Medoxyprogesterone
[CAS# 520-85-4]

Identification

• Classification: Analytical chemistry >> Analytical reagent >> Ion chromatography reagent
• Name: Medoxyprogesterone
• Synonyms: 6alpha-Methyl-17alpha-hydroxypregn-4-ene-3,20-dione; NSC 27408; U 8840
• Molecular Formula: C₂₂H₃₂O₃
• Molecular Weight: 344.49
• CAS Registry Number: 520-85-4
• EC Number: 208-298-6
• SMILES: C[C@H]1C[C@@H]2[C@H](CC[C@]3([C@H]2CC[C@@]3(C(=O)C)O)C)[C@@]4(C1=CC(=O)CC4)C

Properties

• Density: 1.13±0.1 g/cm³ Calc.^*
• Melting point: 220-223.5 �ºC (Expl.) ^**
• Boiling point: 488.0±45.0 ºC 760 mmHg (Calc.)^*
• Flash point: 263.0±25.2 ºC (Calc.)^*
• Solubility: Practically insoluble water (0.012 g/L) (25 ºC), Calc.^*, DMSO 20 mg/mlL (Expl.)
• Index of refraction: 1.554 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2014 ACD/Labs)

^** Babcock, John C.; Journal of the American Chemical Society 1958, V80, P2904-5.

Safety Data

• Hazard Symbols: GHS08 Warning
• Hazard Statements: H361
• Precautionary Statements: P203-P280-P318-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	2	H361
Carcinogenicity	Carc.	2	H351
Reproductive toxicity	Repr.	1A	H360

Discovory and Applicatios

Medroxyprogesterone is a synthetic progestin, structurally related to the natural hormone progesterone. It is most commonly encountered in its acetate form, medroxyprogesterone acetate (MPA), which has been widely used in clinical medicine for decades. Medroxyprogesterone was developed in the mid-20th century during a period of extensive research into steroid hormones and their synthetic analogs, with the goal of improving oral bioavailability, prolonging biological activity, and enhancing therapeutic specificity.

Medroxyprogesterone acetate was first synthesized in the 1950s and subsequently approved for medical use. It became a significant therapeutic agent in the management of various gynecological and hormonal disorders. Its development was part of broader efforts to create effective hormonal therapies that could be administered orally or via injection, offering longer-lasting effects compared to natural progesterone, which is rapidly metabolized in the body.

One of the primary uses of medroxyprogesterone is in hormonal contraception. As a component of long-acting injectable contraceptives, medroxyprogesterone acetate is administered intramuscularly or subcutaneously to provide effective birth control for approximately three months per dose. It functions by inhibiting ovulation, altering the endometrium, and thickening cervical mucus, all of which contribute to its contraceptive efficacy. The injectable form, marketed under names such as Depo-Provera, became widely used due to its convenience and high effectiveness.

In addition to contraception, medroxyprogesterone is employed in hormone replacement therapy (HRT), particularly in combination with estrogens. In postmenopausal women, the addition of a progestin like medroxyprogesterone to estrogen therapy reduces the risk of endometrial hyperplasia and endometrial cancer associated with unopposed estrogen use. The combined therapy helps alleviate menopausal symptoms such as hot flashes, night sweats, and vaginal dryness while maintaining endometrial health.

Medroxyprogesterone is also used in the treatment of menstrual disorders, including amenorrhea and abnormal uterine bleeding. In these contexts, it helps to restore normal menstrual cycles and regulate hormonal imbalances. Furthermore, it plays a therapeutic role in managing endometriosis, where its progestogenic activity suppresses endometrial proliferation and can alleviate associated pain and bleeding.

Beyond gynecological uses, medroxyprogesterone has applications in oncology. It has been utilized as a palliative treatment for advanced endometrial and renal cancers, and occasionally in breast cancer, due to its antiproliferative effects on hormone-sensitive tissues. The exact mechanisms are complex and involve interactions with progesterone receptors and modulation of hormone-responsive gene expression.

In patients with hormone-sensitive conditions or contraindications to estrogen, medroxyprogesterone may serve as a monotherapy option. Its use in patients with chronic anovulation, polycystic ovary syndrome (PCOS), or estrogen-dominant conditions has been documented in clinical practice.

The pharmacological profile of medroxyprogesterone includes good oral absorption and a long half-life when given intramuscularly, contributing to its sustained action. It binds to progesterone receptors in target tissues, exerting progestational effects similar to those of endogenous progesterone, but with greater potency and duration.

While effective, the use of medroxyprogesterone is associated with potential side effects, including weight gain, headache, mood changes, and decreased bone mineral density with long-term use. In contraceptive use, delayed return to fertility after discontinuation has also been reported. These effects are generally dose-dependent and vary based on the route and duration of administration.

Due to its wide range of therapeutic uses, medroxyprogesterone remains an important medication in reproductive health, endocrinology, and oncology. Its development marked a major advancement in steroid chemistry and hormone therapy, and it continues to be studied and applied in diverse clinical settings around the world.

References

1979. [MAP in the treatment of adenocarcinoma of the endometrium]. Minerva ginecologica.
URL: https://pubmed.ncbi.nlm.nih.gov/460664

2024. Principles of Antithrombotic and Fibrinolytic Therapy. Non-Neoplastic Hematologic Disorders.
DOI: 10.1007/978-3-031-62373-8_39

1969. Parenteral Medroxyprogesterone as a Contraceptive Agent. Public health reports (Washington, D.C.: 1896).
DOI: 10.2307/4593755