Amenorrhea: Pathology review

Definitions & Key takeaways

Amenorrhea is the absence of menstrual periods in a woman of reproductive age. There are two types of amenorrhea: primary and secondary. Primary amenorrhea is defined as the failure to achieve menarche by age 16 in the absence of any secondary sexual characteristics, or by 14 if there are secondary sexual characteristics present. Secondary amenorrhea is defined as a cessation of menses for 3 months in a woman with previously established normal menstrual cycles.

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Case study0:00–1:20

Two people come to the clinic one day. First you see Ana, a 17 year old teenage girl.
Ana comes with her mother, who’s worried because Ana hasn’t had her first period yet. Upon physical examination, you notice that Ana is quite short for her age.
In addition, she has a wide neck, broad chest, and poorly developed breasts with widely spaced nipples. You decide to perform a blood test, which reveals low estrogen levels and high FSH and LH.
Next, comes María, a 25 year old female who’s concerned because she hasn’t had her period for nine months now. She’s sexually active, so the first thing you do is ask for a pregnancy test, which comes up negative.
When asked about physical activities, she refers to going for a 2-hour run every single day, plus swimming and then tennis on weekdays.
Regarding her diet, she’s very strict when it comes to avoiding fatty foods. On physical examination, you realize that María is underweight, and a blood test reveals low levels of estrogen, LH, and FSH.
Okay, now both Ana and María have amenorrhea, which is generally defined as the absence of menstruation in females of reproductive age.

Physiology1:20–6:55

Now, for menstruation to happen, an individual must have a regular female reproductive anatomy and sexual development, which is normally under control of the hypothalamic-pituitary-gonadal axis.
First, the hypothalamus secretes gonadotropin-releasing hormone, or GnRH for short, which goes to the anterior pituitary to stimulate the release of gonadotropic hormones, which are luteinizing hormone or LH, and follicle-stimulating hormone or FSH.
LH and FSH then stimulate the gonads to produce sex hormones; in females, LH and FSH stimulate the ovaries to secrete estrogen and progesterone, which are responsible for the female primary sexual characteristics.
These are the changes necessary for reproduction, including menstruation, ovulation, and uterine development. LH and FSH are also responsible for the development of secondary sex characteristics that aren’t required for reproduction, like breast development, hip widening, and hair growth mainly on the axillae and genital areas.
Now, once sex hormones have done their job, they signal the hypothalamus and pituitary to turn off the secretion of GnRH, FSH, and LH.
Menarche, which refers to the first menstrual period, occurs during early adolescence or puberty, usually by the age of 15.
Following menarche, the menstrual cycle recurs on a monthly basis until a person reaches menopause, pausing only during pregnancy.
The monthly menstrual cycle can vary in duration from 20 to 35 days, with an average of 28 days. Each menstrual cycle begins on the first day of menstruation, and this is referred to as day one of the cycle.
During the menstrual cycle, the ovaries and the endometrium each undergo their own set of changes, which are separate but related.
Now, the first two weeks of the menstrual cycle is called the preovulatory or follicular phase, and this corresponds to the menstrual and proliferative phases of the endometrium.
During this phase, the pituitary mainly secretes FSH, which stimulates follicles scattered throughout the ovaries to start developing and secreting estrogen.
The increased estrogen levels act as a negative feedback signal, telling the pituitary to secrete less FSH. As a result, some of the developing follicles in the ovary will regress and die off.
However, the follicle that has the most follicle stimulating hormone receptors, will continue to grow, becoming the dominant follicle that will eventually undergo ovulation.
Now, estrogen levels start to steadily climb higher and higher, the estrogen from the dominant follicle now becomes a positive feedback signal; that is, it makes the pituitary secrete a whole lot of FSH and especially LH.
This surge stimulates ovulation, which is the rupture of the dominant follicle to release the oocyte, so the secretion of estrogen decreases.
Meanwhile, the uterus is preparing the endometrium for implantation and maintenance of pregnancy. This process begins with the menstrual phase, which is when the old endometrial lining from the previous cycle is shed and eliminated through the vagina, producing the bleeding pattern known as the menstrual period.
The menstrual phase is followed by the proliferative phase, during which high estrogen levels stimulate thickening of the endometrium, as well as emergence of spiral arteries to feed the growing functional endometrium.
Following ovulation, the remnant of the ovarian follicle becomes the corpus luteum. So the two weeks following ovulation is referred to as the postovulatory or luteal phase.
This corresponds to the secretory phase of the endometrium, where the uterine glands begin to secrete more mucus. Now, the corpus luteum secretes estrogen, which rises again, as well as lots of progesterone, which acts as a negative feedback signal on the pituitary, decreasing release of FSH and LH.
Over time, the corpus luteum gradually degenerates into the nonfunctional corpus albicans. The corpus albicans doesn’t make hormones, so estrogen and progesterone levels slowly decrease.
When progesterone reaches its lowest level, the spiral arteries collapse, and the endometrium prepares to shed through menstruation.
This shedding marks the beginning of a new menstrual cycle and another opportunity for fertilization. Okay now, amenorrhea can be classified as primary or secondary.

