BERLIN (AP) _ The mayor of Leipzig resigned today after his city was hit by the largest pro-democracy demonstrations in East German history, the state-run news agency ADN reported.

Bernd Seidel, 40, stepped down because he had lost the confidence of Leipzig citizens, ADN said.

About 300,000 people demonstrated for reforms in Leipzig on Monday, and a similar number took to the streets of the city of 650,000 last week.

The pro-reform demonstrations began in Leipzig two months ago, about the same time thousands of East Germans began fleeing to the West. The protests spread across the country, which was rocked by protests again Thursday.

Also today, a senior health official said the exodus of thousands of skilled workers is seriously straining medical services in East Germany.

East Germany's state-controlled media also reported widening calls for the resignations of top Communist Party leaders. A West German newspaper reported that the East German premier, Willi Stoph, will step down next week.

The mass-circulation Bild newspaper, which forecast the ouster of East German leader Erich Honecker last month, reported today that Stoph will be removed at a party Central Committee meeting convening Wednesday.

About 70,000 East Germans have fled the country since August, citing dissatisfaction with the authoritarian government.

Dr. Geerd Dellas, the health administrator for the city of East Berlin, told a Communist newspaper that 1,100 doctors and nurses had left East Berlin so far.

''The situation is so difficult that an emergency system of aid is going on,'' Dellas told the newspaper Berliner Zeitung.

''The (East) Berlin health and social services have been seriously strained by the departure of doctors, dentists, scientists and other medical personnel,'' Dellas said.

He said doctors and nurses from exclusive clinics serving high-ranking Communist officials have been drafted to work in ordinary hospitals. Nurses still in school who were near graduation have also been employed, Dellas said.

The West German ZDF television network reported that Dresden mayor Wolfgang Berghofer has predicted more top-level changes in East Germany, where Egon Krenz replaced Honocker as Communist Party chief last month.

On Thursday, the resignations of several East German officials were announced, including that of Honecker's wife, Margot. She had been education minister for 26 years.

Also Thursday, Annelis Kimmel became the first woman to head the federation of trade unions, replacing Honecker protege Harry Tisch.

Two regional party bosses quit after more than 20 years in their posts, and the leaders of two Communist-aligned parties resigned under pressure.

The Liberal Democrats, another Communist ally, called for the resignation of the entire 45-member Cabinet.

The Liberals have led a drive by non-Communist parties for more independence in recent weeks.

Despite the changes, tens of thousands of people again demonstrated for reforms in at least four cities late Thursday.

They marched in Gera, Erfurt, Halle and Wilhelm Pieck Stadt, the official ADN news agency reported.

It said marchers bearing candles and banners shouted through loud speakers for more democracy and an end to Communist Party privileges.

During recent weeks, tens of thousands have repeatedly taken to the streets for such protests.

Krenz, who replaced Honecker on Oct. 18, returned late Thursday from an afternoon visit to Warsaw, Poland. He met with non-Communist Prime Minister Tadeusz Mazowiecki and declared that East Germany could learn something from that country.