oral treatment, endometriosis, adenomyosis, chocolate cyst, ocarian endometriosis, oral drugs, GnRh analogue, elgolix, danazol, progesterone, ectopic endometrium, infertility, pain, laparoscopy, dysmenorhea, analgesic, NSAID antinflamatory

1. ORAL TREATMENT OF
ENDOMETRIOSIS
By
Magdy abdelrahman mohamed
Assist professor of OB/GYN
Sohag university

2. WHY MEDICAL TTT
High rate of recurrence.
Adjunct to surgery.
Complication of surgery
even minimally invasive.
More accepted by patients.
Suitable for patients near
menopause.

3. WHY ORAL MEDICATION
More convenient.
 Avoidance of injection site
reactions.
More economic.
Could be used daily for long time.

4. IDEAL MEDICATIONS
Curative rather than suppressive
Long-term use should be safe and affordable
Non-contraceptive nature
Not teratogenic.
Inhibits the growth of already existing lesions
Aborts the development of new lesions.
Acceptable side effect
Bedaiwy M et al, Fertil Steril 2017

5. TREATMENT OF
ENDOMETRIOSIS
Management of pain.
Medical
Surgical
Management of infertility.
Medical therapy has limited role.
Surgical.
Assisted reproduction.

6. TRADITIONAL ORAL DRUGS
(1ST LINE)
 NSAID.
 COCs ( in continuous manner)
 Oral progestins
 Norethisterone acetate (NETA), Dienogest, Desogestrel, Danazol.
Lazzeri L et al. 2010.

7. OTHER ORAL DRUGS
GnRH antagonist (Elagolix).
Aromatase inhibitors.
SERM.
SPRM.
Cabergoline.
Non hormonal ttt.
Anti-angiogenics, Rapamycin, Pentoxifylline,
Pioglitazone.. Etc.

8. DIENOGEST
Strong progestational effects.
Moderate antigonadotrophic effects
Anti-androgenic.
No glucocorticoid, mineralocorticoid
activity.
Could be used up to 2 years.
Dose 2mg/day…… incomplete
suppression of ovarian function.
Buggio L et al, 2017.

9. GNRH ANTAGONIST
ELAGOLIX
In July 2018, the US FDA approved
elagolix tablets for the treatment of
moderate to severe pain associated with
endometriosis
 Diamond et al., 2014

10. Up to 6 monthUp to 2 yrs
BMDMenstrual
irregularities
No contraindications
High cost
Contraindications
(CVS, DVT & liver)

11. AROMATASE INHIBITORS
Letrozol & anastrozol.
With progestin add-back led to 75% reduction of
endometrioma volume and improved pain symptoms
after 3 months of treatment.
Patients should be counseled about the off-label nature
of its use for endometriosis.
 Agarwal et al., 2015, Almassinokiani et al., 2014.

12. SERM
Raloxifine & Bazedoxifene.
Animal studies were encouraging in
decreasing endometriotic lesion however
in humans the results were disappointing.
Stratton et al., 2008, Lyu et al., 2015, Naqvi et al., 2014.

13. SPRM
Mifeprestone: Most clinically studied SPRM,
alleviation of symptoms & amenorrhea after 6
m of treatment.
Asoprisnil:. Its use stopped since 2005.
Ulipristal acetate: Study in rat showed
edecrease COX-2
Tanaproget: Effective on animal studies.
Kettel LM et al, 1998, Zhang YX, 2016, Chawlisz et al., 2005 & (Hunaidi et al., 2013)

14. CABERGOLINE
Decrease VEGF.
Inhibitory effect on GnRH secretion.
Comparable to GnRH agonist in
reducing endometriotic lesion.
 Novella-Maestre et al., 2009, Ercan et al., 2015.

15. ANTI-ANGIOGENICS
Atorvastatin & Simvastatin.
Decreased VEGF level.
Decreased endometrial implants and
matrix metalloproteinases (MMP-3).
Most of studies in animal & in vitro human
cell culture.
Sharma et al., 2010. Almassinokiani et al., 2013.

16. NON-HORMONAL
IMUNOMODULATERS
Rapamycin (Sirolimus).
Used to Prevent organ transplant
rejection.
Statistically significant decreases
endometriotic lesion surface area.
Ingelmo et al., 2013, Ren et al., 2016.
Pentoxifylline: cochrane review
……There is lack of evidence.
(Lu D et al, 2009)

17. NON-HORMONAL TTT
Rosiglitazone & Pioglitazone.
Statistically significant reduction of
endometriotic lesion compared with placebo in
animal & human cell culture.
Lebovic et al., 2007, Chang et al., 2013.
Valproic acid. Induce the apoptosis of
endometrial stromal cell. Chen Y et al, 2015.
Cannabinoids. Management of pain.
Jerome Bouaziz et al, 2017

18. TAKE HOME MESSAGE
Several regimens were introduced as
treatment of fibroid. The most promising
belong to two categories: SPRM & orally
active GnRH blockers.
Medical treatment could be considered in
women who refuse a surgical approach
or as a first-line treatment in women near
to menopause at least an adjunct to
surgery.

19. TAKE HOME MESSAGE
The oral medical treatments are helpful for
many women with endometriosis ( esp.
Dienogest & elagolix) , the limitations include
side effects and contraceptive actions.
No doubt that the hope of any patient to be
treated by pills instead of surgeries even
minimally invasive one.
New future research about pathogenesis of
endometriosis could permit the development
of ideal drug.