Pathology6:55–9:00

Primary amenorrhea is when a female over the age of 15 hasn’t had her first menstruation, or menarche, despite normal growth and development of secondary sexual characteristics; or when a female over the age of 13 has neither had her menarche nor developed any secondary sexual characteristics.
For your exams, some high yield causes of primary amenorrhea include Turner syndrome, müllerian agenesis, and imperforate hymen.On the other hand, secondary amenorrhea is when a female who used to have regular menstrual cycles stops having them for at least three consecutive months, or for six months in a female who used to have irregular menstrual cycles.
Most often, secondary amenorrhea is caused by natural processes, such as pregnancy, menopause, and breastfeeding. However, in some cases, secondary amenorrhea can be caused by an underlying disorder.
For your exams, the most important is a hormonal imbalance at any level of the hypothalamic-pituitary-ovarian axis, such as functional hypothalamic amenorrhea; hyperprolactinemia; and polycystic ovarian syndrome or premature ovarian failure.
Other less frequently tested hormonal disorders that may cause secondary amenorrhea include Cushing syndrome, which is an endocrine disorder that involves high levels of cortisol; as well as thyroid disorders like hyperthyroidism, where the thyroid gland produces too much thyroid hormones, or hypothyroidism, where the thyroid doesn’t make enough hormones.
Now, keep in mind that all these underlying disorders may also occur before menarche, in which case they would lead to primary amenorrhea.All right, so let’s dive into the causes of primary amenorrhea.

Turner syndrome9:00–12:47

The most common cause is Turner syndrome, which is characterized by having 45 chromosomes with only one X chromosome. In most cases, this happens when a nondisjunction event occurs during meiosis of the paternal gamete, so that the sperm cell lacks a sex chromosome.
Conversely, if the nondisjunction occurs after formation of the zygote during mitosis, the result is a mosaic karyotype, meaning that some cells are 45,X and others are 46,XX.For your exams, you should recognize some clinical features that are characteristic for Turner syndrome.
Firstly, infants may have a variety of congenital malformations. These can include a horseshoe kidney, which is when the two kidneys fuse at the bottom, forming a U shape; as well as cardiovascular abnormalities, like bicuspid aortic valve and coarctation or narrowing of the aorta, which are the most common causes of death in childhood.
Another very common finding in infants are lymphatic defects, such as lymphedema or swelling of the hands and feet. Many also develop a cystic hygroma, which is an abnormal swelling on the back of the baby’s neck due to lymphatic fluid build up, which eventually decreases as they age.
This often leaves extra skin on the neck, called a webbed neck that’s wider than normal. Additionally, mosaic individuals with some 46,XY cells are at increased risk for gonadoblastoma, which is a complex neoplasm of gonadal components.
Now, the X chromosome also carries genes that are important for growth and development of tissues throughout the body. One of these is the short stature homeobox - SHOX for short - gene.
So having a single copy of the SHOX gene results in, you guessed it, short stature. Other characteristic features include a shield chest, which is when the individual has a broad chest and extensively spaced nipples.
Additional features include shortened fourth metacarpals or ring fingers, low set ears, and arms that turn outward at the elbows, also called cubitus valgus.During puberty, there’s minimal pubic hair, breast, and uterine development, as well as ovarian dysgenesis or abnormal development, leading to streak ovaries, which develop white atrophic fibrous strands.
As a result, females with Turner syndrome produce decreased levels of estrogen, which leads to increased levels of both LH and FSH.Because of this, Turner syndrome is the most common cause of primary amenorrhea, and thus individuals are said to reach ‘menopause before menarche’.
As a consequence, many females with Turner syndrome are infertile. Keep in mind though that pregnancy may be possible in some cases through in-vitro fertilization or treatment with exogenous estradiol-17β and progesterone.Diagnosis of Turner syndrome can be confirmed via karyotype analysis, and treatment usually involves growth hormone therapy during childhood to promote bone growth, as well as sex hormone replacement therapy starting at puberty to promote breast and uterine development.Moving on, the second most common cause of primary amenorrhea is Müllerian agenesis, which is also called Mayer-Rokitansky-Kuster-Hauser syndrome.

