AssessmentsAmenorrhea: Clinical practice
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 29-year-old woman comes to the office due to difficulty conceiving. Menarche was at age 11 years, and her menstrual cycle has been irregular since then. She has been sexually active with her male partner for the past 3 years and has never used any form of contraception. The patient has gained 10kg (22 lbs) weight over the last year and has been unable to lose weight despite changes in her diet. Past medical history is unremarkable. Vitals are within normal limits. Her BMI is 32 kg/m2. Physical examination shows scant thick hair along the jawline and hyperpigmented, velvety plaques under her axilla. Pelvic examination reveals normal external genitalia and a mobile and nontender uterus with no adnexal masses. TSH, LH and prolactin levels are within normal limits. Considering the most likely diagnosis, which of the following is the best approach to manage this patient’s infertility?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Sam Gillespie, BSc
And, finally, the ovarian follicles must secrete estrogen and progesterone in response to FSH and LH stimulation.
In childhood and early adolescence, estrogen leads to the development of secondary sex characteristics - like the development of breasts, and the appearance of axillary and pubic hair.
And eventually, usually 2 to 3 years after the breasts have started developing, the first menstruation, or the menarche, occurs.
So physiology aside, primary amenorrhea is when a female has not begun breast development by age 13 or hasn’t had menarche by age 15.
A pregnancy test is the first step for both primary and secondary amenorrhea, because some females can be pregnant even before they’ve had their first period.
There are five stages. In stage 1, the pre-pubertal stage, no pubic hair is present and females have a flat-chest.
In stage 2, soft pubic hair and breast buds appear.
In stage 3, pubic hair becomes coarser, and breast mounds form.
In stage 4, pubic hair begins to cover the pubic area and breast enlargement continues to form a “mound-on-mound” contour of the breast.
Also, menarche usually occurs during Tanner stage 4.
And finally, in stage 5, pubic hair extends to the inner thigh and the breast takes on an adult contour.
Next, a pelvic ultrasound should be performed to confirm the presence or absence of the uterus, and serum levels of FSH should be drawn.
If there is a uterus, and FSH levels come back high, that suggests gonadal dysgenesis - which is when the gonads didn’t develop properly in utero, and they’re replaced by streak gonads - or functionless, fibrous tissue, which can’t respond to FSH stimulation - hence the high FSH levels.
With Turner’s syndrome, roughly half of the individuals have a 45, X karyotype - meaning they’re missing one of their sex chromosomes. The other half of the individuals have a mosaic of either 45, X and 46, XX or a mosaic of 45, X and 46, XY.
Individuals with Turner syndrome, have a short stature, a wide or webbed neck, a broad chest with widely spaced nipples, low-set ears, as well as arms that turn outward at the elbows.
Turner’s syndrome also has wide ranging medical effects, and requires a full workup of their various organ systems.
Additionally, growth hormone therapy helps with short stature.
This can happen when a fetus has a Y chromosome, which contains the sex-determining region of the Y chromosome - or SRY, but doesn’t have functioning gonads that can make testosterone or mullerian inhibiting factor. Without the influence of these hormones, the fetus develops female internal and external organs and tissues.
Like with Turner’s syndrome, the streak gonads are at high risk of developing cancer, so they should be surgically removed.
Glucocorticoid replacement normalizes blood pressure, but that can sometimes take years - in the meantime, mineralocorticoid receptor blockade with spironolactone can help counter the effects of excess aldosterone precursors.
Ok, now let’s switch gears and see what the differential is for an individual that has a uterus, but their FSH levels come back low.
First step is to repeat the FSH levels and also check LH levels. If both are low, then the most likely cause is a hypothalamic or pituitary disorder, like congenital GnRH deficiency, or constitutional delay of puberty.
Normal adrenarche, however, still occurs, so these individuals do develop pubic hair.
Additionally, in this case, there is also no pubic hair development, because all features of puberty are delayed.
The last clinical scenario is when the ultrasound reveals an anatomic abnormality, like evidence of an outflow tract obstruction, or an absent uterus.
Individuals can have recurring menstrual cramps and pain, without any outwards signs of bleeding.
Both of these can be corrected surgically - an imperforate hymen can be incised close to the hymenal ring, and then built-up blood can be evacuated.
A transverse vaginal septum can be surgically excised.
Alternatively, the ultrasound might show an absent uterus.
The three main causes of this are mullerian agenesis, complete androgen insensitivity syndrome, and 5-alpha reductase deficiency. To tell these three apart, we’ll need a karyotype and serum testosterone levels.