Progestogens are steroid hormones that are synthesized and secreted by the corpus luteum under the influence of LH. Their main function is the preparation of the uterus for implantation and maintenance of pregnancy. They are classified based on their structure and include natural progesterone as well as synthetic derivatives. Common therapeutic uses include oral contraceptives, hormone replacement therapy, dysfunctional uterine bleeding, and endometriosis. Adverse effects may include breast tenderness, headaches, and mood changes. Newer antiprogestins like mifepristone and ulipristal are used for emergency contraception and medical abortion.

1. Progestogens
Prof.C.Adithan

2. Progestrogens
•Synthesis& secretion
•Main Functions
•Classifications and Preparations
•Therapeutic uses
•Adverse effects
•Pharmacokinetics
Anti-progestrogens: Mifepristone, Ulipristal

3. http://anatomy.iupui.edu/courses/histo_D502/D502f04/lecture.f04/Female04/cycle.jpg
 Secreted from CL
 Under the influence
of LH
 Level declines few
days before next
menstrual cycle

4. LH FSH
Progesterone
Oestrogen

5. Cholesterol
Pregnenolone
Progesterone
21-carbon steroid
17-α- Hydroxy
pregnenolone
17- Hydroxy
progesterone
Dehydro-epi
androsterone
Andro-
stenedione Oestrone
Oestriol
TESTOSTERONE OESTRADIOL

6. Main Functions

7. Main function
Preparation of uterus for nidation & maintenance of pregnancy
Uterus:
 Secretary changes (in the oestrogen primed endometrium)
 If ovum is fertilized
 prepare endometrium
 oxytocin & ergonovine actions
 FSH, LH ovulation
 Cervical secretion – thick, viscid, scanty

8. Vagina: induce pregnancy like changes, leucocyte infiltration
of cornified epithelium
Breast: causes proliferation of acini, Act in concert with
estrogen, to prepare breast for lactation
Body temperature: increased (0.50
C)
Respiration: at higher dose stimulate
Pituitary: weak inhibitor of Gn secretion, Negative feedback
primarily at hypothalamus, reduce the frequency of GnRH
pulse
Metabolism: impair glucose tolerance,
19-nortestosterone derivati: LDL and HDL

9. Classifications and
Preparations

10. Classification by Generation
Classificatio
n by
structure
First Second Third
Estranes Ethynodiol
diacetate
— —
Norethindrone
Norethindrone
acetate
Gonanes Norgestrel Levonorgestrel Desogestrel
Gestodene
Norgestimate
Pregnanes Medroxyprogeste
rone acetate
— —

11. Natural progesterone
obtained from soybeans and Mexican yam roots, and
animal ovaries (often).
Progesterone derivatives (C-21 steroid structures)
Hydroxyprogesterone caproate (i.m)
Medroxyprogesterone Acetate (im,Oral)
Megesterol Acetate (oral)
Dydrogesterone (oral)
Almost Pure progestins
Weaker anti-ovulatory action

12. Nomegesterol (oral microionized natural progesterone)
Weak antiandrogenic, Less anti-ovulatory, Strong
antioestrogenic
Micronizing process increase the half-life of progesterone
and reduce its destruction in the GIT and Maxium serum
conc. achieved rapidly
Absorption 2 fold increased when taken with food.
No Adverse effects on mood, lipid profile, glucose
tolerance and pregnancy outcome
Common side effects: Fatigue and Sedation.

13. 19-Nor-testosterone derivative
Older Compounds
 Norethindrone
 Lynestrenol (Ethinyl
oestradiol)
 Allylestrenol,
 Additional weak oestrogenic,
androgenic and anabolic
 potent anti-ovulatory actions
19-Nor-testosterone derivatives: (Gonanes)
Levonorgestrel, Desogestrel, Norgestimate, Gestodene
 All are given orally
 Very potent progestins,
 No androgenic effects, Strong anti-ovulatory actions
 Used in OCS
 Do not antagonize the beneficial effects of estrogens on lipid
profile
 Suitable for women with hyperandrogenemia

14. Synthetic Progestins (Except Gonanes) Vs Natural Progestins
Androgenic effects of synthetic progestins include
fluid retention,
reduction of HDL cholesterol levels,
headaches and
mood disturbance.
Some of 19-nortestosterone are strongly
androgenic
Producing hirsutism and acne

15. Transvaginal Progesterone.
•Most practical non-oral route of
administration.
•Produces uterine effects with minimal
systemic side effects.