Müllerian agenesis12:47–14:17

Okay, normally, during the first trimester of fetal life of a female baby, there’s a pair of ducts, called the paramesonephric or Mullerian ducts, which develop into the uterus, cervix, and upper two thirds of the vagina.
In Müllerian agenesis, the Müllerian ducts don’t develop properly. As a result, these organs may be absent, or rudimentary and obstructed, leading to primary amenorrhea, as well as dyspareunia, or painful sexual intercourse, and infertility.
However, the ovaries develop normally, and the hypothalamic-pituitary-ovarian axis is perfectly functional. So individuals with Mullerian agenesis have fully developed secondary sexual characteristics, and this is a key difference from Turner syndrome.
Now, for diagnosis of Müllerian agenesis, an ultrasound can show if there are anatomical abnormalities involving the uterus or vagina, and treatment usually aims at correcting some anatomical issues using vaginal dilators or surgery.
Another rare but frequently tested cause of primary amenorrhea is an imperforate hymen. Typically, the hymen is a thin half moon shaped membrane that partially covers the external opening of the vagina.

Imperforate hymen14:17–15:46

Now, an imperforate hymen results when the hymen central epithelial cells fail to degenerate during fetal development. This leaves a hymenal membrane that completely covers the vaginal opening, blocking it.
At birth, an imperforate hymen may cause vaginal mucus to build up, causing the hymenal membrane to bulge outwards. Fortunately, that’s usually self-resolving!
The most high yield symptom occurs during puberty, when there’s primary amenorrhea because menstrual blood can’t flow out of the vagina.
As a result, menstrual blood accumulates in the vagina, which is also known as hematocolpos. A test question may sometimes include a characteristic picture of a bulging, bluish hymenal membrane.
What’s important to note here is that individuals do experience recurring menstrual cramps and abdominal or pelvic pain, since they do have a normal menstrual cycle.
To confirm the diagnosis, an ultrasound can be done to spot the hematocolpos. Treatment is with surgical incision of the hymen.All right, now let’s take a look at some causes of secondary amenorrhea.

Menopause15:46–17:49

A natural cause you must absolutely remember is menopause, which is the permanent stopping of menstrual cycles. To be more specific, menopause is officially diagnosed after twelve months of amenorrhea, so when an entire year has passed since the last menstrual period.This usually happens at around the age of 50, but keep in mind that it could occur earlier in smokers.
Now, menopause is usually preceded by perimenopause, which is a transition period that typically lasts about four to five years.
During perimenopause, the ovaries have a lot less functional follicles, so there may be abnormal menstrual cycles characterized by irregular or missed periods.
And fewer follicles also means less production of estrogen and progesterone, so less inhibition on the hypothalamus and the pituitary.
In turn, the hypothalamus and pituitary produce more GnRH, LH, and especially FSH. These hormonal changes can cause a bunch of symptoms like hot flashes and night sweats, which can lead to sleep disturbances.
In addition, individuals may experience vaginal atrophy and dryness, which can lead to dyspareunia; as well as hirsutism, which refers to an excessive body hair growth in a male-like pattern that mainly involves the face, chest, and back.
Finally, estrogen normally has a protective effect on both the cardiovascular system as well as the skeleton. So, low levels of estrogen can lead to complications like coronary artery disease and osteoporosis.
The good news is that the body can adjust to the hormone changes, so they actually go away on their own after a couple of years.
In the meantime, menopausal hormone therapy can help alleviate these symptoms.Switching gears, secondary amenorrhea can also indicate that there’s an underlying disorder, especially if it occurs before the age of 50.

