During the clinical examination and treatment of patients with infertility, physicians often request a serum sex hormone panel. This test is used to study and determine the function of the hypothalamic-pituitary-gonadal axis by measuring changes in the levels of various sex hormones in the serum and in conjunction with the observed clinical manifestations. It is of clinical importance and reference value for predicting the time of ovulation, for testing the effectiveness of endocrine therapy, and for diagnosing and differentiating the causes of infertility.
Physiologically, follicle stimulating hormone (FSH) is released by the pituitary gland at the beginning of menstruation, and FSH acts to stimulate the growth of approximately 20 follicles on the surface of the ovary, each containing one egg. Over the next two weeks, the follicles grow while the ovaries secrete another important hormone, estrogen. Estrogen enters the bloodstream and sends negative feedback signals to the brain. If the concentration of estrogen in the blood is high, it inhibits the release of FSH, so that only one follicle receives enough FSH stimulation to grow into a mature follicle.
This is the reason why most pregnancies result in only one child. Elevated estrogen levels in turn stimulate the pituitary gland to release luteinizing hormone (LH), which in turn causes the release of mature eggs from the follicles, which is called ovulation. Ovulation monitoring is not only to determine the presence or absence of ovulation or the day of ovulation, but also to predict the onset of ovulation within 1 to 2 days, or even hours, before ovulation. Therefore, the monitoring methods include ultrasound, sex hormone measurement, cervical scoring and basal body temperature (BBT) measurement. Various ovulation indicators or parameters have different meanings in ovulation monitoring as the cycle changes, and only the significance of sex hormone measurement in ovulation monitoring is discussed below.
Timing of the test
In general, sex hormone testing is performed at different stages of the menstrual cycle, which can be divided into: follicular phase, ovulation phase, and luteal phase. Depending on clinical needs, the doctor may ask the patient to have the test done at a specific time in order to understand the specific endocrine situation in the body: 1.
1. Follicular phase test.
This is the measurement of sex hormones in the serum during the second to third day of the menstrual cycle, in order to understand the basal state of the ovaries. The test consists of all six items, which are indispensable. This is because each sex hormone can reflect different conditions. If the follicle stimulating hormone (FSH) is too high, it means the reserve function of ovary is poor, so the hormone receptors in the ovary can be protected by medication to increase the ovarian reserve; if the estradiol (E2) is too high, the patient may have residual follicles, suggesting that ovulation treatment is not suitable; if the luteinizing hormone (LH) is too high, it will affect the quality of follicles, the follicle fertility will decrease and the miscarriage rate will increase, so the LH treatment can be lowered first. If prolactin (PRL) is too high, it will also affect ovulation and luteal function.
If testosterone (T) is too high, it can affect follicular development, causing numerous small follicles to develop competitively or not at all. If FSH, LH and E2 are too low, hypothalamic-pituitary hypofunction may be the cause and gonadotropin replacement therapy may be considered.
2. Ovulation test.
This is the measurement of sex hormones on the 16th to 17th day of the menstrual cycle, combined with B-ultrasound, to understand the developmental status of the follicles. During this period, only FSH, LH, E2 and P can be measured to be meaningful. When E2 is normal, follicle size is normal, LH has a peak, and P is not high, the conditions are ideal for ovulation, which is expected to occur 24-36 hours after the peak of LH. Abnormal hormone secretion during this period can lead to impaired follicular development and ovulation. If the E2 is low and the follicle is greater than or equal to 1.8 cm on ultrasound, the follicle may be immature or empty; if the E2 is normal and the follicle is less than or equal to 1.6 cm, ovulation may have just occurred or there may be multiple small follicles developing, and there may be missed follicles; if the E2 is normal and the follicle is greater than or equal to 1.8 cm and there is no LH peak, this indicates a disruption of the positive feedback mechanism of the gonadal axis or an immature follicle; if the E2 is too high, this may also predict impaired ovulation. If E2 is too high, it can also predict the occurrence of ovarian hyperstimulation syndrome (OHSS); if the follicle is less than or equal to 1.4 cm, LH or P is already elevated, suggesting premature luteinization of the follicle; if P is greater than 2ug/L, suggesting closure of the uterine implantation window and decreased chance of blastocyst implantation.
3. Luteal phase detection.
On day 21-22 of the menstrual cycle, E2 and P are measured to understand the luteal function, usually 6-7 days after ovulation. If the P value is too low (<10ug/L) during the peak luteal phase, it indicates anovulation or anovulatory luteinization; if the P value is between 10 and 15ug/L, it indicates luteal insufficiency or follicular non-rupture luteinization; if the P value is greater than 15ug/L, it indicates normal luteal function. However, low E2 is also a sign of luteal insufficiency and requires symptomatic treatment. Luteinizing insufficiency is also sometimes a quality problem of the follicle and should be treated mainly before ovulation.
Clinical significance of the six hormones
1. Estradiol (E2).
E2 is the most active of the estrogens and is mainly produced from the follicles of the ovaries and the placenta, with small amounts produced from the adrenal glands and testes. Serum E2 measurement is a very useful indicator for the evaluation of various menstrual abnormalities: early or delayed puberty in girls, primary or secondary amenorrhea, premature ovarian failure, etc. In patients with infertility, monitoring of serum E2 is useful for monitoring ovulation induction and subsequent treatment, such as with clomiphene, LH-releasing hormone (LHRH) or exogenous gonadotropins. In in vitro fertilization (IVF), the use of chorionic gonadotropin (HCG) and the collection of oocytes are usually optimally adjusted daily when the ovaries are hyperstimulated, and serum E2 concentrations are also measured.
