Endometriosis Management

Dr R M Maboa
BSc. MBCHB. DOMH
(Diploma in Occupational Health & Medicine)
25 February 2020
MBCHB IV

Sefako Makgatho Health Science University

Department of Pharmacology and Therapeutics

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 Endometriosis
• a condition resulting from the appearance of
endometrial tissue outside the uterus and causing
pelvic pain, especially associated with menstruation.

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 Treatment Algorithm for Endometriosis
Chronic pelvic pain and endometriosis in young women

Functional disorder
• IBS Dietary changes, GI referral
• Pelvic floor myalgia Physical therapy, trigger points
• Depression Psychological evaluation

ENDOMETRIOSIS

Chronic pelvic pain

• Detailed history
• Examination
• Imaging Medical management Conservative surgery
presumptive diagnosis Surgical diagnosis
NSAIDs
Alternative diagnoses OCs
• Adnexal cyst GnRH agonists + add-back
Surgical therapy Other diagnosis
• Chronic appendicitis
• IBD Progestins
Danazol

Solnik J. Curr Opin Obstet Gynecol 2006; 18: 511–518 .

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 Medical Treatment
• Non Steroidal Inflammatory Drugs (NSAIDS)
• Progestogens:
• Dienogest
• Dydrogesterone
• Medroxyprogesterone acetate
• Norethisterone(Primolut N)
• Mixed: Combined oral contraceptives
• Dienogest/oestrogen(Qlaira)
• Cyproterone/oestrogen(Diane-35)
• Drospirenone/oestrogen(YAZ/Yasmin)
• Gestodene/oestrogen(Minesse)
• Levonogestrel/oestrogen(Nordette)
• Norgestrel/oestrogen(Ovral)
• Estrogen-progestin contraceptives
• Alternate progestin treatment options —
• Ethylnorgestrienone (ie, gestrinone
• Etonogestrel implant
• Levonorgestrel intrauterine device

• Gonadotropin-releasing hormone (GnRH) agonists

• Danazol
• Neuropathic pain treatments

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 Danazol(Antigonadotropins)
Indication Dose Pharmacokinetics Adverse Effects MOA
Induces endometrial T1/2=15 hours Acne,greasy skin Danazol competes
atrophy Signs of virilization with androgen and
progesterone at the
receptor level, causing
amenorrhea in 4-6
weeks. Androgenic
effects cause acne,
decreasing breast size
Endometriosis Concentrated in the Cholestatic jaundice
liver, adrenals, kidneys
Benign breast Excretion: faeces and
disorders(gynaecomas urine
tia)
Pre-pubertal breast
hypertrophy
Hereditary angio-
oedema
Cyclical breast pain 100mg bd max.3
and nodularity months

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 Classification of Progestogens
Progesterone Retroprogesterone

Progesterone Dydrogesterone

Progesterone Derivatives Testosterone Derivatives

17-OH-progesterone Derivates 19-progesterone 19-nortestosterone Derivatives
Derivatives

Pregnane Nor-Pregnane Estranes Gonanes

•Hydroxyprogesterone •Nomegestrole acetate •Lynestrenol •Norgestrel
caproate •Demegestone •Levonorgestrel •Desogestrel
•Hydroxyprogesterone •Promegestone •Norethisterone •Gestodene
heptanoate •Nestorone •Norethisterone acetate •Norgestimate
•Gestonorone caproate •Trimegestone •Ethinodiol aiacetate
•Chlormadinone acetate •Norgestrienone
•Medrogestone •Dienogest
•Medroxyprogesterone acetate
•Cyproterone acetate
Spirolactone
Derivative

Drospirenone

Adapted from: Druckmann R. Journal Für Menopause. 2002;1–5.

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3
 Dydrogesterone
Dydrogesterone is a retroprogesterone – a steroisomer of
progesterone – with an additional double-bond between carbon 6
CH3
&7
C O
CH3 CH3

CH3 C O CH3

CH3 H
O
H
O

Kuhl2006

4
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 Progestogens have different hormonal activities

Dydrogesterone Progesterone Medroxy Medrogestone Norethisterone Levonorgestrel

progesterone
acetate

Progestogenic + + + + + +
Oestrogenic – – – – + –
Androgenic – – (+) – + +
Glucocorticoid ? + + ? – –
Anti- androgenic – (+) – – – –

Anti- oestrogenic + + + + + +

Anti- (+) + – – – –
mineralocorticoid
+ = effect – = no ? = unknown (+) = weak
effect effect

Kuhl2005

5
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 Dydrogesterone

∗ First marketed in 19611

∗ The only retroprogesterone commercially available1
∗ Molecular structure closely related to natural
progesterone
∗ Orally active at lower doses than micronised
progesterone2
∗ No oestrogenic, androgenic or glucocorticoid effects

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 DYDROGESTERONE

∗ Compared with oral micronised progesterone

– Has a more rigid structure (positively influences

selectivity)
– Better oral bioavailability
– Requires a 10 – 20 times lower oral dose
– Has good receptor binding selectivity
– Has metabolites with progestogenic activity

Schindler 2009

7
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 Dydrogesterone: Safety and Tolerability
Possible undesirable effects
Common (≥1/100, Uncommon Rare
<1/10) (≥ 1/1,000, < 1/100) (≥ 1/10,000, <1/1,000)
Migraines/headache Depressed mood Increase in size of progestogen
dependent neoplasms
Nausea Dizziness Hemolytic anemia
Menstrual disorders (e.g. Vomiting Hypersensitivity
metrorrhagia, menorrhagia,
oligo-
/amenorrhea, dysmenorrhea
and irregular menstruation)

Breast pain/tenderness Weight increase Somnolence

Abnormal hepatic function (with Angioedema
jaundice, asthenia or malaise, and Breast swelling
abdominal pain)
Allergic dermatitis (e.g. rash, pruritus, Edema
urticaria)

Dydrogesterone SmPC. 29 April 2011.

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 Safety and Tolerability
Interaction with other medications

∗In vitro data indicate that dydrogesterone and its

main metabolite 20 α –dihydrodydrogesterone
(DHD) may be metabolized by cytochromes P 450

∗Metabolism may be increased by concomitant use

of substances known to induce these isoenzymes
such as anticonvulsants (e.g., phenobarbital,
phenytoin, carbamazepine), anti-infectives (e.g.
rifampicin, rifabutin, nevirapine, efavirenz) and
herbal preparations containing e.g. St John’s Wort
(Hypericum perforatum), valerian root, sage, or
gingko biloba
.
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 Safety and Tolerability

∗ Ritonavir and nelfinavir, although known as strong

cytochrome enzyme inhibitors, by contrast exhibit
enzyme-inducing properties when used
concomitantly with steroid hormones

∗ Increased metabolism may lead to a decreased effect

∗ In vitro studies have shown that dydrogesterone

does not inhibit or induce CYP drug
metabolizing enzymes at clinically relevant
concentrations

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 INDICATIONS FOR USE

 Dysmenorrhoea Threatened
 abortion Recurrent abortion
 Luteal phase support in IVF
 Menstrual irregularities
 Secondary Amenorrhoea
 Dysfunctional uterine bleeding
 Endometriosis
 Menopausal hormonal therapy


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