Functional hypothalamic amenorrhea17:49–20:03

A very high yield one is functional hypothalamic amenorrhea, where the hypothalamus fails to properly secrete GnRH in a pulsatile manner.
As a result, there’s dysfunction of the hypothalamic-pituitary-ovarian axis, which ultimately affects the menstrual cycle.
Now, functional hypothalamic amenorrhea is also commonly called exercise-induced amenorrhea, since it is often caused by severe caloric restriction, as well as prolonged periods of strenuous exercise.
So in a test question, look for training athletes who are over-exercising, or individuals with eating disorders, nutritional deficiencies such as an excessively low fat consumption, as well as those who have been through serious physical or emotional stress.
That’s because low fat consumption inhibits leptin secretion, which would normally help stimulate hypothalamic GnRH secretion.
On the other hand, over-exercising and stress stimulates the adrenal gland to release more cortisol, which instead inhibits GnRH secretion.
For your exams, the most characteristic symptoms of functional hypothalamic amenorrhea can be remembered as the female athlete triad, which includes low energy availability; decreased bone mineral density, which puts these individuals at higher risk for osteoporosis and fractures; and menstrual dysfunction, which leads to infertility.
To confirm the diagnosis, a blood test would show low levels of GnRH, LH, FSH, and estrogen, as well as low levels of leptin and high levels of cortisol.
Treatment of functional hypothalamic amenorrhea includes lifestyle changes, such as weight gain, and adequate caloric intake for the level of exercise.
Psychotherapy can also be useful to help individuals cope with stress. Secondary amenorrhea can also be due to hyperprolactinemia, or high levels of prolactin in blood.

Hyperprolactinemia20:03–23:26

This typically occurs when the pituitary lactotroph cells secrete more prolactin than usual. The most common cause is physiologic hyperprolactinemia, which happens during pregnancy and lactation.
However, there’s also pathologic causes of hyperprolactinemia. For your exams, a very high yield cause is a type of pituitary adenoma called prolactinoma; this is a benign tumor of lactotroph cells, which grow uncontrollably and make excess amounts of prolactin.Now, bear in mind that lactotroph cells are under constant inhibition by dopamine, which is secreted by the hypothalamus; whereas the rest of the pituitary cells work under hypothalamic stimulation.
So with tumors that compress the pituitary stalk, like craniopharyngioma, dopaminergic inhibition is lost, leading to uncontrolled prolactin secretion.
On the other hand, the other pituitary cells lose their hypothalamic stimulation. So with these tumors there’s hyperprolactinemia associated with hypopituitarism, which means the pituitary gland doesn’t produce enough of its other hormones.
Last but not least, hyperprolactinemia can also be caused by certain anti-dopaminergic medications. For your exams, the most important medications to remember are typical antipsychotics like haloperidol, and atypical antipsychotics like risperidone, as well as antiemetics like metoclopramide, and antihypertensives like methyldopa or reserpine.
Now, high levels of prolactin inhibit the release of GnRH from the hypothalamus, resulting in decreased LH and FSH. In turn, these decreased hormone levels lead to decreased estrogen levels.
In individuals who are biologically female, this can stop ovulation and menstruation, resulting in amenorrhea and infertility.
Prolactin also stimulates the production of breast milk, so there’s usually galactorrhea or milky nipple discharge. And finally, the low estrogen levels can also lead to osteoporosis.
Keep in mind that hyperprolactinemia in males can cause erectile dysfunction. And that’s a high yield fact!
Diagnosis of hyperprolactinemia can be confirmed with blood tests, which reveal high prolactin levels in the blood. If a prolactinoma is suspected, it can be detected with imaging studies like MRI, and on a biopsy, you'd see hyperplasia of lactotroph cells.
Treatment of hyperprolactinemia varies based on the underlying cause, but it generally involves giving dopamine agonists, such as bromocriptine or cabergoline, to inhibit prolactin secretion.
If there’s a prolactinoma, surgery may be needed. Another condition is polycystic ovarian syndrome, or PCOS for short, which seems to be due to an imbalance in the hypothalamic-pituitary-ovarian axis.

