Progesterone in Pregnancy
Progesterone in Pregnancy
Progesterone in Pregnancy
pregnancy
Dr Karuna SR MRH
• Introduction
• Role in menstrual cycle
• Action
• Classification
• Role in RPL
• Role in preterm birth
• Role in infertility management
• Role in medical abortion
• Role in contraception
Introduction
• Discovery and isolation- Professor Willard Allen and Professor
George Corners
• In Embryology laboratory
• As a substance in the corpus lutuem that sustained pregnancy
• Secreted primarily by
• Ovaries in females
• Testes in males
• Adrenal glands
• Brain and glial cells
• Precursor to hormones
• Estrogen
• Testosterone
• Adrenal hormones - cortisol and aldosterone
• No role in secondary sexual characteristics development at
puberty
• No great quantitative differences between men and women (at
least outside the luteal phase)
• Essential to maintain pregnancy
Chemistry
• C21H30O2 (Carbon 21, Hydrogen 30, Oxygen 2)
• Molecular weight 314.46g
• Derived from cholesterol.
• Hydrophobic
• Bioavailability - prolonged absorption
• Protein binding - 96%-99%
• Metabolism- hepatic to pregnanediols and pregnanolones
• Excretion renal
Levels of progesterone in the menstrual
cycle
Action of progesterone
• Progesterone’s physiological effects- amplified in the presence
of estrogen.
• increases the core temperature during ovulation
• Anti-inflammatory agent
• Converts endometrium to secretory stage for implantation.
• Prevents contractions of the uterus- maintain pregnancy
• Make cervical mucus- thick and impenetrable to sperms
• Reduces spasm and relaxes smooth muscle
• Reduces gall-bladder activity
• Contribute to development of thrombosis in the predisposed
• alveolobular development of the breast secretory apparatus
• prevent ovulation and reduce menstrual bleeding
• decreases SHBG and is responsible for acne and hirsutism
• Fat metabolism –
• Promotes fat deposition
• Decreases HDL
• Increases triglycerides
• No effect on LDL
• Carbohydrate metabolism –
• increases basal insulin levels
• increases insulin response to glucose,
• promotes glycogen storage (liver) and
• promotes ketogenesis
• Protein metabolism – no significant effect
Classification of progesterone
Generations of progestins :
Comparison
LNG 16 hrs
Gestodene 12-18hrs
Desogestrel 12 hrs
Norethindrone 8hrs
Natural progesterones
• Well tolerated.
• Safe in pregnancy.
• Available in all routes of administration
• Improved bioavailability
• Typical ‘progesterone’ side effects of bloating, breast
tenderness, mood changes etc. Are less.
• No change in coagulation process or blood pressure
• Types and brand available
Micronized progesterone
• Natural progesterone
• Decreasing particle size increases absorption & bioavailability
• Dose dependent increase achieved
• To fully protect endometrium- 300mg/day in divided doses is
required.
• Maximum absorption after food than on empty stomach
• Short acting- needs multiple doses
• Lipid friendly
• Suitable for treatment of LPD, DUB, HRT, premenstrual syndrome and
for progesterone challenge test
Safety of progesterone
Side effects:
• Injectable progestogens- injection site reactions and urticaria
• Vaginal progesterone gel- vaginal discharge in 8-9%
• Other- sleepiness, fatigue, headaches and gastrointestinal
disturbances are more with oral preparations than with vaginal
and oral sustained release preparations
Risk of congenital malformations
• No virilisation of female fetus has been found
• Only concern- possible increased risk of hypospadias in male
offspring exposed to exogenous progestins, even if real, however,
this risk is limited to exposure prior to 11 weeks of gestation
Progesterone and preterm birth
March 2012
1. Singleton gestations, no prior PTB and short CL 20mm at 24 weeks- vaginal
progesterone, (90-mg gel or 200-mg suppository)- reduction in PTB and perinatal
morbidity and mortality
2. Universal CL screening of singleton gestations without prior PTB for prevention of
PTB -object of debate
3. Singleton gestations with prior PTB 20-36 6/7 weeks, 17-alpha-hydroxy-
progesterone caproate 250 mg intramuscularly weekly, preferably starting at 16-20
weeks until 36 weeks, is recommended.
4. Not associated with prevention of PTB in women who have in the current
pregnancy multiple gestations, preterm labor, or preterm premature rupture of
• Double blind randomized placebo controlled trial
• Involved 1228 women with singleton pregnancies at risk for preterm birth
because of a positive fetal fibronectin test, a history of spontaneous
preterm birth at 34 weeks of gestation or earlier, or a cervical length 25 mm
or less.
• randomized to use vaginal progesterone 200 mg daily from 22 to 24 weeks
through to 34 weeks of gestation or placebo.
• Progesterone had no significant effect on either the obstetric or childhood
2016
OPPTIMUM studied 1197 women
1. Inclusion criteria- broad
2. Randomised at 22–24 weeks of gestation
3. Trial has been broadly described as a negative one.
4. No significant reduction in the composite primary outcomes was
identified
5. Vaginal progesterone associated with a significant reduction in
neonatal death (odds ratio OR 0.17; 95% confidence interval, 0.49)
95% ci 0. And Neo brain injury (OR 0.50; 95% 0.84). Ci 0.
VAGINAL PROGESTERONE IS AS EFFECTIVE
AS CERVICAL CERCLAGE TO PREVENT PRETERM
BIRTH IN WOMEN WITH A SINGLETON
GESTATION, PREVIOUS SPONTANEOUS
PRETERM BIRTH AND A SHORT CERVIX:
UPDATED INDIRECT COMPARISON META-
24 March 2018
ANALYSIS