The Sienese exploited the economic potential of the city, weakening it substantially. Plagues (the most severe in 1348 and 1400) and demographic downturn brought the city to a deep decadence, as well as the insalubriety of the place, since Siena did not perform any reclamation works in the whole Maremma. In 1554, during the war between the Republic of Siena and Duke Cosimo de' Medici, the Massa fortress capitulated, besieged by the Spaniards led by Carlo Gonzaga.