In his second testament (dated 1508), he determined, however, that Anna would be guardian (next to his uncle, Hermann of Cologne, who died in September 1508) and appointed two counselors to assist her.
During this period Anna lived at her Wittum in Gießen with her daughter Elisabeth, while her son Philip remained in Kassel under the supervision of Ludwig von Boyneburg to Lengsfeld.
On this occasion, Anna wanted to introduce her daughter Elisabeth at the Saxon court, as she had been promised at a very early age to John, the eldest son of George the Bearded.
She was never officially recognized as a regent, but she ruled even past 1519, the year her son Philip was declared of age by Emperor Maximilian I.
Anna first married on 20 October 1500 in Kassel the Landgrave William II of Hesse (1469–1509) with whom she had the following children: On 7 September 1519 she married Count Otto of Solms-Laubach (1496–1522), a second marriage: "The historian has to give the landgravine a prominent place in the Hessian history", historian Hans Glagau wrote in 1899.
Landgravine Anna of Hesse, born Duchess of Mecklenburg, would be worthy of a historical-critical biography.
The chaotic conditions in Hesse during the years 1509–1518 were caused by the fact that no legitimate ruler was available, and power had to be exercised by a woman.