Polycystic ovarian syndrome23:26–27:53

Now, what causes this imbalance is not well understood, but it’s thought to be related to insulin resistance, which is when the cells in the liver, adipose tissue, and muscles become insensitive to insulin, so they’re less able to pull in glucose from the bloodstream.
Not one to give up, the persistent pancreas secretes more and more insulin, until it can get those cells’ attention. Now, what’s important is that insulin receptors are also present on the theca cells that surround the ovarian follicle.
So the excess insulin can cause them to grow and divide, and more cells means more LH receptors. Somehow, it’s thought that the hypothalamus responds by speeding up its pulses of GnRH, so that more LH is made by the pituitary.
This leads to an increase in the production of LH compared to FSH. Now, constantly high levels of LH lead to an increased stimulation of the theca cells, which in turn increase their production of androstenedione, which is later converted into androgens, like testosterone.
In addition, the high LH results in a decreased rate of follicular maturation, so the dominant follicle can’t rupture to release the oocyte.
As a consequence, ovulation doesn’t occur, which is called anovulation. Now, the follicle may degenerate, or it may remain there, appearing as a cyst.
Over time, the ovaries can end up having a bunch of unruptured follicles or cysts. For your exams, you should be able to recognize some tell-tale signs of PCOS.
Typically, the high levels of androstenedione lead to hirsutism, or hair growth on the chin and upper lip, chest, and back; as well as male-pattern baldness, meaning a thinning of the hair starting from the crown of the head.
It can also lead to acne, which often involves the face, chest, and back. On the other hand, anovulation can cause amenorrhea, or oligomenorrhea, meaning infrequent and irregular menstrual periods, so remember that PCOS is one of the most common causes of infertility.
In addition, because there’s repeated anovulatory cycles in PCOS, the ovaries don't go into a luteal phase. As a result, the ovarian follicles keep secreting estrogen, but also there’s no corpus luteum to secrete the progesterone needed to counteract its effects on the endometrium.
So the endometrium remains in the proliferative phase, and over time, this can lead to endometrial hyperplasia and an increased risk of endometrial cancer.
Finally, those with insulin resistance may be overweight or obese, and may develop acanthosis nigricans, which are dark, velvety patches in the creases of the neck, underarms, and groin.A diagnosis of PCOS typically is made when there’s an elevated LH to FSH ratio, as well as high androgen levels in the blood.
In addition, a pelvic ultrasound may reveal enlarged ovaries that contain multiple unruptured follicles that look like small cysts.
Although these findings aren’t necessary for the diagnosis, you should definitely remember them for your exams.Most often, treatment of PCOS involves weight loss and oral contraceptives to help regulate the menstrual cycle, as well as to prevent endometrial hyperplasia and cancer.
For those who desire to become pregnant, clomiphene can help induce ovulation. Finally, hirsutism can be treated with anti-androgen medications, such as spironolactone, finasteride, or flutamide.Our final cause of secondary amenorrhea is primary ovarian insufficiency, also called premature ovarian failure.

Primary ovarian insufficiency27:53–30:30

This is when the ovarian follicles stop functioning in females of reproductive age, resulting in early menopause before the age of 40.
In the majority of cases, primary ovarian insufficiency is idiopathic, so there’s no clear cause. In other cases, the ovaries can get harmed by chemotherapy, radiotherapy, or autoimmune destruction.
Finally some cases can be linked to a chromosomal abnormality like Turner syndrome or Fragile X syndrome, especially when primary ovarian insufficiency occurs before the age of 30.
There are two proposed mechanisms for the explanation of how primary ovarian insufficiency develops. The first mechanism is that there are few or no remaining follicles in the ovary; this could be because the ovary started out with only a few or because a lot of them degenerated too quickly.
The second mechanism is that the follicles are dysfunctional. As a result, the ovaries fail to respond to LH and FSH, meaning they can’t ovulate in a typical fashion and they produce less hormones, mainly estrogen.
The pituitary gland attempts to restore balance by increasing production of LH and FSH, and this is called hypergonadotropic hypogonadism.
Most individuals will experience puberty with regular menstrual cycles before the disorder develops. Once primary ovarian insufficiency occurs, symptoms include anovulation, amenorrhea, and infertility.
In addition, individuals may experience early signs of menopause, such as hot flashes, night sweats, and vaginal dryness.
But, unlike menopause, some individuals are still able to get spontaneously pregnant because they may have intermittent ovarian function.
Diagnosis can be done by detecting low blood levels of estrogen and high levels of FSH and LH. In addition, a karyotype screening is also needed to look for chromosomal abnormalities.
The main treatment for primary ovarian insufficiency is hormone replacement therapy. For individuals who are struggling to become pregnant, in vitro fertilization can be used.All right, as a quick recap… Amenorrhea is the abnormal absence of menstruation in females of reproductive age.

