Megestrol Acetate

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Cat Number

API595335

CAS Number

595-33-5

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CAS Number

595-33-5

EINECS

209-864-5

Storage

Store at room temperature

Synonyms

Megestryl acetate; Megace; Niagestin; Megace ES; Megeron; Ovaban; Ovarid; Megestat

Molecular Formula

C24H32O4

Molecular Weight

384.5

Smiles

CC1=C[C@@H]2[C@H](CC[C@]3([C@H]2CC[C@@]3(C(=O)C)OC(=O)C)C)[C@@]4(C1=CC(=O)CC4)C

Appearance

White crystalline powder

Melting Point

214°C

Boiling Point

507.1°C at 760 mmHg

Relative Density

1.15

General Description

Megestrol acetate is a synthetic progestin derived from 17‑hydroxyprogesterone, featuring an acetoxy group at the 17‑alpha position and a methyl group at the 6‑alpha position. The molecule is a derivative of medroxyprogesterone acetate with an additional 6‑methyl group and a double bond between carbons 6 and 7. These structural features confer potent progestational activity and anti‑gonadotropic effects.

Mechanism of Action

Megestrol acetate binds to progesterone receptors in hormone‑sensitive tissues, inhibiting the release of luteinizing hormone (LH) and follicle‑stimulating hormone (FSH) from the pituitary via negative feedback. It also has direct glucocorticoid‑like activity, which contributes to its appetite‑stimulating effects and may cause adrenal suppression. The drug exhibits moderate anti‑androgenic activity and can inhibit the growth of endometrial and breast cancer cells.

Application

Megestrol acetate is indicated as a second‑line hormonal therapy for advanced breast cancer and endometrial cancer (palliative treatment). It is also approved for the treatment of anorexia, cachexia, or unexplained significant weight loss in patients with AIDS. The appetite‑stimulating effect is dose‑dependent and may be related to its corticosteroid activity.

In rats bearing the Yoshida AH‑130 ascites hepatoma, daily megestrol acetate (100 mg/kg) significantly attenuated loss of body weight, lean mass, and fat mass, and protected against cardiac atrophy. It improved left ventricular function (ejection fraction, fractional shortening) and reduced mortality (hazard ratio 0.44). Mechanistically, megestrol acetate downregulated autophagic markers (Beclin‑1, p62, TRAF6, LC3) in both gastrocnemius and heart. The authors conclude that megestrol acetate improves survival and cardiac function in cancer cachexia by suppressing autophagy.

Fig. 1 Effect of megestrol acetate treatment on body weight and body composition of the tumour‐bearing rats. (Musolino V, et al., 2016)

References

Musolino V, et al. Megestrol acetate improves cardiac function in a model of cancer cachexia-induced cardiomyopathy by autophagic modulation. J Cachexia Sarcopenia Muscle. 2016;7(5):555-566.

A randomized crossover pharmacokinetic study in 93 healthy subjects compared a nanocrystal formulation of megestrol acetate with Megace oral suspension (OS). In the fed state, exposures were comparable. In the fasting state, the nanocrystal formulation achieved 6.7‑fold higher peak concentration and 1.9‑fold higher AUC than Megace OS. No serious adverse events occurred. The nanocrystal formulation is less affected by food intake, making it potentially more effective in cachexia or anorexia patients.

Fig. 2 Study design and treatments. (Jang K, et al., 2014)

References

Jang K, et al. Novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state. Drug Des Devel Ther. 2014;8:851-858.

Does Megestrol Acetate require protection from light during long-term storage?

Yes, it is photosensitive. Light exposure can cause photodegradation and discoloration. Store in light-resistant containers, preferably amber glass.

What is the recommended storage temperature for Megestrol Acetate?

Store at controlled room temperature (15-25°C). Avoid excessive heat above 30°C, which can accelerate hydrolysis of the acetate ester.

Is Megestrol Acetate stable in oral suspension formulations?

Yes, when formulated with preservatives and protected from light.

How is the impurity megestrol (free alcohol) monitored during stability?

This primary hydrolysis product is specifically quantified using a stability-indicating HPLC method, ensuring it remains below USP/EP limits.