2. Progesterone (P).
In women, it is mainly produced by the ovaries and the placenta. The main function of progesterone is to promote endometrial thickening and glandular hyperplasia in preparation for implantation of the fertilized egg. The activity of ovarian follicles and the corpus luteum can be inferred from the rise and fall of progesterone concentration. Therefore, progesterone measurement in blood is used clinically to monitor ovulation and normal function of the corpus luteum in non-pregnant women, progesterone therapy monitoring and evaluation of early pregnancy, etc. It is particularly important in determining the functional status of the corpus luteum. It is particularly important in determining the functional status of the corpus luteum. It can help to find the cause in women who are not pregnant and in women with recurrent spontaneous abortions.
Elevated serum progesterone: seen in gravida, mild gestational hypertension syndrome, diabetic pregnancies, multiple births, secondary hypertension, congenital 17-a hydroxylase deficiency, congenital adrenal hyperplasia, ovarian granulosa laminaris cell tumor, ovarian lipoid tumor.
Decreased progesterone: seen in pre-eclampsia, luteal dysfunction, fetal growth retardation, stillbirth, and severe gestational hypertension syndrome.
On the 18th to 26th day of the menstrual cycle, if the blood P is measured three times, if it is less than 15.9 nmol/L (5ng/ml), it can be diagnosed as luteal insufficiency.
3.Testosterone (T).
T is the most important androgen in human body. In women, it mainly comes from the adrenal cortex, and the ovaries can also secrete a small amount. High levels of testosterone in women are generally seen in hirsutism, masculinization, polycystic ovary syndrome, ovarian tumors, adrenal tumors and adrenal hyperplasia.
4. Prolactin (PRL).
RL is mainly used in the body to initiate lactation and make the fully matured breast lobules to lactate into the glandular cavity. It has a certain role in the development of the mammary gland. It acts synergistically with estrogen, progesterone and glucocorticoids in mid-pregnancy. It has a role in the synthesis of ovarian hormones, luteal production and lysis. It has an important role in the development and growth of the fetus, especially in the formation of the fetal lung. The secretion of PRL is controlled by the hypothalamus.
Normal breastfeeding and mechanical stimulation of the breast can also lead to the release of PRL, and physical and emotional stress, hypoglycemia, and sleep can also cause an increase in PRL, which can suppress gonadal function and is therefore an important indicator of infertility.
In women of childbearing age, an increase in serum PRL can cause “nonproductive” breast overflow, amenorrhea and menstrual disorders; high RL can be caused by hypothyroidism, pituitary or hypothalamic tumors, renal failure, surgery, use of certain drugs (estrogen, reserpine, methyldopa, tranquilizer, phenothiazine, etc.), sexual intercourse, etc.; low RL can be caused by hypopituitarism, Sheehan’s syndrome, and use of certain drugs (bromocriptine). The causes of low RL are: hypopituitarism, Sheehan’s syndrome, use of certain drugs (bromocriptine, dopamine, etc.). In postmenopausal women, PRL decreases and is lower than in women with normal menstrual cycles.
5. Follicle stimulating hormone (FSH).
FSH is secreted by basophilic cells of the anterior pituitary gland and is controlled by luteinizing hormone-releasing factor (LHRH) produced by the hypothalamus. During the menstrual period in women of childbearing age, blood levels of FSH vary with the levels of estradiol and luteinizing hormone. The increase in FSH is also seen in primary ovarian failure, women in late menopause and after gonadectomy.
A decrease in FSH indicates abnormalities in the hypothalamic pituitary axis, which can be seen in amenorrhea due to pituitary dysfunction, Sheehan’s syndrome, polycystic ovary syndrome, adrenal tumors, and ovarian tumors.
The concentration of follicle stimulating hormone (FSH) in the blood measured on day 3 of menstruation can be used to predict the ability to conceive. If FSH is higher than 15 mIU/mL, it indicates poor fertility, and if it is higher than 40 mIU/mL, it represents ovarian failure in clinical practice.
6. Luteinizing hormone (LH).
LH secretion is controlled by hypothalamic luteinizing hormone releasing hormone (LHRH) and varies with the level of estrogen and progesterone in the serum. In postmenopausal women, LH secretion is increased due to a decrease in estrogen secretion as a result of reduced ovarian function, which relieves the negative feedback to the hypothalamus. Clinical elevation of LH is commonly seen in premature ovarian failure, menopausal syndrome, pituitary or hypothalamic tumors, ovarian insufficiency, Turner syndrome, polycystic ovary syndrome, and decreased LH levels, which can cause infertility, in pituitary dysfunction, Sheehan syndrome, pituitary resection, obesity genital degeneration syndrome, anorexia nervosa, and after estrogen use.
FSH and LH are both produced by the anterior pituitary gland and are secreted in a pulsatile manner during the menstrual cycle with significant temporal differences. In women, FSH promotes follicular maturation and is an important item in the diagnosis of infertility. LH and FSH are “synchronized” during the menstrual cycle and are often measured simultaneously.
If FSH and LH levels are low, the pituitary gland is underactive. If FSH and LH are normal or elevated, the pituitary gland is not the problem but the ovaries themselves, and there is a possibility of premature failure. In this case, it is still necessary to continue to adhere to manual cycle therapy to maintain ovarian and uterine function.
Hypergonadotropic evidence.
FSH > 40 IU/L (40 miu/ml)
LH > 25 IU/L (25 MIU/ml)
E2 < 110 pmol/L (30 pg/ml)
If seen in women under 40 years of age, premature ovarian failure or ovarian insensitivity syndrome should be considered. If FSH is exceptionally high, the patient may be considered infertile. If LH is also high, the diagnosis of ovarian failure can be established.