Review30:30–35:40

Primary amenorrhea is when a female over the age of 15 hasn’t had her menarche, despite normal development of secondary sexual characteristics; or when a female over the age of 13 has neither had her menarche nor developed any secondary sexual characteristics.
Turner syndrome affects individuals that have a 45,X karyotype. This results in ovarian dysgenesis with streak ovaries, which often causes primary amenorrhea and infertility, as well as decreased levels of estrogen, which leads to increased levels of both LH and FSH.
Important clinical features include a short stature, a webbed neck, and a shield chest. In addition, there can be congenital malformations such as a horseshoe kidney, bicuspid aortic valve and coarctation, and lymphatic defects.
Now, Müllerian agenesis, is when the Müllerian duct system doesn’t develop properly and therefore, the uterus, cervix and upper two thirds of the vagina, may be absent, or rudimentary and obstructed, resulting in dyspareunia, and infertility.
Since they have functional ovaries, estrogen and progesterone levels are normal, as well as FSH and LH levels, secondary sexual characteristics are fully developed.
Finally, a rare but frequently tested cause of primary amenorrhea is an imperforate hymen, where the hymenal membrane completely covers the vaginal opening, blocking it.
During puberty, individuals present with hematocolpos and a bulging, bluish hymenal membrane, associated with menstrual cramps.
On the other hand, secondary amenorrhea is when a female who used to have regular menstrual cycles stops having them for at least three consecutive months, or for six months in a female who used to have irregular menstrual cycles.
A natural cause of secondary amenorrhea is menopause, which causes the permanent stopping of menstrual cycles at around the age of 50, and is usually preceded by four to five years of perimenopause, which is characterized by decreased production of estrogen and progesterone, as well as increased production of GnRH, LH, and FSH.
This results in abnormal menstrual cycles, hot flashes, and sleep disturbances, as well as vaginal atrophy and hirsutism, and can lead to complications like coronary artery disease and osteoporosis.
Now, secondary amenorrhea can also indicate an underlying disorder. Functional hypothalamic amenorrhea is when there’s a functional disruption of the pulsatile GnRH secretion, often due to weight loss from severe caloric restriction, strenuous exercise, or stress.
There’s low levels of LH, FSH, estrogen, and cortisol, which leads to the female athlete triad of low energy availability, menstrual dysfunction, and decreased bone mineral density.
Another cause of secondary amenorrhea is hyperprolactinemia, which can be physiologic during pregnancy or lactation; or have pathologic causes like a prolactinoma; a tumor that compresses the pituitary stalk; or certain medications, such as typical and atypical antipsychotics, antiemetics, or antihypertensives.
Next, polycystic ovarian syndrome or PCOS is thought to be related to insulin resistance, which ultimately seems to result in an elevated LH to FSH ratio, as well as high androgen levels.
PCOS is characterized by anovulation, which results in enlarged ovaries that contain multiple unruptured follicles or cysts, and infertility, as well as an increased risk of endometrial cancer.
Individuals may also present with hirsutism, male-pattern baldness, and acne, as well as obesity, and acanthosis nigricans.
Finally, primary ovarian insufficiency, or premature ovarian failure, is when the ovarian follicles stop functioning in females of reproductive age, resulting in low levels of estrogen and high levels of FSH and LH.
This leads to early menopause before the age of 40. Symptoms include anovulation, amenorrhea, and infertility, as well as early signs of menopause.

Summary35:40–37:01

Now, back to our cases. Ana is a 17 year old female who came in because she hasn’t had her first menstrual period by the age of 15, which is a pretty straightforward case of primary amenorrhea.
The real question here is what’s causing it. Some key findings are her short stature and webbed neck, which combined with her shield chest should make you think of Turner syndrome.
This suspicion is supported by her blood test, which shows low estrogen levels and high FSH and LH levels. Next, comes María, a 25 year old female who hasn’t had her period for nine months, which points to secondary amenorrhea.
Since she’s sexually active, the first thing to rule out is pregnancy, which came up negative. What’s key in this case is that María does strenuous exercise every day, along with a strict diet with severe caloric restriction, which have led María to be underweight.
This is characteristic for anorexia nervosa. The final clue is her blood test, which reveals low levels of estrogen, LH, and FSH.
This confirms that María has functional hypothalamic
Amenorrhea: Pathology Review: Video and Causes | Osmosis