16. Clinical Uses

17. • OCS: Minipill, Norplant, conventional OCS
• HRT – to antagonize oestrogen side effects, a progestin lacking
androgenic activity is preferred
• DUB: Adolescent, peri/Menopausal women, Norethindrone 20-40
mg/day promptly stops the bleeding, subsequent cyclic treatment with
estrogen
• Endometriosis: presence of ectopic endometrial cells outside
the uterus, continue to respond to O and P, cause dysmenorrhea, painful
pelvic swelling, infertility.
• Goal of therapy is to induce estrogen poor environment, Continued
admn. of P induces anovulatory, estrogenic poor state by GnRH
• Dysmenorrhea
Clinical uses of Progesterones

18. • Premenstrual syndrome: suppress ovulation (O + P)
• Threatened abortion: only P deficiency cases: pure
P without androgenic and oestrogenic preferred
• Post-partum lactation
• Endometrial cancer: palliative, high dose required
• Hypoventilation
Clinical uses of Progesterones

19. Adverse Effects

20. Adverse effects of Progesterone
• breast engorgement, headache, rise in body
temp, oedema, acne & mood swings
• masculinization of external genitalia in the
foetus
• Increased incidences of congenital
abnormalities
• irregular bleeding or amenorrhea
• lower HDL (19-nortestosterone derivatives)
• hyperglycaemia

21. Pharmacokinetics

22. Pharmacokinetics
•Absorption:
• progesterone undergoes high first pass metabolism.
Therefore synthetic preparations are commonly used.
• Progesterone esters in oily soln. for i.m. admn.
•Metabolism:
• by liver enzymes
• excretion by urine after conjugation

23. Antiprogestins

24. Antiprogestin
Mifepristone
19-norsteroid derivative
Potent anti-progestin
has anti-glucocorticoid and antiandrogen action

25. Mifepristone
Given during
Follicular phase:midcycle surge of Gn from Pituitary
slow follicular development, ovulation
Luteal phase: prevents secretary changes on endometrium

26. Mifepristone
Mechanism:
• Partial agonist, progesterone receptor modulator
• During luteal phase: Block Pregest. PGs Uterine
contraction
• Sensitize myocardium to PGs. Induce menstruation
• HCG production falls, secondary luteolysis, softening of cervix
leading to abortion
ADME:
• F: 25 %, CYP3A4 metabolism, t½: 20 h

27. Uses:
• Termination of early pregnancy – along with
prostaglandin (upto 7 weeks), 600 mg single oral + 400 mg
oral misoprotol or 1mg gemeprost intravaginally
• As a cervical ripening agent: surgical abortion
• Post-coital contraceptive: within 72 hours
• Once a month contraceptive: 200 mg at 2 days after
midcycle of ovulation
• Progesterone sensitive tumors
• Cushing’s syndrome

28. Side effects:
Vomiting, diarrhoea,
pelvic pain or abdominal pain,
about 5% have severe vaginal bleeding
Precaution: Not to be given to a woman with suspected
ectopic pregnancy, hematological disorders, receiving oral
anticoagulants, Liver/renal diseases

29. Ulipristal
• Selective progesterone receptor modulator (SPRM)
• Used in emergency contraceptive (within 5 days, 30 mg)
• Inhibits ovulation by LH surge + direct effect on follicule
• By its action on endometrium, inhibits implantation
• Weaker anti-glucocorticoid activity
• Metabolised by CYP3A4 and drug interaction possible with
rifampicin, phenytoin, carbamazepine
OTHERS:
Onapristone (pure progesterone antagonist) ,
Gestinone (more effective in endometriosis)

30. Thank you