Medroxy­progesterone Acetate

PubChem CID

6279

ECHA InfoCard

• 100.000.689
• EC / List #: 200-757-9

IUPHAR/BPS

2879

DrugBank Accession Number

DB00603

UNII

C2QI4IOI2G

KEGG Entry Number

C08150

Wikipedia Entry Name

Medroxyprogesterone Acetate

ChEBI ID

CHEBI:6716

ChEMBL ID

CHEMBL717

ChemSpider ID

6043

NIST

Medroxyprogesterone Acetate

ATC Code(s)

• G03AC06
• G03DA02
• L02AB02

Appearance

White or almost white crystalline powder, odorless.

Melting Point

PubChem: 214.5° C
IARC: 207-209 °C

Solubility

Practically insoluble in water. Slightly soluble in diethyl ether. Freely soluble in chloroform and dichloromethane. Soluble in acetone and dioxane. Sparingly soluble in ethanol and methanol.

logP

3.5

Specific Optical Rotation

+47 to +53 (dried substance 0.250 g in acetone diluted to 25 mL).
+45 to +51 deg, 10 mg per mL in dioxane.
+61° in chloroform

Storage Conditions

"Preserve in tight, light-resistant containers. Store at 25° C, excursions permitted between 15° C and 30° C."

GHS Hazard Code(s)

Side Effects

Increases risk of breast cancer and coronary heart disease in hormone replacement therapy (HRT) users by disturbing normal signaling of natural androgens which play a protective role against breast cancer. Negative effects on bone density due to glucocorticoid activity. Possible weight gain, increased blood pressure, and cardiovascular complications due to no or very weak antimineralocorticoid activity. As an injectable contraceptive, associated with increased HIV acquisition. Nervousness, abdominal distress, headache, metrorrhagia, amenorrhoea, libido decreased, dizziness, weight increased, asthenia, injection site reaction.

Carcinogenicity

There is sufficient evidence in experimental animals for carcinogenicity of MPA.

Mutagenicity

Non-mutagenic in Ames test, DNA damage/alkaline elution assay, and micronucleus test.

LD₅₀

LD₅₀ dog oral: > 5 g/kg
LD₅₀ mouse intraperitoneal: > 1.5 g/kg
LD₅₀ mouse oral: > 16 g/kg
LD₅₀ mouse subcutaneous: > 1.5 g/kg
LD₅₀ mouse intravenous, single dose: 376 mg/kg
LD₅₀ rat intraperitoneal: > 0.9 g/kg
LD₅₀ rat oral: > 6.4 g/kg
LD₅₀ rat subcutaneous: > 0.9 g/kg
LD₅₀rat intravenous, single dose: ~100 mg/kg

TD_Lo

human women intravenous: 10-21 mg/kg

Androgen Receptor Activity

Reported as weakly effective to effective agonist.

Estrogen Receptor Activity

Antagonist

Glucocorticoid Receptor Activity

No activity

Mineralocorticoid Receptor Activity

No activity

Bioavailability

Near 100%

Elimination Half-Life (t_1/2)

32-44 h (oral administration)

Serum Protein Binding

88% bound to serum albumin, no binding to SHBG or CBG

Metabolism

CYP3A4. No hepatic first pass effects after oral intake.

Excretion

Most metabolites excreted in the urine as glucuronide conjugates with only minor amounts excreted as sulfates. Detectable amounts have been found in milk.

T_max

2-4 h

Enzyme Interactions

• Competitive inhibitor of 3β-hydroxysteroid dehydrogenase/Δ^5-4 isomerase II (3β-HSDII), which is essential for the biosynthesis of sex steroids and corticosteroids.
• CYP3A4: substrate, inducer
• CYP2C8, CYP2C9: inhibitor

Indications

Used as a contraceptive and to treat secondary amenorrhea, abnormal uterine bleeding, pain associated with endometriosis, endometrial and renal cell carcinomas, paraphilia in males, GnRH-dependent forms of precocious puberty, as well as to prevent endometrial changes associated with estrogens.