Progesterone Assay

Sample

1. This is done on the serum of the patient.
2. Always note the sex of the patient.
3. In the female note the day of the last menstrual cycle.
4. The serum is stable for 7 days at 4 °C.
5. Can store serum for 3 months at -20 °C.

Precautions

1. Avoid hemolysed samples that will affect the result.
2. Take history recent use of radioisotopes because that will affect the result.
3. Estrogen and progesterone therapy will interfere with the result.

Indication

1. This test is part of the infertility study.
   1. Confirm ovulation.
   2. To evaluate the corpus luteum function.
2. To assess high risk for early spontaneous abortion.

Pathophysiology

1. Progesterone is a female sex hormone needed to prepare the uterus for pregnancy.
   1. progesterone is C_²¹  steroids.
   2. The initiation and control of luteal secretion of progesterone are regulated by LH and FSH.
   3. Progesterone has no specific binding plasma protein. This is bound like cortisol to cortisol binding globulin.
      1. Free progesterone is 2 to 10% of the total concentration and this will remain constant throughout the menstrual cycle.
2. This is like estrogen as a sex hormone.
   1. It helps to regulate the accessory organs during the menstrual cycle.
   2. Progesterone acts primarily on the endometrium.
   3. It starts the secretory phase of the endometrium for the preparation for the implantation of a fertilized ovum.
   4. This is important for the implantation of the blastula that is produced by the cleavage of the fertilized ovum.
   5. In nonpregnant females, it is produced by the corpus luteum.
   6. Progesterone maintains the pregnancy.

3. Source of progesterone production:
   1. Progesterone is produced by the Corpus luteum (granulosa cells) of the ovary in the first week of pregnancy.

1. 2. The adrenal cortex and testes are a minor source of progesterone in the male.
      1. The adrenal cortex is a minor source of progesterone in the female as well.
   3. Followed by Placenta during pregnancy which starts producing progesterone.
   4. Placenta produces progesterone by 12 weeks of gestation.

4. The progesterone peak level is a mid-luteal phase of the menstruation.
   1. In non-pregnant women, progesterone is produced by the corpus luteum.
   2. Progesterone in nonpregnant ladies is elevated during the luteal phase, maximal level 5 to 10 days after the LH peak at mid-cycle.

5. Progesterone is metabolized into the metabolites which conjugate with glucuronic acid and excreted as water-soluble glucuronides.
6. The single best test to evaluate ovulation.
   1. A series of the test gives the day of ovulation when there is the peak level of progesterone.
   2. Plasma progesterone level starts to rise with ovulation along with LH hormone approximately 6 to 9 days.
   3. The level falls and menses occur.
7. After ovulation, there is a rise of 4 to 5 days and then it falls.
8. In case of inadequate luteal phase production of progesterone, supplementary progesterone can be given to maintaining early pregnancy.
9. In pregnancy, there is a gradual increase starting from the 9 weeks to 32 weeks of gestation.
10. Its level is higher in the twin pregnancy.
11. Progesterone is converted into Pregnanediol and conjugated with glucuronic acid by the liver and then excreted by the kidneys.
    1. Progesterone 2 to 10% free and rest is bound to corticosteroid-binding globulin (CBG).
    2. Pregnanediol is most easily measured by a metabolite of the progesterone in the urine and plasma.
    3. Pregnanediol level in the urine is unchanged even in the fetal distress or even the death of the fetus.

12. Progesterone and Estradiol (most potent of the estrogen), their role in the secretion of FSH and LH.

NORMAL

Source 1

Age	ng/dL
Cord blood	8000 to 56,000
Premature	84 to 1360
Prepubertal child (1 to 10 years)	7 to 52
Puberty  Tanner stage	Male	Female
1	<10.3 to 33	<10 to 33
2	<10 to 33	<10 to 55
3	<10 to 48	<10 to 450
4	<10 to 108	<10 to 1300
5	21 to 82	10 to 950
Adult	13 to 97	Follicular phase = 15 to 70
		Luteal                   = 200 to 2500
		Pregnancy
		First trimester = 1025 to 4400
		2nd trimester   = 1950 to 8250
		3rd trimester   = 6500 to 22,900

• To convert into SI unit x 0.0318 = nmol/L
• Tanner stage is the physical scale of development of primary and secondary sex characteristics.

Source 2

• Adult  male = 10 to 50 ng/dL
• Adult female:
  • Follicular phase = <50 ng/dL
  • Luteal phase = 300 to 2500 ng/dL
  • Postmenopausal = <40 ng/dL
  • In Pregnancy:
    • First trimester = 725 to 4400 ng/dL
    • Second trimester = 1950 to 8250 ng/dL
    • Third trimester = 6500 to 22,900 ng/dL

Source 4

• Men = < 1.0 ng/mL.
• Women
  • Prepubertal = 0.1 to 0.3 ng/mL.
  • Follicular phase = 0.1 to 0.7 ng/mL.
  • Luteal phase = 2 to 25 ng/mL.
  • Pregnancy:
    • First trimester = 10 to 44 ng/mL.
    • Second trimester = 19.5 to 82.5 ng/mL.
    • Third trimester = 65 to 290 ng/mL.

• There is a lab to lab and method to method variation of the normal values.

Increased progesterone level is seen in:

1. Congenital adrenal hyperplasia.
2. Molar pregnancy.
3. Lipid ovarian tumor.
4. At the time of ovulation.
5. Pregnancy.
6. Choriocarcinoma of the ovary.
7. Theca Lutein cyst of the ovary.

Decreased level of progesterone seen in:

1. Threatened spontaneous abortion.
2. Preeclampsia.
3. Toxemia of pregnancy.
4. Fetal death.
5. Placental failure.
6. Ovarian hypofunction.
7. Amenorrhea.
8. Ovarian cancers.
9. Short luteal phase syndrome.

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