Amenorrhea: Primary

Chapters:

Watch video only

Introduction0:00–0:42

In amenorrhea, menorrhea refers to menstrual bleeding, or simply menstruation. Well, a means the absence of something.
So amenorrhea is the absence of menstruation. Now, physiologic amenorrhea is normal and occurs before puberty, during pregnancy and lactation, and after menopause.
However, there are also pathologic causes of amenorrhea. Primary amenorrhea refers to situations where a person has never had menstruation by 15 years of age, while secondary amenorrhea occurs when a person who used to have regular menstrual cycles stops having menstruation for a while.
The menstrual cycle usually lasts about 28 days, or starts on the first day of menstruation, when the lining of the uterus begins to shed.

Physiology0:42–1:36

The entire process is controlled by the hypothalamic, pituitary ovarian, or HPO axis. Which is a connection between, you're never gonna believe this, the hypothalamus, pituitary gland, and ovaries.
First, the hypothalamus releases gonadotropin-releasing hormone, or GNRH, which travels through the blood vessels of the pituitary stalk to reach the pituitary gland.
Here, GNRH signals the pituitary gland to release follicle stimulating hormone, or FSH and luteinizing hormone, or LH. Next, FSH and LH travel through the bloodstream to the ovaries, where they regulate the release of estrogen and progesterone, which are crucial for maintaining normal menstrual cycles.
Now, primary amenorrhea covers three scenarios. First, it refers to situations where a person hasn't had their first menstruation by 15 years of age, despite normal growth, and the development of secondary sexual characteristics like breasts and pubic hair.

Pathology1:36–2:20

Second, it refers to individuals who haven't had their first menstruation by 13 years of age, and haven't developed secondary sexual characteristics.
Third, it can mean no menstruation within 5 years after breast development begins. The most important causes of primary amenorrhea include Mullerian agenesis, Turner syndrome, androgen insensitivity syndrome, and imperforate hymen.
Let's start with Mullerian agenesis, also known as Meyer-Roatansky Kosterhauser syndrome. During early fetal development, all individuals start the development of a reproductive system with a pair of Mullerian ducts.

Müllerian agenesis2:20–3:56

In biological females, these ducts develop into the uterus, cervix, and the upper 2/3 of the vagina. However, in biological males, the testes release anti-Mullerian hormone, which causes these ducts to shrink and disappear.
In other words, the anti-Mullerian hormone prevents the development of the female reproductive system and promotes the formation of the male reproductive system.
Now, in Mullerian agenesis, Mullerian refers to the Mullerian ducts, and agenesis means the failure to develop. So, in biological females, the Mullerian ducts fail to develop properly, leaving the uterus, cervix, and upper vagina either missing or severely underdeveloped.
And because there's no uterus, the uterine lining can't shed, which results in primary amenorrhea. Also, without a uterus, carrying a pregnancy isn't possible, leading to infertility.
Remember, the ovaries develop independently of the Mullerian ducts, so these individuals have normal production of estrogen and progesterone.
As a result, their hypothalamic pituitary ovarian axis works normally, so they go through puberty and develop secondary sexual characteristics like anyone else.
For diagnosis, order an abdominal ultrasound to identify any structural abnormalities of the reproductive system, since surgical treatment is often necessary to address these issues.
Next up is Turner syndrome. Normally, biological females have 2 X chromosomes and a 46 XX karyotype.

Turner syndrome3:56–5:36

However, in Turner syndrome, they have 45 chromosomes, with only 1 X chromosome present. The second X chromosome could either be partially or completely absent.
Either way, one functioning X chromosome is not enough for normal ovarian development, which accelerates the depletion of ovarian follicles.
By age 2, the ovaries turn into streak gonads, which are fibrous tissue that cannot produce hormones. So even though the hypothalamus is releasing GNRH and the pituitary gland is producing FSH and LH, the ovaries are not releasing estrogen or progesterone.
Without estrogen and progesterone, the menstrual cycle never begins, causing primary amenorrhea and infertility. Also, non-functional ovaries can't trigger puberty, so the body does not develop secondary sexual characteristics.
On top of these challenges, individuals with Turner syndrome typically have short stature. Diagnosis primarily relies on karyotype analysis, which typically reveals the 45 X0 karyotype, or sometimes the 46 XX 45X0 mosaicism.
Also, an abdominal ultrasound might reveal underdeveloped or completely absent ovaries. Finally, treatment involves estrogen replacement therapy to induce puberty and support the development of secondary sexual characteristics, along with growth hormone therapy to promote normal growth.
Now, moving on to androgen insensitivity syndrome. During fetal development in biological males, the testes produce testosterone, which binds to androgen receptors and promotes the normal development of the male reproductive system, including the external genitalia.

Androgen insensitivity5:36–7:05

In androgen insensitivity syndrome, the testes produce plenty of testosterone, but the body can't use it because the androgen receptors don't work.
As a result, the body converts the extra testosterone into estrogen, which disrupts the normal development of male genitalia, making them look more female instead.
Sometimes, it might appear as a mix of both, known as ambiguous genitalia. Meanwhile, the testes carry out their role by releasing the anti-mullerian hormone, preventing the formation of the uterus.
So even though the external genitalia might look female on the outside, there's no uterus, so there are no menstrual cycles, which results in primary amenorrhea.
Diagnosis primarily relies on karyotype testing and imaging. Karyotype testing typically reveals a normal 46 XY pattern, but sometimes it shows 45 X0, 46 XY mosaicism.
Imaging reveals testes hidden in the abdomen or inguinal region, along with the absence of the uterus and ovaries. Finally, treatment involves surgical interventions to handle undescended testes and reduce the risk of testicular cancer, along with counseling to support gender identity.
Finally, let's talk about imperforate hymen. The hymen is a thin membrane at the opening of the vagina, with a small opening in the center.

Imperforate hymen7:05–7:57

When the uterus lining sheds, this hole enables menstrual blood to flow out of the vagina. In the imperforate hymen, there is no opening at all.
Think of it as a dam blocking the river. No water can flow past it.
So even though the hypothalamic pituitary ovarian axis works normally, and the uterus sheds as it should, the blood can't escape because of the sealed hymen, leading to primary amenorrhea.
Diagnosis mainly relies on a physical exam that reveals the missing hymenal opening. The good news is that the treatment involves a simple intervention called hymenectomy, which creates an opening in the hymen, allowing normal blood flow during menstruation.
All right, it's a quick recap. Mullerian agenesis happens when the uterus, cervix, and upper vagina don't develop properly, so there's no uterus to shed its lining.

Review7:57–8:48

Without shedding, menstruation never happens, causing primary amenorrhea. In Turner syndrome, a missing or incomplete X chromosome causes early ovarian failure.
Without working ovaries, there's no estrogen and progesterone, so the menstrual cycle never begins, leading to primary amenorrhea.
Next, in androgen insensitivity syndrome, the body fails to respond to testosterone, which causes external genitalia to look more female, but since there is no uterus, there is no menstruation, which results in primary amenorrhea.
Lastly, in imperforate hymen, the hymen completely blocks the vaginal opening, trapping menstrual blood and preventing its flow.