither whether her body has enough energy nor whether she has the syndrome.
What happens when both conditions exist together?
The two conditions do not exclude each other. A woman with the syndrome can develop functional hypothalamic amenorrhea when she follows a strict diet, trains intensely or goes through a period of great stress. The hypothalamus then slows down, LH and androgens fall, and the features of the syndrome fade. The syndrome “hides” behind the amenorrhea.
When energy is restored, the hypothalamus recovers. In these women, however, the cycle does not become regular. Periods become rare, and extra hair growth or acne appear or return. The syndrome becomes visible. In an analysis of women with functional hypothalamic amenorrhea and polycystic ovaries, about 10% had features of the syndrome. In another study, 6 of 120 women developed the picture of the syndrome during treatment with pulsatile GnRH.
A woman can therefore move from one form to the other during her life, depending on diet, training, weight and stress. The diagnosis is not a fixed label. The doctor reassesses it every time the picture changes. The data on this transition come mainly from small studies, and long-term studies are still missing.
From one form to the other
When energy is not enough
Cause
Strict diet, intense training, stress.
What happens
The hypothalamus slows down, and LH and androgens fall.
Result
Periods stop, and the syndrome “hides”.
When energy is restored
Cause
Enough food and adapted training.
What happens
The hypothalamus recovers, and LH rises.
Result
Periods become rare, hair growth or acne appear, and the syndrome becomes visible.
The data
Polycystic ovaries in 42-47% of women with functional hypothalamic amenorrhea. Features of the syndrome in about 10% of them.
Why does the right diagnosis change the treatment?
In functional hypothalamic amenorrhea, the treatment is to restore energy: more food, less or different training and better handling of stress. Weight gain is often needed as well. The Endocrine Society recommends cognitive behavioral therapy. The pill does not treat the condition. It brings bleeding, but it does not protect the bones and it hides the return of the cycle. If the cycle does not return after a reasonable period of change, the doctor can give estradiol through the skin with a cyclic progestin for a short time.
In the syndrome, the doctor often recommends weight loss and more exercise. In an athlete with the syndrome, the same advice can lead to energy deficiency and functional hypothalamic amenorrhea. For this reason, the doctor first assesses how much energy the woman has available, and only then recommends a diet or more training.
The difference also matters when a woman wishes to have a child. In functional hypothalamic amenorrhea, pulsatile GnRH is the first choice where it is available. In women with functional hypothalamic amenorrhea and polycystic ovaries, gonadotropins more often cause an excessive response of the ovaries. In one study, 34% of cycles with gonadotropins were cancelled for this reason, compared with 14% with pulsatile GnRH. The doctor induces ovulation only when the body mass index is at least 18.5 and energy has been restored. More in the article PCOS and infertility.
What happens to the bones?
Puberty and the first years of adult life are the time when the body builds its peak bone mass. In functional hypothalamic amenorrhea, low estrogen and the lack of energy lower bone density and increase the risk of stress fractures. In athletes who trained more than 12 hours a week, in a sport where low weight matters, and restricted their food, 46% had stress fractures. The Endocrine Society recommends measuring bone density after six months of amenorrhea.
In the syndrome, androgens seem to protect the bones. In women with functional hypothalamic amenorrhea and polycystic ovaries, bone density in the spine was better (T-score −1.1 compared with −1.9). This protection, however, is not complete, and amenorrhea needs treatment in these women as well.
The practice's approach
The doctor asks every woman with a cycle disorder about diet, training, weight changes and stress. The doctor always considers both diagnoses, PCOS and functional hypothalamic amenorrhea, and reassesses the diagnosis when the picture changes.
Treatment is necessary and always individual. Close cooperation with dietitians, sports medicine and psychology improves quality of life and prevents long-term effects on the bones, the heart and fertility. The goal of the practice is a working cycle and healthy bones.
Sources: Gordon CM et al., Functional hypothalamic amenorrhea: an Endocrine Society clinical practice guideline, Journal of Clinical Endocrinology and Metabolism 2017. Mountjoy M et al., 2023 International Olympic Committee’s (IOC) consensus statement on Relative Energy Deficiency in Sport (REDs), British Journal of Sports Medicine 2023. Ott J, Robin G, Hager M, Dewailly D, Functional hypothalamic amenorrhoea and polycystic ovarian morphology: a narrative review about an intriguing association, Human Reproduction Update 2024. Robin G et al., Polycystic ovary-like abnormalities (PCO-L) in women with functional hypothalamic amenorrhea, Journal of Clinical Endocrinology and Metabolism 2012. De Souza MJ et al., High prevalence of subtle and severe menstrual disturbances in exercising women, Human Reproduction 2010. Hagmar M et al., Hyperandrogenism may explain reproductive dysfunction in Olympic athletes, Medicine & Science in Sports & Exercise 2009. International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome (Monash University, ESHRE, ASRM, 2023).