Investors in Mayne Pharma are escalating pressure on the Adelaide-based healthcare group to divest its US women's health and dermatology businesses.

The push for a strategic break-up intensifies after the Australian federal government blocked a takeover bid by private equity firm Cosette last year, leaving shareholders seeking alternative paths to unlock value.

The Australian Financial Review reports that major investors are not ruling out seeking a board spill if the current management team fails to take drastic action.

The threat of a leadership change underscores growing frustration with the company's trajectory following the regulatory rejection of the acquisition.

Mayne Pharma's shares have underperformed in the wake of the blocked deal, prompting calls for structural reform.

The focus on the US women's health and dermatology segments suggests investors view these units as key levers for potential value creation, either through sale or spin-off.